Becky McCall

Highly processed foods meet the same criteria as tobacco for addiction, and labeling them as such might benefit public health, according to a new U.S. study that proposes a set of criteria to assess the addictive potential of some foods.

The research suggests that health care professionals are taking steps toward framing food addiction as a clinical entity in its own right; it currently lacks validated treatment protocols and recognition as a clinical diagnosis.

Meanwhile, other data, reported by researchers at the 2022 Diabetes Professional Care conference in London also add support to the clinical recognition of food addiction.

Clinical psychologist Jen Unwin, PhD, from Southport, England, showed that a 3-month online program of low-carbohydrate diet together with psychoeducational support significantly reduced food addiction symptoms among a varied group of individuals, not all of whom were overweight or had obesity.

Dr. Unwin said her new data represent the first wide-scale clinical audit of its kind, other than a prior report of three patients with food addiction who were successfully treated with a ketogenic diet. 

“Food addiction explains so much of what we see in clinical practice, where intelligent people understand what we tell them about the physiology associated with a low-carb diet, and they follow it for a while, but then they relapse,” said Dr. Unwin, explaining the difficulties faced by around 20% of her patients who are considered to have food addiction.

Meanwhile, the authors of the U.S. study, led by Ashley N. Gearhardt, PhD, a psychologist from the University of Michigan, Ann Arbor, wrote that the ability of highly processed foods (HPFs) “to rapidly deliver high doses of refined carbohydrates and/or fat appear key to their addictive potential. Thus, we conclude that HPFs can be considered addictive substances based on scientifically established criteria.”

They asserted that the contribution to preventable deaths by a diet dominated by highly processed foods is comparable with that of tobacco products, and as such, like Dr. Unwin, the authors sought clinical recognition and a more formalized protocol to manage food addiction.

“Understanding whether addiction contributes to HPF intake may lead to new treatments, as preliminary research finds that behavioral and pharmacological interventions that target addictive mechanisms may reduce compulsive HPF intake,” they stated.

The study led by Dr. Gearhardt was published in the journal Addiction, and the study led by Unwin was also recently published in Frontiers in Psychiatry.
 

Addiction criteria similar to tobacco

HPFs can be associated with an eating phenotype “that reflects the hallmarks of addiction,” said Dr. Gearhardt and coauthors; typically, loss of control over intake, intense cravings, inability to cut down, and continued use despite negative consequences.

Acknowledging the lack of a single addictive agent, they explain that food addiction reflects mechanisms implicated in other addictive disorders such as smoking.

As such, in their study, Dr. Gearhardt and colleagues proposed a set of scientifically based criteria for the evaluation of whether certain foods are addictive. “Specifically, we propose the primary criteria used to resolve one of the last major controversies over whether a substance, tobacco products, was addictive.”

They consider certain foods according to the primary criteria that have stood the test of time after being proposed in 1988 by the U.S. Surgeon General to establish the addictive potential of tobacco: they trigger compulsive use, they have psychoactive effects, and they are reinforcing.

They have updated these criteria to include the ability to trigger urges and cravings, and added that “both these products [tobacco and HPFs] are legal, easily accessible, inexpensive, lack an intoxication syndrome, and are major causes of preventable death.”

For example, with compulsive use, tobacco meets this criterion because evidence suggests that most smokers would like to quit but are unable to do so.

Likewise, wrote Dr. Gearhardt and colleagues, even “in the face of significant diet-related health consequences (e.g., diabetes and cardiovascular disease), the majority of patients are unable to adhere to medically recommended dietary plans that require a reduction in HPF intake.”

Reinforcement, through tobacco use, is demonstrated by its ‘being sufficiently rewarding to maintain self-administration” because of its ability to deliver nicotine, they said, quoting the Surgeon General’s report, and likewise, with food addiction, “both adults and children will self-administer HPFs (e.g., potato chips, candy, and cookies) even when satiated.”
 

Online group food addiction intervention study

Dr. Unwin and coauthors want people with food addiction to be able to access a validated treatment protocol. Their study aimed to evaluate an online group intervention across multiple sites in the United States, Canada, and the United Kingdom, involving an abstinent, low-carbohydrate diet and biopsychosocial education focused on addiction and recovery in people self-identifying as having food addiction.

“Lots of people with food addiction go to GPs who don’t clinically recognize this, or if they attend addiction services and psychiatry, then they tend to only specialize in drugs, alcohol, and gambling. Eating disorder services are linked but their programs mostly don’t work for a food addict,” Dr. Unwin remarked in an interview.

“We feel running groups, as well as training professionals to run groups, is the best way to manage food addiction,” she said, reflecting on the scale of the problem, with around 10% of adults in the U.K. general population considered to have food addiction. In Dr. Unwin’s study, some people had type 2 diabetes and some overweight/obesity, but she added that some participants were underweight or of normal weight.

Initially, the 103 participants received weekly group (8-24 people) sessions for 10-14 weeks, and then monthly maintenance comprising follow-up that involved coaching participants on how to cope with relapse and get back on track.

Food addiction symptoms were assessed pre- and post program using the modified Yale Food Addiction Scale (mYFAS) 2.0; ICD-10 symptoms of food-related substance use disorder (CRAVED); and mental health well-being measured using the short version of the Warwick Edinburgh Mental Wellbeing scale and body weight.

“The program eliminates processed foods with a personalized, abstinence food plan that involves education around mechanisms involved,” said Dr. Unwin, who explained that processed foods deliver a dopamine high, and in response to this, the brain lowers the number of dopamine receptors to effectively counteract the increase in dopamine. This drop in dopamine receptors explains the depression often associated with food addiction.

Dr. Unwin reported that food addiction symptoms were significantly reduced, with the mYFAS dropping by 1.52, the CRAVED score by 1.53, and body weight by 2.34 kg (5.2 lb). Mental health, as measured by the Warwick Edinburgh Mental Wellbeing scale, improved by 2.37 points.

“We were very interested in mental health and well-being because it impacts so much across our lives, and we saw significant improvements here, but we were less interested in weight because food addicts come in all shapes and sizes with some people underweight,” said Dr. Unwin. “Food addiction symptoms were significantly improved in the group, but we now need to look at the longer-term outcomes.”

Dr. Unwin runs a low-carbohydrate program for type 2 diabetes with her husband David Unwin, MD, who is a GP in Southport, England. She said that they ask patients if they think they have food addiction, and most say they do.

“I always try to explain to patients about the dopamine high, and how this starts the craving which makes people wonder when and where they can find the next sugar hit. Just thinking about the next chocolate bar gets the dopamine running for many people, and the more they tread this path then the worse it gets because the dopamine receptors keep reducing.”

Lorraine Avery, RN, a diabetes nurse specialist for Solent NHS Trust, who attended the DPC conference, welcomed Dr. Unwin’s presentation.

“My concern as a diabetes nurse specialist is that I’m unsure all our patients recognize their food addiction, and there are often more drivers to eating than just the food in front of them,” she said in an interview. “I think there’s an emotional element, too. These people are often ‘yo-yo’ dieters, and they join lots of expert companies to help them lose weight, but these companies want them to regain and re-join their programs,” she said.

“I think there is something about helping patients recognize they have a food addiction and they need to consider that other approaches might be helpful.”

Dr. Unwin reported no relevant financial relationships; some other authors have fee-paying clients with food addiction. Dr. Gearhardt and Ms. Avery reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Highly processed foods meet the same criteria as tobacco for addiction, and labeling them as such might benefit public health, according to a new U.S. study that proposes a set of criteria to assess the addictive potential of some foods.

The research suggests that health care professionals are taking steps toward framing food addiction as a clinical entity in its own right; it currently lacks validated treatment protocols and recognition as a clinical diagnosis.

Meanwhile, other data, reported by researchers at the 2022 Diabetes Professional Care conference in London also add support to the clinical recognition of food addiction.

Clinical psychologist Jen Unwin, PhD, from Southport, England, showed that a 3-month online program of low-carbohydrate diet together with psychoeducational support significantly reduced food addiction symptoms among a varied group of individuals, not all of whom were overweight or had obesity.

Dr. Unwin said her new data represent the first wide-scale clinical audit of its kind, other than a prior report of three patients with food addiction who were successfully treated with a ketogenic diet. 

“Food addiction explains so much of what we see in clinical practice, where intelligent people understand what we tell them about the physiology associated with a low-carb diet, and they follow it for a while, but then they relapse,” said Dr. Unwin, explaining the difficulties faced by around 20% of her patients who are considered to have food addiction.

Meanwhile, the authors of the U.S. study, led by Ashley N. Gearhardt, PhD, a psychologist from the University of Michigan, Ann Arbor, wrote that the ability of highly processed foods (HPFs) “to rapidly deliver high doses of refined carbohydrates and/or fat appear key to their addictive potential. Thus, we conclude that HPFs can be considered addictive substances based on scientifically established criteria.”

They asserted that the contribution to preventable deaths by a diet dominated by highly processed foods is comparable with that of tobacco products, and as such, like Dr. Unwin, the authors sought clinical recognition and a more formalized protocol to manage food addiction.

“Understanding whether addiction contributes to HPF intake may lead to new treatments, as preliminary research finds that behavioral and pharmacological interventions that target addictive mechanisms may reduce compulsive HPF intake,” they stated.

The study led by Dr. Gearhardt was published in the journal Addiction, and the study led by Unwin was also recently published in Frontiers in Psychiatry.
 

Addiction criteria similar to tobacco

HPFs can be associated with an eating phenotype “that reflects the hallmarks of addiction,” said Dr. Gearhardt and coauthors; typically, loss of control over intake, intense cravings, inability to cut down, and continued use despite negative consequences.

Acknowledging the lack of a single addictive agent, they explain that food addiction reflects mechanisms implicated in other addictive disorders such as smoking.

As such, in their study, Dr. Gearhardt and colleagues proposed a set of scientifically based criteria for the evaluation of whether certain foods are addictive. “Specifically, we propose the primary criteria used to resolve one of the last major controversies over whether a substance, tobacco products, was addictive.”

They consider certain foods according to the primary criteria that have stood the test of time after being proposed in 1988 by the U.S. Surgeon General to establish the addictive potential of tobacco: they trigger compulsive use, they have psychoactive effects, and they are reinforcing.

They have updated these criteria to include the ability to trigger urges and cravings, and added that “both these products [tobacco and HPFs] are legal, easily accessible, inexpensive, lack an intoxication syndrome, and are major causes of preventable death.”

For example, with compulsive use, tobacco meets this criterion because evidence suggests that most smokers would like to quit but are unable to do so.

Likewise, wrote Dr. Gearhardt and colleagues, even “in the face of significant diet-related health consequences (e.g., diabetes and cardiovascular disease), the majority of patients are unable to adhere to medically recommended dietary plans that require a reduction in HPF intake.”

Reinforcement, through tobacco use, is demonstrated by its ‘being sufficiently rewarding to maintain self-administration” because of its ability to deliver nicotine, they said, quoting the Surgeon General’s report, and likewise, with food addiction, “both adults and children will self-administer HPFs (e.g., potato chips, candy, and cookies) even when satiated.”
 

Online group food addiction intervention study

Dr. Unwin and coauthors want people with food addiction to be able to access a validated treatment protocol. Their study aimed to evaluate an online group intervention across multiple sites in the United States, Canada, and the United Kingdom, involving an abstinent, low-carbohydrate diet and biopsychosocial education focused on addiction and recovery in people self-identifying as having food addiction.

“Lots of people with food addiction go to GPs who don’t clinically recognize this, or if they attend addiction services and psychiatry, then they tend to only specialize in drugs, alcohol, and gambling. Eating disorder services are linked but their programs mostly don’t work for a food addict,” Dr. Unwin remarked in an interview.

“We feel running groups, as well as training professionals to run groups, is the best way to manage food addiction,” she said, reflecting on the scale of the problem, with around 10% of adults in the U.K. general population considered to have food addiction. In Dr. Unwin’s study, some people had type 2 diabetes and some overweight/obesity, but she added that some participants were underweight or of normal weight.

Initially, the 103 participants received weekly group (8-24 people) sessions for 10-14 weeks, and then monthly maintenance comprising follow-up that involved coaching participants on how to cope with relapse and get back on track.

Food addiction symptoms were assessed pre- and post program using the modified Yale Food Addiction Scale (mYFAS) 2.0; ICD-10 symptoms of food-related substance use disorder (CRAVED); and mental health well-being measured using the short version of the Warwick Edinburgh Mental Wellbeing scale and body weight.

“The program eliminates processed foods with a personalized, abstinence food plan that involves education around mechanisms involved,” said Dr. Unwin, who explained that processed foods deliver a dopamine high, and in response to this, the brain lowers the number of dopamine receptors to effectively counteract the increase in dopamine. This drop in dopamine receptors explains the depression often associated with food addiction.

Dr. Unwin reported that food addiction symptoms were significantly reduced, with the mYFAS dropping by 1.52, the CRAVED score by 1.53, and body weight by 2.34 kg (5.2 lb). Mental health, as measured by the Warwick Edinburgh Mental Wellbeing scale, improved by 2.37 points.

“We were very interested in mental health and well-being because it impacts so much across our lives, and we saw significant improvements here, but we were less interested in weight because food addicts come in all shapes and sizes with some people underweight,” said Dr. Unwin. “Food addiction symptoms were significantly improved in the group, but we now need to look at the longer-term outcomes.”

Dr. Unwin runs a low-carbohydrate program for type 2 diabetes with her husband David Unwin, MD, who is a GP in Southport, England. She said that they ask patients if they think they have food addiction, and most say they do.

“I always try to explain to patients about the dopamine high, and how this starts the craving which makes people wonder when and where they can find the next sugar hit. Just thinking about the next chocolate bar gets the dopamine running for many people, and the more they tread this path then the worse it gets because the dopamine receptors keep reducing.”

Lorraine Avery, RN, a diabetes nurse specialist for Solent NHS Trust, who attended the DPC conference, welcomed Dr. Unwin’s presentation.

“My concern as a diabetes nurse specialist is that I’m unsure all our patients recognize their food addiction, and there are often more drivers to eating than just the food in front of them,” she said in an interview. “I think there’s an emotional element, too. These people are often ‘yo-yo’ dieters, and they join lots of expert companies to help them lose weight, but these companies want them to regain and re-join their programs,” she said.

“I think there is something about helping patients recognize they have a food addiction and they need to consider that other approaches might be helpful.”

Dr. Unwin reported no relevant financial relationships; some other authors have fee-paying clients with food addiction. Dr. Gearhardt and Ms. Avery reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Highly processed foods meet the same criteria as tobacco for addiction, and labeling them as such might benefit public health, according to a new U.S. study that proposes a set of criteria to assess the addictive potential of some foods.

The research suggests that health care professionals are taking steps toward framing food addiction as a clinical entity in its own right; it currently lacks validated treatment protocols and recognition as a clinical diagnosis.

Meanwhile, other data, reported by researchers at the 2022 Diabetes Professional Care conference in London also add support to the clinical recognition of food addiction.

Clinical psychologist Jen Unwin, PhD, from Southport, England, showed that a 3-month online program of low-carbohydrate diet together with psychoeducational support significantly reduced food addiction symptoms among a varied group of individuals, not all of whom were overweight or had obesity.

Dr. Unwin said her new data represent the first wide-scale clinical audit of its kind, other than a prior report of three patients with food addiction who were successfully treated with a ketogenic diet. 

“Food addiction explains so much of what we see in clinical practice, where intelligent people understand what we tell them about the physiology associated with a low-carb diet, and they follow it for a while, but then they relapse,” said Dr. Unwin, explaining the difficulties faced by around 20% of her patients who are considered to have food addiction.

Meanwhile, the authors of the U.S. study, led by Ashley N. Gearhardt, PhD, a psychologist from the University of Michigan, Ann Arbor, wrote that the ability of highly processed foods (HPFs) “to rapidly deliver high doses of refined carbohydrates and/or fat appear key to their addictive potential. Thus, we conclude that HPFs can be considered addictive substances based on scientifically established criteria.”

They asserted that the contribution to preventable deaths by a diet dominated by highly processed foods is comparable with that of tobacco products, and as such, like Dr. Unwin, the authors sought clinical recognition and a more formalized protocol to manage food addiction.

“Understanding whether addiction contributes to HPF intake may lead to new treatments, as preliminary research finds that behavioral and pharmacological interventions that target addictive mechanisms may reduce compulsive HPF intake,” they stated.

The study led by Dr. Gearhardt was published in the journal Addiction, and the study led by Unwin was also recently published in Frontiers in Psychiatry.
 

Addiction criteria similar to tobacco

HPFs can be associated with an eating phenotype “that reflects the hallmarks of addiction,” said Dr. Gearhardt and coauthors; typically, loss of control over intake, intense cravings, inability to cut down, and continued use despite negative consequences.

Acknowledging the lack of a single addictive agent, they explain that food addiction reflects mechanisms implicated in other addictive disorders such as smoking.

As such, in their study, Dr. Gearhardt and colleagues proposed a set of scientifically based criteria for the evaluation of whether certain foods are addictive. “Specifically, we propose the primary criteria used to resolve one of the last major controversies over whether a substance, tobacco products, was addictive.”

They consider certain foods according to the primary criteria that have stood the test of time after being proposed in 1988 by the U.S. Surgeon General to establish the addictive potential of tobacco: they trigger compulsive use, they have psychoactive effects, and they are reinforcing.

They have updated these criteria to include the ability to trigger urges and cravings, and added that “both these products [tobacco and HPFs] are legal, easily accessible, inexpensive, lack an intoxication syndrome, and are major causes of preventable death.”

For example, with compulsive use, tobacco meets this criterion because evidence suggests that most smokers would like to quit but are unable to do so.

Likewise, wrote Dr. Gearhardt and colleagues, even “in the face of significant diet-related health consequences (e.g., diabetes and cardiovascular disease), the majority of patients are unable to adhere to medically recommended dietary plans that require a reduction in HPF intake.”

Reinforcement, through tobacco use, is demonstrated by its ‘being sufficiently rewarding to maintain self-administration” because of its ability to deliver nicotine, they said, quoting the Surgeon General’s report, and likewise, with food addiction, “both adults and children will self-administer HPFs (e.g., potato chips, candy, and cookies) even when satiated.”
 

Online group food addiction intervention study

Dr. Unwin and coauthors want people with food addiction to be able to access a validated treatment protocol. Their study aimed to evaluate an online group intervention across multiple sites in the United States, Canada, and the United Kingdom, involving an abstinent, low-carbohydrate diet and biopsychosocial education focused on addiction and recovery in people self-identifying as having food addiction.

“Lots of people with food addiction go to GPs who don’t clinically recognize this, or if they attend addiction services and psychiatry, then they tend to only specialize in drugs, alcohol, and gambling. Eating disorder services are linked but their programs mostly don’t work for a food addict,” Dr. Unwin remarked in an interview.

“We feel running groups, as well as training professionals to run groups, is the best way to manage food addiction,” she said, reflecting on the scale of the problem, with around 10% of adults in the U.K. general population considered to have food addiction. In Dr. Unwin’s study, some people had type 2 diabetes and some overweight/obesity, but she added that some participants were underweight or of normal weight.

Initially, the 103 participants received weekly group (8-24 people) sessions for 10-14 weeks, and then monthly maintenance comprising follow-up that involved coaching participants on how to cope with relapse and get back on track.

Food addiction symptoms were assessed pre- and post program using the modified Yale Food Addiction Scale (mYFAS) 2.0; ICD-10 symptoms of food-related substance use disorder (CRAVED); and mental health well-being measured using the short version of the Warwick Edinburgh Mental Wellbeing scale and body weight.

“The program eliminates processed foods with a personalized, abstinence food plan that involves education around mechanisms involved,” said Dr. Unwin, who explained that processed foods deliver a dopamine high, and in response to this, the brain lowers the number of dopamine receptors to effectively counteract the increase in dopamine. This drop in dopamine receptors explains the depression often associated with food addiction.

Dr. Unwin reported that food addiction symptoms were significantly reduced, with the mYFAS dropping by 1.52, the CRAVED score by 1.53, and body weight by 2.34 kg (5.2 lb). Mental health, as measured by the Warwick Edinburgh Mental Wellbeing scale, improved by 2.37 points.

“We were very interested in mental health and well-being because it impacts so much across our lives, and we saw significant improvements here, but we were less interested in weight because food addicts come in all shapes and sizes with some people underweight,” said Dr. Unwin. “Food addiction symptoms were significantly improved in the group, but we now need to look at the longer-term outcomes.”

Dr. Unwin runs a low-carbohydrate program for type 2 diabetes with her husband David Unwin, MD, who is a GP in Southport, England. She said that they ask patients if they think they have food addiction, and most say they do.

“I always try to explain to patients about the dopamine high, and how this starts the craving which makes people wonder when and where they can find the next sugar hit. Just thinking about the next chocolate bar gets the dopamine running for many people, and the more they tread this path then the worse it gets because the dopamine receptors keep reducing.”

Lorraine Avery, RN, a diabetes nurse specialist for Solent NHS Trust, who attended the DPC conference, welcomed Dr. Unwin’s presentation.

“My concern as a diabetes nurse specialist is that I’m unsure all our patients recognize their food addiction, and there are often more drivers to eating than just the food in front of them,” she said in an interview. “I think there’s an emotional element, too. These people are often ‘yo-yo’ dieters, and they join lots of expert companies to help them lose weight, but these companies want them to regain and re-join their programs,” she said.

“I think there is something about helping patients recognize they have a food addiction and they need to consider that other approaches might be helpful.”

Dr. Unwin reported no relevant financial relationships; some other authors have fee-paying clients with food addiction. Dr. Gearhardt and Ms. Avery reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – Sexual dysfunction in patients with gastrointestinal disorders is undermanaged, with a lack of clinician education, time constraints, and embarrassment preventing constructive discussions to improve patient care and quality of life, according to a new survey.

Overall, 71% of gastroenterologists do not ask their patients about sexual dysfunction, the survey finds.

“While patients with gastrointestinal disorders often experience sexual dysfunction, discussions around the matter are not routine in gastroenterological care,” said Marco Romano, MD, from the University of Campania “Luigi Vanvitelli,” Naples, Italy.

Romano presented the survey findings at this year’s United European Gastroenterology Week meeting.

The research shows not only a clear need for better awareness but also a need to build gastroenterologists’ confidence in addressing sexual dysfunction with their patients, Dr. Romano added.

“Most felt that sexual medicine education and improvement of communication skills within the context of their residency training might be important in order to increase the awareness of sexual dysfunction, to overcome barriers, and to improve care and quality of life for their patients,” reported Dr. Romano. “This will lead to prompt diagnosis and treatment of any sexual problems.”

Respectfully asking the patients if their gastrointestinal disorders interfere with their intimate relationships “is often considered a relief to patients who find that the gastrointestinal problem and the sexual dysfunction are interlinked,” he added.
 

The findings

The survey was needed because the question of whether gastroenterologists inquire about their patients’ sexual issues had never been assessed, Dr. Romano said.

The researchers sent a cross-sectional, anonymous online survey to members of the Italian Society of Gastroenterology and Digestive Endoscopy. The questionnaire, designed and informed by a literature review, consisted of 29 single multiple-choice and open-ended questions.

A total of 426 surveys were returned: 335 from experienced gastroenterologists and 91 from residents (less experienced). Of all respondents, 54.7% were men and 45.3% were women.

Even though most gastroenterologists do not ask their patients about sexual dysfunction, the majority want to learn how to manage the issue, the survey found. Of the survey respondents, 80% agreed that it would be useful for gastroenterologists to attend courses dedicated to the problem of sexual dysfunction.

Only 4% of patients report (initiate a dialogue about) the problem, the survey found. Among women aged 40-50 years, the most common complaint reported was dyspareunia (pain on intercourse). In men, the most frequent complaints reported were in the over-40s age group, with 75% citing erectile dysfunction and 45% reporting loss of libido.

The most common gastrointestinal disorders associated with sexual dysfunction are inflammatory bowel diseases (37% of cases), chronic liver diseases (28%), and irritable bowel syndrome (26%), according to the survey.

On the question of whether medications played a role in patients’ sexual dysfunction, nearly 15% of respondents said that prokinetic agents were involved, and 18% thought proton pump inhibitors affect sexual function. Both drug classes are considered responsible for sexual disturbances.

Few gastroenterologists prescribe phosphodiesterase type 5 inhibitors (PDE5i), e.g., Viagra, to treat sexual dysfunction, the survey found. Approximately 90% of respondents said that they never prescribed this class of drugs, preferring to refer patients to an andrologist. Of those who did prescribe PDE5i, significantly fewer residents did compared with experienced gastroenterologists (1.1% vs. 8.8%, respectively; P = .01).

Finally, the biggest reasons why gastroenterologists do not discuss sexual dysfunction are lack of knowledge (80%), insufficient experience (58%), time (44%), and embarrassment (30%).
 

Practice experience matters

There were some differences among respondents in the experienced group vs. the residents. More men were in the experienced group compared with residents (57.6% vs. 44%, respectively); mean age was 47 years vs. 29 years, respectively; and 71% had 5 or more years of experience in the experienced gastroenterologist group, whereas 78% had 1-5 years of experience among residents.

The survey found that more residents than experienced gastroenterologists “never discussed sexual dysfunction” (38.5% vs. 21.3%, respectively; P = .001) and that more residents than experienced gastroenterologists reported that “patients did not relate their sexual dysfunction to the prescribed therapy” (47.8% vs. 32.5%, respectively; P = .007).

The two groups varied regarding prescription drugs’ role in sexual dysfunction. More experienced gastroenterologists than residents felt that proton pump inhibitors (5.8% vs. 0%, respectively; P = .018) or prokinetics (19.8% vs. 9.5%, respectively; P = .028) might be responsible for some degree of sexual dysfunction.

More residents than experienced doctors felt that other (nongastroenterologic) drugs might contribute to sexual dysfunction in their patients (57.1% vs. 44.7%, respectively; P = .043).

Dr. Romano reported that fewer residents than experienced gastroenterologists referred male patients with sexual dysfunction to an andrologist (frequently/always: 28.1% vs. 44.4%, respectively; P = .004). However, more residents than experienced gastroenterologists disagreed that discussing sexual dysfunction with patients pertains only to specialists (andrologists and gynecologists; 83.5% vs. 71.2%, respectively; P = .018).
 

Time to step up

Asma Fikree, BMBCh, PhD, of Royal London Hospital, Barts Health NHS Trust, London, moderated the session. The survey highlights that asking patients about sexual dysfunction is an area for improvement for gastroenterologists, she said.

“We might do it in men and ask about erectile dysfunction, but we are very poor about asking in women,” Dr. Fikree noted.

The pros and cons of different medications should be discussed with patients, she said.

Gastroenterologists need to do a better job of considering how medications can lead to sexual dysfunction and interfere with quality of life, and training would help, she added.

“Some patients might not be very bothered by sexual dysfunction, but others might consider it very important,” Dr. Fikree said. “We should be considering this as part of their treatment and care.”

Dr. Romano and Dr. Fikree report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – Sexual dysfunction in patients with gastrointestinal disorders is undermanaged, with a lack of clinician education, time constraints, and embarrassment preventing constructive discussions to improve patient care and quality of life, according to a new survey.

Overall, 71% of gastroenterologists do not ask their patients about sexual dysfunction, the survey finds.

“While patients with gastrointestinal disorders often experience sexual dysfunction, discussions around the matter are not routine in gastroenterological care,” said Marco Romano, MD, from the University of Campania “Luigi Vanvitelli,” Naples, Italy.

Romano presented the survey findings at this year’s United European Gastroenterology Week meeting.

The research shows not only a clear need for better awareness but also a need to build gastroenterologists’ confidence in addressing sexual dysfunction with their patients, Dr. Romano added.

“Most felt that sexual medicine education and improvement of communication skills within the context of their residency training might be important in order to increase the awareness of sexual dysfunction, to overcome barriers, and to improve care and quality of life for their patients,” reported Dr. Romano. “This will lead to prompt diagnosis and treatment of any sexual problems.”

Respectfully asking the patients if their gastrointestinal disorders interfere with their intimate relationships “is often considered a relief to patients who find that the gastrointestinal problem and the sexual dysfunction are interlinked,” he added.
 

The findings

The survey was needed because the question of whether gastroenterologists inquire about their patients’ sexual issues had never been assessed, Dr. Romano said.

The researchers sent a cross-sectional, anonymous online survey to members of the Italian Society of Gastroenterology and Digestive Endoscopy. The questionnaire, designed and informed by a literature review, consisted of 29 single multiple-choice and open-ended questions.

A total of 426 surveys were returned: 335 from experienced gastroenterologists and 91 from residents (less experienced). Of all respondents, 54.7% were men and 45.3% were women.

Even though most gastroenterologists do not ask their patients about sexual dysfunction, the majority want to learn how to manage the issue, the survey found. Of the survey respondents, 80% agreed that it would be useful for gastroenterologists to attend courses dedicated to the problem of sexual dysfunction.

Only 4% of patients report (initiate a dialogue about) the problem, the survey found. Among women aged 40-50 years, the most common complaint reported was dyspareunia (pain on intercourse). In men, the most frequent complaints reported were in the over-40s age group, with 75% citing erectile dysfunction and 45% reporting loss of libido.

The most common gastrointestinal disorders associated with sexual dysfunction are inflammatory bowel diseases (37% of cases), chronic liver diseases (28%), and irritable bowel syndrome (26%), according to the survey.

On the question of whether medications played a role in patients’ sexual dysfunction, nearly 15% of respondents said that prokinetic agents were involved, and 18% thought proton pump inhibitors affect sexual function. Both drug classes are considered responsible for sexual disturbances.

Few gastroenterologists prescribe phosphodiesterase type 5 inhibitors (PDE5i), e.g., Viagra, to treat sexual dysfunction, the survey found. Approximately 90% of respondents said that they never prescribed this class of drugs, preferring to refer patients to an andrologist. Of those who did prescribe PDE5i, significantly fewer residents did compared with experienced gastroenterologists (1.1% vs. 8.8%, respectively; P = .01).

Finally, the biggest reasons why gastroenterologists do not discuss sexual dysfunction are lack of knowledge (80%), insufficient experience (58%), time (44%), and embarrassment (30%).
 

Practice experience matters

There were some differences among respondents in the experienced group vs. the residents. More men were in the experienced group compared with residents (57.6% vs. 44%, respectively); mean age was 47 years vs. 29 years, respectively; and 71% had 5 or more years of experience in the experienced gastroenterologist group, whereas 78% had 1-5 years of experience among residents.

The survey found that more residents than experienced gastroenterologists “never discussed sexual dysfunction” (38.5% vs. 21.3%, respectively; P = .001) and that more residents than experienced gastroenterologists reported that “patients did not relate their sexual dysfunction to the prescribed therapy” (47.8% vs. 32.5%, respectively; P = .007).

The two groups varied regarding prescription drugs’ role in sexual dysfunction. More experienced gastroenterologists than residents felt that proton pump inhibitors (5.8% vs. 0%, respectively; P = .018) or prokinetics (19.8% vs. 9.5%, respectively; P = .028) might be responsible for some degree of sexual dysfunction.

More residents than experienced doctors felt that other (nongastroenterologic) drugs might contribute to sexual dysfunction in their patients (57.1% vs. 44.7%, respectively; P = .043).

Dr. Romano reported that fewer residents than experienced gastroenterologists referred male patients with sexual dysfunction to an andrologist (frequently/always: 28.1% vs. 44.4%, respectively; P = .004). However, more residents than experienced gastroenterologists disagreed that discussing sexual dysfunction with patients pertains only to specialists (andrologists and gynecologists; 83.5% vs. 71.2%, respectively; P = .018).
 

Time to step up

Asma Fikree, BMBCh, PhD, of Royal London Hospital, Barts Health NHS Trust, London, moderated the session. The survey highlights that asking patients about sexual dysfunction is an area for improvement for gastroenterologists, she said.

“We might do it in men and ask about erectile dysfunction, but we are very poor about asking in women,” Dr. Fikree noted.

The pros and cons of different medications should be discussed with patients, she said.

Gastroenterologists need to do a better job of considering how medications can lead to sexual dysfunction and interfere with quality of life, and training would help, she added.

“Some patients might not be very bothered by sexual dysfunction, but others might consider it very important,” Dr. Fikree said. “We should be considering this as part of their treatment and care.”

Dr. Romano and Dr. Fikree report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – Sexual dysfunction in patients with gastrointestinal disorders is undermanaged, with a lack of clinician education, time constraints, and embarrassment preventing constructive discussions to improve patient care and quality of life, according to a new survey.

Overall, 71% of gastroenterologists do not ask their patients about sexual dysfunction, the survey finds.

“While patients with gastrointestinal disorders often experience sexual dysfunction, discussions around the matter are not routine in gastroenterological care,” said Marco Romano, MD, from the University of Campania “Luigi Vanvitelli,” Naples, Italy.

Romano presented the survey findings at this year’s United European Gastroenterology Week meeting.

The research shows not only a clear need for better awareness but also a need to build gastroenterologists’ confidence in addressing sexual dysfunction with their patients, Dr. Romano added.

“Most felt that sexual medicine education and improvement of communication skills within the context of their residency training might be important in order to increase the awareness of sexual dysfunction, to overcome barriers, and to improve care and quality of life for their patients,” reported Dr. Romano. “This will lead to prompt diagnosis and treatment of any sexual problems.”

Respectfully asking the patients if their gastrointestinal disorders interfere with their intimate relationships “is often considered a relief to patients who find that the gastrointestinal problem and the sexual dysfunction are interlinked,” he added.
 

The findings

The survey was needed because the question of whether gastroenterologists inquire about their patients’ sexual issues had never been assessed, Dr. Romano said.

The researchers sent a cross-sectional, anonymous online survey to members of the Italian Society of Gastroenterology and Digestive Endoscopy. The questionnaire, designed and informed by a literature review, consisted of 29 single multiple-choice and open-ended questions.

A total of 426 surveys were returned: 335 from experienced gastroenterologists and 91 from residents (less experienced). Of all respondents, 54.7% were men and 45.3% were women.

Even though most gastroenterologists do not ask their patients about sexual dysfunction, the majority want to learn how to manage the issue, the survey found. Of the survey respondents, 80% agreed that it would be useful for gastroenterologists to attend courses dedicated to the problem of sexual dysfunction.

Only 4% of patients report (initiate a dialogue about) the problem, the survey found. Among women aged 40-50 years, the most common complaint reported was dyspareunia (pain on intercourse). In men, the most frequent complaints reported were in the over-40s age group, with 75% citing erectile dysfunction and 45% reporting loss of libido.

The most common gastrointestinal disorders associated with sexual dysfunction are inflammatory bowel diseases (37% of cases), chronic liver diseases (28%), and irritable bowel syndrome (26%), according to the survey.

On the question of whether medications played a role in patients’ sexual dysfunction, nearly 15% of respondents said that prokinetic agents were involved, and 18% thought proton pump inhibitors affect sexual function. Both drug classes are considered responsible for sexual disturbances.

Few gastroenterologists prescribe phosphodiesterase type 5 inhibitors (PDE5i), e.g., Viagra, to treat sexual dysfunction, the survey found. Approximately 90% of respondents said that they never prescribed this class of drugs, preferring to refer patients to an andrologist. Of those who did prescribe PDE5i, significantly fewer residents did compared with experienced gastroenterologists (1.1% vs. 8.8%, respectively; P = .01).

Finally, the biggest reasons why gastroenterologists do not discuss sexual dysfunction are lack of knowledge (80%), insufficient experience (58%), time (44%), and embarrassment (30%).
 

Practice experience matters

There were some differences among respondents in the experienced group vs. the residents. More men were in the experienced group compared with residents (57.6% vs. 44%, respectively); mean age was 47 years vs. 29 years, respectively; and 71% had 5 or more years of experience in the experienced gastroenterologist group, whereas 78% had 1-5 years of experience among residents.

The survey found that more residents than experienced gastroenterologists “never discussed sexual dysfunction” (38.5% vs. 21.3%, respectively; P = .001) and that more residents than experienced gastroenterologists reported that “patients did not relate their sexual dysfunction to the prescribed therapy” (47.8% vs. 32.5%, respectively; P = .007).

The two groups varied regarding prescription drugs’ role in sexual dysfunction. More experienced gastroenterologists than residents felt that proton pump inhibitors (5.8% vs. 0%, respectively; P = .018) or prokinetics (19.8% vs. 9.5%, respectively; P = .028) might be responsible for some degree of sexual dysfunction.

More residents than experienced doctors felt that other (nongastroenterologic) drugs might contribute to sexual dysfunction in their patients (57.1% vs. 44.7%, respectively; P = .043).

Dr. Romano reported that fewer residents than experienced gastroenterologists referred male patients with sexual dysfunction to an andrologist (frequently/always: 28.1% vs. 44.4%, respectively; P = .004). However, more residents than experienced gastroenterologists disagreed that discussing sexual dysfunction with patients pertains only to specialists (andrologists and gynecologists; 83.5% vs. 71.2%, respectively; P = .018).
 

Time to step up

Asma Fikree, BMBCh, PhD, of Royal London Hospital, Barts Health NHS Trust, London, moderated the session. The survey highlights that asking patients about sexual dysfunction is an area for improvement for gastroenterologists, she said.

“We might do it in men and ask about erectile dysfunction, but we are very poor about asking in women,” Dr. Fikree noted.

The pros and cons of different medications should be discussed with patients, she said.

Gastroenterologists need to do a better job of considering how medications can lead to sexual dysfunction and interfere with quality of life, and training would help, she added.

“Some patients might not be very bothered by sexual dysfunction, but others might consider it very important,” Dr. Fikree said. “We should be considering this as part of their treatment and care.”

Dr. Romano and Dr. Fikree report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), vs. it being administered into the large intestine, according to a new study.

Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.

“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.

Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.

“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.

“Until now, we’ve been targeting the wrong part of the intestine,” he said.

The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.

Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.

Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.

“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”

In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.

Targeting the small intestine

FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.

In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.

A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.

Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.

The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.

Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.

At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.

At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.

By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).

Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.

“Long-term side effects, as monitored up to 3 years, were not observed,” he added.

Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.

Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.

Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
 

Location affects bacterial success

Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.

Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.

“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”

“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
 

Broader questions

“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”

FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.

“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”

The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.

“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.

Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.

“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.

Drug distribution data are needed to determine host-microbiota interactions.

“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.

Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.

Through the AGA Center for Gut Microbiome Research and Education, AGA is committed to keeping you up-to-speed on the latest news, research and policy updates related to the gut microbiome: www.gastro.org/microbiome.  

A version of this article first appeared on Medscape.com.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), vs. it being administered into the large intestine, according to a new study.

Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.

“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.

Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.

“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.

“Until now, we’ve been targeting the wrong part of the intestine,” he said.

The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.

Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.

Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.

“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”

In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.

Targeting the small intestine

FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.

In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.

A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.

Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.

The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.

Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.

At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.

At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.

By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).

Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.

“Long-term side effects, as monitored up to 3 years, were not observed,” he added.

Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.

Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.

Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
 

Location affects bacterial success

Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.

Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.

“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”

“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
 

Broader questions

“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”

FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.

“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”

The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.

“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.

Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.

“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.

Drug distribution data are needed to determine host-microbiota interactions.

“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.

Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.

Through the AGA Center for Gut Microbiome Research and Education, AGA is committed to keeping you up-to-speed on the latest news, research and policy updates related to the gut microbiome: www.gastro.org/microbiome.  

A version of this article first appeared on Medscape.com.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), vs. it being administered into the large intestine, according to a new study.

Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.

“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.

Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.

“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.

“Until now, we’ve been targeting the wrong part of the intestine,” he said.

The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.

Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.

Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.

“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”

In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.

Targeting the small intestine

FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.

In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.

A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.

Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.

The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.

Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.

At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.

At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.

By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).

Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.

“Long-term side effects, as monitored up to 3 years, were not observed,” he added.

Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.

Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.

Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
 

Location affects bacterial success

Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.

Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.

“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”

“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
 

Broader questions

“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”

FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.

“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”

The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.

“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.

Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.

“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.

Drug distribution data are needed to determine host-microbiota interactions.

“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.

Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.

Through the AGA Center for Gut Microbiome Research and Education, AGA is committed to keeping you up-to-speed on the latest news, research and policy updates related to the gut microbiome: www.gastro.org/microbiome.  

A version of this article first appeared on Medscape.com.

VIENNA – The real-world risk of colorectal cancer and associated mortality was lower among people who underwent a single screening colonoscopy than among those who did not have a colonoscopy, though only modestly so, the 10-year follow-up of the large, multicenter, randomized Northern-European Initiative on Colorectal Cancer (NordICC) trial shows.

In effect, this means the number needed to invite to undergo screening to prevent one case of colorectal cancer is 455 (95% confidence interval, 270-1,429), the researchers determined.

The results were presented at the United European Gastroenterology Week 2022 meeting and were published simultaneously in The New England Journal of Medicine.

The results of the study, which was designed to be truly population based and to mimic national colorectal cancer screening programs, provide an estimate of the effect of screening colonoscopy in the general population.

The primary outcome was determined on an intention-to-screen basis. All persons who were invited to undergo colonoscopy screening were compared with people who received usual care (that is, received no invitation or screening). At UEG 2022, the researchers presented the interim 10-year colorectal cancer risk, which was found to be 0.98%, compared to 1.20%. This represents a risk reduction of 18% among colonoscopy invitees (risk ratio, 0.82; 95% CI, 0.70-0.93). During the study period, 259 cases of colorectal cancer were diagnosed in the invited group versus622 in the usual-care group.

The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (RR, 0.90; 95% CI, 0.64-1.16). The risk of death from any cause was similar in both the invited group and the usual-care group, at 11.03% and 11.04%, respectively (RR, 0.99; 95% CI, 0.96-1.04).

The authors noted that the benefit would have been greater had more people undergone screening; only 42% of those who were invited actually underwent colonoscopy. In an adjusted analysis, had all those who had been invited to undergo screening undergone colonoscopy, the 10-year risk of colorectal cancer would have decreased from 1.22% to 0.84%, and the risk of colorectal cancer–related death would have fallen from 0.30% to 0.15%.

The researchers, led by gastroenterologist Michael Bretthauer, MD, from the department of medicine, gastrointestinal endoscopy, University of Oslo, who presented the data at UEG 2022 on behalf of the NordICC study group, acknowledged that, despite the “observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer–related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned.”

However, they add that “optimism related to the effects of screening on colorectal cancer–related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses.”

With his coauthors, Dr. Bretthauer wrote that even their adjusted findings “probably underestimated the benefit because, as in most other large-scale trials of colorectal cancer screening, we could not adjust for all important confounders in all countries.”

Dr. Bretthauer also noted that results were similar to those achieved through sigmoidoscopy screening. By close comparison, sigmoidoscopy studies show the risk of colorectal cancer is reduced between 33% and 40%, according to per protocol analyses. “These results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy.”
 

Real-world, population-based study

NordICC is an ongoing, pragmatic study and is the first randomized trial to quantify the possible benefit of colonoscopy screening on risk of colorectal cancer and related death.

Researchers recruited healthy men and women from registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. Most participants came from Poland (54,258), followed by Norway (26,411) and Sweden (3,646). Data from the Netherlands could not be included owing to data protection law.

At baseline, 84,585 participants aged 55-64 years were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (28,220; invited) or to undergo usual care in each participant country (56,365; no invitation or screening).

Any colorectal cancer lesions detected were removed, whenever possible. The primary endpoints were the risks of colorectal cancer and colorectal cancer–related death. The secondary endpoint was death from any cause.
 

‘Modest effectiveness,’ but longer follow-up to give fuller picture

In an editorial that accompanied publication of the study, Jason A. Dominitz, MD, from the division of gastroenterology, University of Washington, Seattle, and Douglas J. Robertson, MD, from White River Junction (Vt.) Veterans Affairs Medical Center, commented on the possible reasons for the low reduction in incident cancer and deaths seen in NordICC.

They pointed out that cohort studies suggest a 40%-69% decrease in the incidence of colorectal cancer and a 29%-88% decrease in the risk of death with colonoscopy. However, they noted that “cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the inability to adjust for important factors such as incomplete adherence to testing and the tendency of healthier persons to seek preventive care.”

Referring to Dr. Bretthauer’s point about attendance to screening, Dr. Dominitz and Dr. Robertson added that, in the United States, colonoscopy is the predominant form of screening for colorectal cancer and that in countries where colonoscopy is less established, participation may be very different.

“The actual effectiveness of colonoscopy in populations that are more accepting of colonoscopy could more closely resemble the effectiveness shown in the per-protocol analysis in this trial,” they wrote.

The editorialists also pointed out that the benefits of screening colonoscopy take time to be realized “because the incidence of colorectal cancer is initially increased when presymptomatic cancers are identified.” A repeat and final analysis of the NordICC data is due at 15 years’ follow-up.

In addition, they noted that “colonoscopy is highly operator dependent” and that the adenoma detection rate is variable and affects cancer risk and related mortality.

Given the “modest effectiveness” of screening colonoscopy in the trial, they asserted that, “if the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and FIT [fecal immunochemical test]) are available.”

However, they also noted that “additional analyses, including longer follow up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test.”

Also commenting on the study was Michiel Maas, MD, from the department of gastroenterology and hepatology, Radboud UMC, Nijmegen, the Netherlands, told this news organization that he agreed that the absolute effect on colorectal cancer risk or colorectal cancer–related death was not as high as expected and may be disappointing.

But Dr. Maas said that “around half of the patients in the study did not undergo colonoscopy, which may have negatively impacted the results.

“An additional factor, which can be influential in colonoscopy studies, is the potential variability in detection rates between operators/endoscopists,” he said.

Looking to the future, Dr. Maas noted that “AI [artificial intelligence] or computer-aided detection can level this playing field in detection rates.

“Nevertheless, this is a very interesting study, which sheds a new light on the efficacy on screening colonoscopies,” he said.

Dr. Bretthauer has relationships with Paion, Cybernet, and the Norwegian Council of Research. Dr. Dominitz is cochair of VA Cooperative Studies Program #577: “Colonoscopy vs. Fecal Immunochemical Test (FIT) in Reducing Mortality from Colorectal Cancer” (the CONFIRM Study), which is funded by the Department of Veterans Affairs. Dr. Robertson is national cochair (with Dr. Dominitz) of the CONFIRM trial and has received personal fees from Freenome outside of the submitted work. Dr. Maas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – The real-world risk of colorectal cancer and associated mortality was lower among people who underwent a single screening colonoscopy than among those who did not have a colonoscopy, though only modestly so, the 10-year follow-up of the large, multicenter, randomized Northern-European Initiative on Colorectal Cancer (NordICC) trial shows.

In effect, this means the number needed to invite to undergo screening to prevent one case of colorectal cancer is 455 (95% confidence interval, 270-1,429), the researchers determined.

The results were presented at the United European Gastroenterology Week 2022 meeting and were published simultaneously in The New England Journal of Medicine.

The results of the study, which was designed to be truly population based and to mimic national colorectal cancer screening programs, provide an estimate of the effect of screening colonoscopy in the general population.

The primary outcome was determined on an intention-to-screen basis. All persons who were invited to undergo colonoscopy screening were compared with people who received usual care (that is, received no invitation or screening). At UEG 2022, the researchers presented the interim 10-year colorectal cancer risk, which was found to be 0.98%, compared to 1.20%. This represents a risk reduction of 18% among colonoscopy invitees (risk ratio, 0.82; 95% CI, 0.70-0.93). During the study period, 259 cases of colorectal cancer were diagnosed in the invited group versus622 in the usual-care group.

The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (RR, 0.90; 95% CI, 0.64-1.16). The risk of death from any cause was similar in both the invited group and the usual-care group, at 11.03% and 11.04%, respectively (RR, 0.99; 95% CI, 0.96-1.04).

The authors noted that the benefit would have been greater had more people undergone screening; only 42% of those who were invited actually underwent colonoscopy. In an adjusted analysis, had all those who had been invited to undergo screening undergone colonoscopy, the 10-year risk of colorectal cancer would have decreased from 1.22% to 0.84%, and the risk of colorectal cancer–related death would have fallen from 0.30% to 0.15%.

The researchers, led by gastroenterologist Michael Bretthauer, MD, from the department of medicine, gastrointestinal endoscopy, University of Oslo, who presented the data at UEG 2022 on behalf of the NordICC study group, acknowledged that, despite the “observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer–related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned.”

However, they add that “optimism related to the effects of screening on colorectal cancer–related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses.”

With his coauthors, Dr. Bretthauer wrote that even their adjusted findings “probably underestimated the benefit because, as in most other large-scale trials of colorectal cancer screening, we could not adjust for all important confounders in all countries.”

Dr. Bretthauer also noted that results were similar to those achieved through sigmoidoscopy screening. By close comparison, sigmoidoscopy studies show the risk of colorectal cancer is reduced between 33% and 40%, according to per protocol analyses. “These results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy.”
 

Real-world, population-based study

NordICC is an ongoing, pragmatic study and is the first randomized trial to quantify the possible benefit of colonoscopy screening on risk of colorectal cancer and related death.

Researchers recruited healthy men and women from registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. Most participants came from Poland (54,258), followed by Norway (26,411) and Sweden (3,646). Data from the Netherlands could not be included owing to data protection law.

At baseline, 84,585 participants aged 55-64 years were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (28,220; invited) or to undergo usual care in each participant country (56,365; no invitation or screening).

Any colorectal cancer lesions detected were removed, whenever possible. The primary endpoints were the risks of colorectal cancer and colorectal cancer–related death. The secondary endpoint was death from any cause.
 

‘Modest effectiveness,’ but longer follow-up to give fuller picture

In an editorial that accompanied publication of the study, Jason A. Dominitz, MD, from the division of gastroenterology, University of Washington, Seattle, and Douglas J. Robertson, MD, from White River Junction (Vt.) Veterans Affairs Medical Center, commented on the possible reasons for the low reduction in incident cancer and deaths seen in NordICC.

They pointed out that cohort studies suggest a 40%-69% decrease in the incidence of colorectal cancer and a 29%-88% decrease in the risk of death with colonoscopy. However, they noted that “cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the inability to adjust for important factors such as incomplete adherence to testing and the tendency of healthier persons to seek preventive care.”

Referring to Dr. Bretthauer’s point about attendance to screening, Dr. Dominitz and Dr. Robertson added that, in the United States, colonoscopy is the predominant form of screening for colorectal cancer and that in countries where colonoscopy is less established, participation may be very different.

“The actual effectiveness of colonoscopy in populations that are more accepting of colonoscopy could more closely resemble the effectiveness shown in the per-protocol analysis in this trial,” they wrote.

The editorialists also pointed out that the benefits of screening colonoscopy take time to be realized “because the incidence of colorectal cancer is initially increased when presymptomatic cancers are identified.” A repeat and final analysis of the NordICC data is due at 15 years’ follow-up.

In addition, they noted that “colonoscopy is highly operator dependent” and that the adenoma detection rate is variable and affects cancer risk and related mortality.

Given the “modest effectiveness” of screening colonoscopy in the trial, they asserted that, “if the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and FIT [fecal immunochemical test]) are available.”

However, they also noted that “additional analyses, including longer follow up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test.”

Also commenting on the study was Michiel Maas, MD, from the department of gastroenterology and hepatology, Radboud UMC, Nijmegen, the Netherlands, told this news organization that he agreed that the absolute effect on colorectal cancer risk or colorectal cancer–related death was not as high as expected and may be disappointing.

But Dr. Maas said that “around half of the patients in the study did not undergo colonoscopy, which may have negatively impacted the results.

“An additional factor, which can be influential in colonoscopy studies, is the potential variability in detection rates between operators/endoscopists,” he said.

Looking to the future, Dr. Maas noted that “AI [artificial intelligence] or computer-aided detection can level this playing field in detection rates.

“Nevertheless, this is a very interesting study, which sheds a new light on the efficacy on screening colonoscopies,” he said.

Dr. Bretthauer has relationships with Paion, Cybernet, and the Norwegian Council of Research. Dr. Dominitz is cochair of VA Cooperative Studies Program #577: “Colonoscopy vs. Fecal Immunochemical Test (FIT) in Reducing Mortality from Colorectal Cancer” (the CONFIRM Study), which is funded by the Department of Veterans Affairs. Dr. Robertson is national cochair (with Dr. Dominitz) of the CONFIRM trial and has received personal fees from Freenome outside of the submitted work. Dr. Maas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – The real-world risk of colorectal cancer and associated mortality was lower among people who underwent a single screening colonoscopy than among those who did not have a colonoscopy, though only modestly so, the 10-year follow-up of the large, multicenter, randomized Northern-European Initiative on Colorectal Cancer (NordICC) trial shows.

In effect, this means the number needed to invite to undergo screening to prevent one case of colorectal cancer is 455 (95% confidence interval, 270-1,429), the researchers determined.

The results were presented at the United European Gastroenterology Week 2022 meeting and were published simultaneously in The New England Journal of Medicine.

The results of the study, which was designed to be truly population based and to mimic national colorectal cancer screening programs, provide an estimate of the effect of screening colonoscopy in the general population.

The primary outcome was determined on an intention-to-screen basis. All persons who were invited to undergo colonoscopy screening were compared with people who received usual care (that is, received no invitation or screening). At UEG 2022, the researchers presented the interim 10-year colorectal cancer risk, which was found to be 0.98%, compared to 1.20%. This represents a risk reduction of 18% among colonoscopy invitees (risk ratio, 0.82; 95% CI, 0.70-0.93). During the study period, 259 cases of colorectal cancer were diagnosed in the invited group versus622 in the usual-care group.

The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (RR, 0.90; 95% CI, 0.64-1.16). The risk of death from any cause was similar in both the invited group and the usual-care group, at 11.03% and 11.04%, respectively (RR, 0.99; 95% CI, 0.96-1.04).

The authors noted that the benefit would have been greater had more people undergone screening; only 42% of those who were invited actually underwent colonoscopy. In an adjusted analysis, had all those who had been invited to undergo screening undergone colonoscopy, the 10-year risk of colorectal cancer would have decreased from 1.22% to 0.84%, and the risk of colorectal cancer–related death would have fallen from 0.30% to 0.15%.

The researchers, led by gastroenterologist Michael Bretthauer, MD, from the department of medicine, gastrointestinal endoscopy, University of Oslo, who presented the data at UEG 2022 on behalf of the NordICC study group, acknowledged that, despite the “observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer–related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned.”

However, they add that “optimism related to the effects of screening on colorectal cancer–related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses.”

With his coauthors, Dr. Bretthauer wrote that even their adjusted findings “probably underestimated the benefit because, as in most other large-scale trials of colorectal cancer screening, we could not adjust for all important confounders in all countries.”

Dr. Bretthauer also noted that results were similar to those achieved through sigmoidoscopy screening. By close comparison, sigmoidoscopy studies show the risk of colorectal cancer is reduced between 33% and 40%, according to per protocol analyses. “These results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy.”
 

Real-world, population-based study

NordICC is an ongoing, pragmatic study and is the first randomized trial to quantify the possible benefit of colonoscopy screening on risk of colorectal cancer and related death.

Researchers recruited healthy men and women from registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. Most participants came from Poland (54,258), followed by Norway (26,411) and Sweden (3,646). Data from the Netherlands could not be included owing to data protection law.

At baseline, 84,585 participants aged 55-64 years were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (28,220; invited) or to undergo usual care in each participant country (56,365; no invitation or screening).

Any colorectal cancer lesions detected were removed, whenever possible. The primary endpoints were the risks of colorectal cancer and colorectal cancer–related death. The secondary endpoint was death from any cause.
 

‘Modest effectiveness,’ but longer follow-up to give fuller picture

In an editorial that accompanied publication of the study, Jason A. Dominitz, MD, from the division of gastroenterology, University of Washington, Seattle, and Douglas J. Robertson, MD, from White River Junction (Vt.) Veterans Affairs Medical Center, commented on the possible reasons for the low reduction in incident cancer and deaths seen in NordICC.

They pointed out that cohort studies suggest a 40%-69% decrease in the incidence of colorectal cancer and a 29%-88% decrease in the risk of death with colonoscopy. However, they noted that “cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the inability to adjust for important factors such as incomplete adherence to testing and the tendency of healthier persons to seek preventive care.”

Referring to Dr. Bretthauer’s point about attendance to screening, Dr. Dominitz and Dr. Robertson added that, in the United States, colonoscopy is the predominant form of screening for colorectal cancer and that in countries where colonoscopy is less established, participation may be very different.

“The actual effectiveness of colonoscopy in populations that are more accepting of colonoscopy could more closely resemble the effectiveness shown in the per-protocol analysis in this trial,” they wrote.

The editorialists also pointed out that the benefits of screening colonoscopy take time to be realized “because the incidence of colorectal cancer is initially increased when presymptomatic cancers are identified.” A repeat and final analysis of the NordICC data is due at 15 years’ follow-up.

In addition, they noted that “colonoscopy is highly operator dependent” and that the adenoma detection rate is variable and affects cancer risk and related mortality.

Given the “modest effectiveness” of screening colonoscopy in the trial, they asserted that, “if the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and FIT [fecal immunochemical test]) are available.”

However, they also noted that “additional analyses, including longer follow up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test.”

Also commenting on the study was Michiel Maas, MD, from the department of gastroenterology and hepatology, Radboud UMC, Nijmegen, the Netherlands, told this news organization that he agreed that the absolute effect on colorectal cancer risk or colorectal cancer–related death was not as high as expected and may be disappointing.

But Dr. Maas said that “around half of the patients in the study did not undergo colonoscopy, which may have negatively impacted the results.

“An additional factor, which can be influential in colonoscopy studies, is the potential variability in detection rates between operators/endoscopists,” he said.

Looking to the future, Dr. Maas noted that “AI [artificial intelligence] or computer-aided detection can level this playing field in detection rates.

“Nevertheless, this is a very interesting study, which sheds a new light on the efficacy on screening colonoscopies,” he said.

Dr. Bretthauer has relationships with Paion, Cybernet, and the Norwegian Council of Research. Dr. Dominitz is cochair of VA Cooperative Studies Program #577: “Colonoscopy vs. Fecal Immunochemical Test (FIT) in Reducing Mortality from Colorectal Cancer” (the CONFIRM Study), which is funded by the Department of Veterans Affairs. Dr. Robertson is national cochair (with Dr. Dominitz) of the CONFIRM trial and has received personal fees from Freenome outside of the submitted work. Dr. Maas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), vs. it being administered into the large intestine, according to a new study.

Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.

“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.

Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.

“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.

“Until now, we’ve been targeting the wrong part of the intestine,” he said.

The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.

Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.

Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.

“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”

In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.
 

Targeting the small intestine

FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.

In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.

A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.

Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.

The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.

Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.

At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.

At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.

By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).

Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.

“Long-term side effects, as monitored up to 3 years, were not observed,” he added.

Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.

Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.

Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
 

Location affects bacterial success

Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.

Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.

“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”

“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
 

Broader questions

“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”

FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.

“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”

The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.

“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.

Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.

“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.

Drug distribution data are needed to determine host-microbiota interactions.

“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.

Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.

A version of this article first appeared on Medscape.com.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), vs. it being administered into the large intestine, according to a new study.

Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.

“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.

Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.

“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.

“Until now, we’ve been targeting the wrong part of the intestine,” he said.

The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.

Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.

Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.

“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”

In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.
 

Targeting the small intestine

FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.

In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.

A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.

Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.

The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.

Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.

At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.

At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.

By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).

Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.

“Long-term side effects, as monitored up to 3 years, were not observed,” he added.

Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.

Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.

Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
 

Location affects bacterial success

Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.

Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.

“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”

“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
 

Broader questions

“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”

FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.

“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”

The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.

“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.

Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.

“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.

Drug distribution data are needed to determine host-microbiota interactions.

“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.

Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.

A version of this article first appeared on Medscape.com.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), vs. it being administered into the large intestine, according to a new study.

Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.

“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.

Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.

“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.

“Until now, we’ve been targeting the wrong part of the intestine,” he said.

The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.

Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.

Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.

“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”

In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.
 

Targeting the small intestine

FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.

In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.

A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.

Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.

The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.

Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.

At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.

At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.

By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).

Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.

“Long-term side effects, as monitored up to 3 years, were not observed,” he added.

Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.

Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.

Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
 

Location affects bacterial success

Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.

Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.

“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”

“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
 

Broader questions

“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”

FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.

“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”

The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.

“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.

Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.

“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.

Drug distribution data are needed to determine host-microbiota interactions.

“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.

Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.

A version of this article first appeared on Medscape.com.

VIENNA – The real-world risk of colorectal cancer and associated mortality was lower among people who underwent a single screening colonoscopy than among those who did not have a colonoscopy, though only modestly so, the 10-year follow-up of the large, multicenter, randomized Northern-European Initiative on Colorectal Cancer (NordICC) trial shows.

In effect, this means the number needed to invite to undergo screening to prevent one case of colorectal cancer is 455 (95% confidence interval, 270-1,429), the researchers determined.

The results were presented at the United European Gastroenterology Week 2022 meeting and were published simultaneously in The New England Journal of Medicine.

The results of the study, which was designed to be truly population based and to mimic national colorectal cancer screening programs, provide an estimate of the effect of screening colonoscopy in the general population.

The primary outcome was determined on an intention-to-screen basis. All persons who were invited to undergo colonoscopy screening were compared with people who received usual care (that is, received no invitation or screening). At UEG 2022, the researchers presented the interim 10-year colorectal cancer risk, which was found to be 0.98%, compared to 1.20%. This represents a risk reduction of 18% among colonoscopy invitees (risk ratio, 0.82; 95% CI, 0.70-0.93). During the study period, 259 cases of colorectal cancer were diagnosed in the invited group versus622 in the usual-care group.

The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (RR, 0.90; 95% CI, 0.64-1.16). The risk of death from any cause was similar in both the invited group and the usual-care group, at 11.03% and 11.04%, respectively (RR, 0.99; 95% CI, 0.96-1.04).

The authors noted that the benefit would have been greater had more people undergone screening; only 42% of those who were invited actually underwent colonoscopy. In an adjusted analysis, had all those who had been invited to undergo screening undergone colonoscopy, the 10-year risk of colorectal cancer would have decreased from 1.22% to 0.84%, and the risk of colorectal cancer–related death would have fallen from 0.30% to 0.15%.

The researchers, led by gastroenterologist Michael Bretthauer, MD, from the department of medicine, gastrointestinal endoscopy, University of Oslo, who presented the data at UEG 2022 on behalf of the NordICC study group, acknowledged that, despite the “observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer–related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned.”

However, they add that “optimism related to the effects of screening on colorectal cancer–related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses.”

With his coauthors, Dr. Bretthauer wrote that even their adjusted findings “probably underestimated the benefit because, as in most other large-scale trials of colorectal cancer screening, we could not adjust for all important confounders in all countries.”

Dr. Bretthauer also noted that results were similar to those achieved through sigmoidoscopy screening. By close comparison, sigmoidoscopy studies show the risk of colorectal cancer is reduced between 33% and 40%, according to per protocol analyses. “These results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy.”
 

Real-world, population-based study

NordICC is an ongoing, pragmatic study and is the first randomized trial to quantify the possible benefit of colonoscopy screening on risk of colorectal cancer and related death.

Researchers recruited healthy men and women from registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. Most participants came from Poland (54,258), followed by Norway (26,411) and Sweden (3,646). Data from the Netherlands could not be included owing to data protection law.

At baseline, 84,585 participants aged 55-64 years were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (28,220; invited) or to undergo usual care in each participant country (56,365; no invitation or screening).

Any colorectal cancer lesions detected were removed, whenever possible. The primary endpoints were the risks of colorectal cancer and colorectal cancer–related death. The secondary endpoint was death from any cause.
 

‘Modest effectiveness,’ but longer follow-up to give fuller picture

In an editorial that accompanied publication of the study, Jason A. Dominitz, MD, from the division of gastroenterology, University of Washington, Seattle, and Douglas J. Robertson, MD, from White River Junction (Vt.) Veterans Affairs Medical Center, commented on the possible reasons for the low reduction in incident cancer and deaths seen in NordICC.

They pointed out that cohort studies suggest a 40%-69% decrease in the incidence of colorectal cancer and a 29%-88% decrease in the risk of death with colonoscopy. However, they noted that “cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the inability to adjust for important factors such as incomplete adherence to testing and the tendency of healthier persons to seek preventive care.”

Referring to Dr. Bretthauer’s point about attendance to screening, Dr. Dominitz and Dr. Robertson added that, in the United States, colonoscopy is the predominant form of screening for colorectal cancer and that in countries where colonoscopy is less established, participation may be very different.

“The actual effectiveness of colonoscopy in populations that are more accepting of colonoscopy could more closely resemble the effectiveness shown in the per-protocol analysis in this trial,” they wrote.

The editorialists also pointed out that the benefits of screening colonoscopy take time to be realized “because the incidence of colorectal cancer is initially increased when presymptomatic cancers are identified.” A repeat and final analysis of the NordICC data is due at 15 years’ follow-up.

In addition, they noted that “colonoscopy is highly operator dependent” and that the adenoma detection rate is variable and affects cancer risk and related mortality.

Given the “modest effectiveness” of screening colonoscopy in the trial, they asserted that, “if the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and FIT [fecal immunochemical test]) are available.”

However, they also noted that “additional analyses, including longer follow up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test.”

Also commenting on the study was Michiel Maas, MD, from the department of gastroenterology and hepatology, Radboud UMC, Nijmegen, the Netherlands, told this news organization that he agreed that the absolute effect on colorectal cancer risk or colorectal cancer–related death was not as high as expected and may be disappointing.

But Dr. Maas said that “around half of the patients in the study did not undergo colonoscopy, which may have negatively impacted the results.

“An additional factor, which can be influential in colonoscopy studies, is the potential variability in detection rates between operators/endoscopists,” he said.

Looking to the future, Dr. Maas noted that “AI [artificial intelligence] or computer-aided detection can level this playing field in detection rates.

“Nevertheless, this is a very interesting study, which sheds a new light on the efficacy on screening colonoscopies,” he said.

Dr. Bretthauer has relationships with Paion, Cybernet, and the Norwegian Council of Research. Dr. Dominitz is cochair of VA Cooperative Studies Program #577: “Colonoscopy vs. Fecal Immunochemical Test (FIT) in Reducing Mortality from Colorectal Cancer” (the CONFIRM Study), which is funded by the Department of Veterans Affairs. Dr. Robertson is national cochair (with Dr. Dominitz) of the CONFIRM trial and has received personal fees from Freenome outside of the submitted work. Dr. Maas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – The real-world risk of colorectal cancer and associated mortality was lower among people who underwent a single screening colonoscopy than among those who did not have a colonoscopy, though only modestly so, the 10-year follow-up of the large, multicenter, randomized Northern-European Initiative on Colorectal Cancer (NordICC) trial shows.

In effect, this means the number needed to invite to undergo screening to prevent one case of colorectal cancer is 455 (95% confidence interval, 270-1,429), the researchers determined.

The results were presented at the United European Gastroenterology Week 2022 meeting and were published simultaneously in The New England Journal of Medicine.

The results of the study, which was designed to be truly population based and to mimic national colorectal cancer screening programs, provide an estimate of the effect of screening colonoscopy in the general population.

The primary outcome was determined on an intention-to-screen basis. All persons who were invited to undergo colonoscopy screening were compared with people who received usual care (that is, received no invitation or screening). At UEG 2022, the researchers presented the interim 10-year colorectal cancer risk, which was found to be 0.98%, compared to 1.20%. This represents a risk reduction of 18% among colonoscopy invitees (risk ratio, 0.82; 95% CI, 0.70-0.93). During the study period, 259 cases of colorectal cancer were diagnosed in the invited group versus622 in the usual-care group.

The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (RR, 0.90; 95% CI, 0.64-1.16). The risk of death from any cause was similar in both the invited group and the usual-care group, at 11.03% and 11.04%, respectively (RR, 0.99; 95% CI, 0.96-1.04).

The authors noted that the benefit would have been greater had more people undergone screening; only 42% of those who were invited actually underwent colonoscopy. In an adjusted analysis, had all those who had been invited to undergo screening undergone colonoscopy, the 10-year risk of colorectal cancer would have decreased from 1.22% to 0.84%, and the risk of colorectal cancer–related death would have fallen from 0.30% to 0.15%.

The researchers, led by gastroenterologist Michael Bretthauer, MD, from the department of medicine, gastrointestinal endoscopy, University of Oslo, who presented the data at UEG 2022 on behalf of the NordICC study group, acknowledged that, despite the “observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer–related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned.”

However, they add that “optimism related to the effects of screening on colorectal cancer–related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses.”

With his coauthors, Dr. Bretthauer wrote that even their adjusted findings “probably underestimated the benefit because, as in most other large-scale trials of colorectal cancer screening, we could not adjust for all important confounders in all countries.”

Dr. Bretthauer also noted that results were similar to those achieved through sigmoidoscopy screening. By close comparison, sigmoidoscopy studies show the risk of colorectal cancer is reduced between 33% and 40%, according to per protocol analyses. “These results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy.”
 

Real-world, population-based study

NordICC is an ongoing, pragmatic study and is the first randomized trial to quantify the possible benefit of colonoscopy screening on risk of colorectal cancer and related death.

Researchers recruited healthy men and women from registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. Most participants came from Poland (54,258), followed by Norway (26,411) and Sweden (3,646). Data from the Netherlands could not be included owing to data protection law.

At baseline, 84,585 participants aged 55-64 years were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (28,220; invited) or to undergo usual care in each participant country (56,365; no invitation or screening).

Any colorectal cancer lesions detected were removed, whenever possible. The primary endpoints were the risks of colorectal cancer and colorectal cancer–related death. The secondary endpoint was death from any cause.
 

‘Modest effectiveness,’ but longer follow-up to give fuller picture

In an editorial that accompanied publication of the study, Jason A. Dominitz, MD, from the division of gastroenterology, University of Washington, Seattle, and Douglas J. Robertson, MD, from White River Junction (Vt.) Veterans Affairs Medical Center, commented on the possible reasons for the low reduction in incident cancer and deaths seen in NordICC.

They pointed out that cohort studies suggest a 40%-69% decrease in the incidence of colorectal cancer and a 29%-88% decrease in the risk of death with colonoscopy. However, they noted that “cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the inability to adjust for important factors such as incomplete adherence to testing and the tendency of healthier persons to seek preventive care.”

Referring to Dr. Bretthauer’s point about attendance to screening, Dr. Dominitz and Dr. Robertson added that, in the United States, colonoscopy is the predominant form of screening for colorectal cancer and that in countries where colonoscopy is less established, participation may be very different.

“The actual effectiveness of colonoscopy in populations that are more accepting of colonoscopy could more closely resemble the effectiveness shown in the per-protocol analysis in this trial,” they wrote.

The editorialists also pointed out that the benefits of screening colonoscopy take time to be realized “because the incidence of colorectal cancer is initially increased when presymptomatic cancers are identified.” A repeat and final analysis of the NordICC data is due at 15 years’ follow-up.

In addition, they noted that “colonoscopy is highly operator dependent” and that the adenoma detection rate is variable and affects cancer risk and related mortality.

Given the “modest effectiveness” of screening colonoscopy in the trial, they asserted that, “if the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and FIT [fecal immunochemical test]) are available.”

However, they also noted that “additional analyses, including longer follow up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test.”

Also commenting on the study was Michiel Maas, MD, from the department of gastroenterology and hepatology, Radboud UMC, Nijmegen, the Netherlands, told this news organization that he agreed that the absolute effect on colorectal cancer risk or colorectal cancer–related death was not as high as expected and may be disappointing.

But Dr. Maas said that “around half of the patients in the study did not undergo colonoscopy, which may have negatively impacted the results.

“An additional factor, which can be influential in colonoscopy studies, is the potential variability in detection rates between operators/endoscopists,” he said.

Looking to the future, Dr. Maas noted that “AI [artificial intelligence] or computer-aided detection can level this playing field in detection rates.

“Nevertheless, this is a very interesting study, which sheds a new light on the efficacy on screening colonoscopies,” he said.

Dr. Bretthauer has relationships with Paion, Cybernet, and the Norwegian Council of Research. Dr. Dominitz is cochair of VA Cooperative Studies Program #577: “Colonoscopy vs. Fecal Immunochemical Test (FIT) in Reducing Mortality from Colorectal Cancer” (the CONFIRM Study), which is funded by the Department of Veterans Affairs. Dr. Robertson is national cochair (with Dr. Dominitz) of the CONFIRM trial and has received personal fees from Freenome outside of the submitted work. Dr. Maas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VIENNA – The real-world risk of colorectal cancer and associated mortality was lower among people who underwent a single screening colonoscopy than among those who did not have a colonoscopy, though only modestly so, the 10-year follow-up of the large, multicenter, randomized Northern-European Initiative on Colorectal Cancer (NordICC) trial shows.

In effect, this means the number needed to invite to undergo screening to prevent one case of colorectal cancer is 455 (95% confidence interval, 270-1,429), the researchers determined.

The results were presented at the United European Gastroenterology Week 2022 meeting and were published simultaneously in The New England Journal of Medicine.

The results of the study, which was designed to be truly population based and to mimic national colorectal cancer screening programs, provide an estimate of the effect of screening colonoscopy in the general population.

The primary outcome was determined on an intention-to-screen basis. All persons who were invited to undergo colonoscopy screening were compared with people who received usual care (that is, received no invitation or screening). At UEG 2022, the researchers presented the interim 10-year colorectal cancer risk, which was found to be 0.98%, compared to 1.20%. This represents a risk reduction of 18% among colonoscopy invitees (risk ratio, 0.82; 95% CI, 0.70-0.93). During the study period, 259 cases of colorectal cancer were diagnosed in the invited group versus622 in the usual-care group.

The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (RR, 0.90; 95% CI, 0.64-1.16). The risk of death from any cause was similar in both the invited group and the usual-care group, at 11.03% and 11.04%, respectively (RR, 0.99; 95% CI, 0.96-1.04).

The authors noted that the benefit would have been greater had more people undergone screening; only 42% of those who were invited actually underwent colonoscopy. In an adjusted analysis, had all those who had been invited to undergo screening undergone colonoscopy, the 10-year risk of colorectal cancer would have decreased from 1.22% to 0.84%, and the risk of colorectal cancer–related death would have fallen from 0.30% to 0.15%.

The researchers, led by gastroenterologist Michael Bretthauer, MD, from the department of medicine, gastrointestinal endoscopy, University of Oslo, who presented the data at UEG 2022 on behalf of the NordICC study group, acknowledged that, despite the “observed appreciable reductions in relative risks, the absolute risks of the risk of colorectal cancer and even more so of colorectal cancer–related death were lower than those in previous screening trials and lower than what we anticipated when the trial was planned.”

However, they add that “optimism related to the effects of screening on colorectal cancer–related death may be warranted in light of the 50% decrease observed in adjusted per-protocol analyses.”

With his coauthors, Dr. Bretthauer wrote that even their adjusted findings “probably underestimated the benefit because, as in most other large-scale trials of colorectal cancer screening, we could not adjust for all important confounders in all countries.”

Dr. Bretthauer also noted that results were similar to those achieved through sigmoidoscopy screening. By close comparison, sigmoidoscopy studies show the risk of colorectal cancer is reduced between 33% and 40%, according to per protocol analyses. “These results suggest that colonoscopy screening might not be substantially better in reducing the risk of colorectal cancer than sigmoidoscopy.”
 

Real-world, population-based study

NordICC is an ongoing, pragmatic study and is the first randomized trial to quantify the possible benefit of colonoscopy screening on risk of colorectal cancer and related death.

Researchers recruited healthy men and women from registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. Most participants came from Poland (54,258), followed by Norway (26,411) and Sweden (3,646). Data from the Netherlands could not be included owing to data protection law.

At baseline, 84,585 participants aged 55-64 years were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (28,220; invited) or to undergo usual care in each participant country (56,365; no invitation or screening).

Any colorectal cancer lesions detected were removed, whenever possible. The primary endpoints were the risks of colorectal cancer and colorectal cancer–related death. The secondary endpoint was death from any cause.
 

‘Modest effectiveness,’ but longer follow-up to give fuller picture

In an editorial that accompanied publication of the study, Jason A. Dominitz, MD, from the division of gastroenterology, University of Washington, Seattle, and Douglas J. Robertson, MD, from White River Junction (Vt.) Veterans Affairs Medical Center, commented on the possible reasons for the low reduction in incident cancer and deaths seen in NordICC.

They pointed out that cohort studies suggest a 40%-69% decrease in the incidence of colorectal cancer and a 29%-88% decrease in the risk of death with colonoscopy. However, they noted that “cohort studies probably overestimate the real-world effectiveness of colonoscopy because of the inability to adjust for important factors such as incomplete adherence to testing and the tendency of healthier persons to seek preventive care.”

Referring to Dr. Bretthauer’s point about attendance to screening, Dr. Dominitz and Dr. Robertson added that, in the United States, colonoscopy is the predominant form of screening for colorectal cancer and that in countries where colonoscopy is less established, participation may be very different.

“The actual effectiveness of colonoscopy in populations that are more accepting of colonoscopy could more closely resemble the effectiveness shown in the per-protocol analysis in this trial,” they wrote.

The editorialists also pointed out that the benefits of screening colonoscopy take time to be realized “because the incidence of colorectal cancer is initially increased when presymptomatic cancers are identified.” A repeat and final analysis of the NordICC data is due at 15 years’ follow-up.

In addition, they noted that “colonoscopy is highly operator dependent” and that the adenoma detection rate is variable and affects cancer risk and related mortality.

Given the “modest effectiveness” of screening colonoscopy in the trial, they asserted that, “if the trial truly represents the real-world performance of population-based screening colonoscopy, it might be hard to justify the risk and expense of this form of screening when simpler, less-invasive strategies (e.g., sigmoidoscopy and FIT [fecal immunochemical test]) are available.”

However, they also noted that “additional analyses, including longer follow up and results from other ongoing comparative effectiveness trials, will help us to fully understand the benefits of this test.”

Also commenting on the study was Michiel Maas, MD, from the department of gastroenterology and hepatology, Radboud UMC, Nijmegen, the Netherlands, told this news organization that he agreed that the absolute effect on colorectal cancer risk or colorectal cancer–related death was not as high as expected and may be disappointing.

But Dr. Maas said that “around half of the patients in the study did not undergo colonoscopy, which may have negatively impacted the results.

“An additional factor, which can be influential in colonoscopy studies, is the potential variability in detection rates between operators/endoscopists,” he said.

Looking to the future, Dr. Maas noted that “AI [artificial intelligence] or computer-aided detection can level this playing field in detection rates.

“Nevertheless, this is a very interesting study, which sheds a new light on the efficacy on screening colonoscopies,” he said.

Dr. Bretthauer has relationships with Paion, Cybernet, and the Norwegian Council of Research. Dr. Dominitz is cochair of VA Cooperative Studies Program #577: “Colonoscopy vs. Fecal Immunochemical Test (FIT) in Reducing Mortality from Colorectal Cancer” (the CONFIRM Study), which is funded by the Department of Veterans Affairs. Dr. Robertson is national cochair (with Dr. Dominitz) of the CONFIRM trial and has received personal fees from Freenome outside of the submitted work. Dr. Maas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – It remains inconclusive whether SARS-CoV-2 infection predisposes children and adolescents to a higher risk of type 1 diabetes. Data from two new studies and a recently published research letter add to the growing body of knowledge on the subject, but still can’t draw any definitive conclusions.

The latest results from a Norwegian and a Scottish study both examine incidence of type 1 diabetes in young people with a history of SARS-CoV-2 infection and were reported at the annual meeting of the European Association for the Study of Diabetes.

A 60% increased risk for type 1 diabetes at least 31 days after SARS-CoV-2 infection (adjusted hazard ratio, 1.63) was found in the Norwegian study, while in contrast, the Scottish study only found an increased risk in the first few months of the pandemic, in 2020, but importantly, no association over a much longer time period (March 2020–November 2021).

In a comment on Twitter on the two studies presented at EASD, session moderator Kamlesh Khunti, MD, professor of primary care diabetes and vascular medicine at the University of Leicester, (England), said: “In summary, two studies showing no or weak association of type 1 diabetes with COVID.”

But new data in the research letter published in JAMA Network Open, based on U.S. figures, also found an almost doubling of type 1 diabetes in children in the first few months after COVID-19 infection relative to infection with other respiratory viruses.

Lead author of the Scottish study, Helen Colhoun, PhD, honorary public health consultant at Public Health Scotland, commented: “Data in children are variable year on year, which emphasizes the need to be cautious over taking a tiny snapshot.”

Nevertheless, this is “a hugely important question and we must not drop the ball. [We must] keep looking at it and maintain scientific equipoise. ... [This] reinforces the need to carry on this analysis into the future to obtain an unequivocal picture,” she emphasized.
 

Norwegian study: If there is an association, the risk is small

German Tapia, PhD, from the Norwegian Institute of Public Health, Oslo, presented the results of a study of SARS-CoV-2 infection and subsequent risk of type 1 diabetes in 1.2 million children in Norway.

Of these, 424,354 children had been infected with SARS-CoV-2, and there were 990 incident cases of type 1 diabetes.

“What we do know about COVID-19 in children is that the symptoms are mild and only a small proportion are hospitalized with more serious symptoms. But we do not know the long-term effects of COVID-19 infection because this requires a longer follow-up period,” remarked Dr. Tapia, adding that other viral infections are thought to be linked to the development of type 1 diabetes, in particular, respiratory infections.

The data were sourced from the Norwegian Emergency Preparedness Register for COVID-19, which gathers daily data updates including infections (positive and negative results for free-of-charge testing), diagnoses (primary and secondary care), vaccinations (also free of charge), prescribed medications, and basic demographics.

“We link these data using the personal identification number that every Norwegian citizen has,” explained Dr. Tapia.

He presented results from two cohorts: firstly, results in children only, including those tested for SARS-CoV-2 infection, and secondly, a full national Norwegian population cohort.

Regarding the first cohort, those under 18 years who tested positive for SARS-CoV-2 infection, from March 2020 to March 2022, had a significantly increased risk of type 1 diabetes at least 31 days after infection, with an adjusted hazard ratio of 1.63 (95% confidence interval, 1.08-2.47; P = .02). Adjustments were made for age, sex, non-Nordic country of origin, geographic area, and socioeconomic factors.

For children who developed type 1 diabetes within 30 days of a SARS-CoV-2 infection, the HR was 1.26 (95% CI, 0.72-2.19; P = .42), which did not reach statistical significance.

“The fact that fewer people developed type 1 diabetes within 30 days is not surprising because we know that type 1 diabetes develops over a long period of time,” Dr. Tapia said.

“For this reason, we would not expect to find new cases of those people who develop type 1 diabetes within 30 days of COVID-19 infection,” he explained. In these cases, “it is most likely that they already had [type 1 diabetes], and the infection probably triggered clinical symptoms, so their type 1 diabetes was discovered.”

Turning to the full population cohort and diagnoses of type 1 diabetes over 30 days after SARS-CoV-2 infection, the Norwegian researchers found an association, with an HR of 1.57 (95% CI, 1.06-2.33; P = .03), while diagnosis of type 1 diabetes at 30 days or less generated a hazard ratio of 1.22 (95% CI, 0.72-2.19; P = .42).

“So very similar results were found, and after adjustment for confounders, results were still similar,” reported Dr. Tapia.

He also conducted a similar analysis with vaccination as an exposure but found no association between vaccination against SARS-CoV-2 and diagnosis of type 1 diabetes.

“From these results, we conclude that this suggests an increase in diagnosis of type 1 diabetes after SARS-CoV-2 infection, but it must be noted that the absolute risk of developing type 1 diabetes after infection in children is low, with most children not developing the disease,” he emphasized. “There are nearly half a million children who have been infected with SARS-CoV-2 in Norway, but only a very small proportion develop type 1 diabetes.”
 

Scottish study: No association found over longer term

Dr. Colhoun and colleagues looked at the relationship between incident type 1 diabetes and SARS-CoV-2 infection in children in Scotland using e-health record linkage.

The study involved 1.8 million people under 35 years of age and found very weak, if any, evidence of an association between incident type 1 diabetes and SARS-CoV-2.

Examining data between March 2020 and November 2021, Dr. Colhoun and colleagues identified 365,080 individuals up to age 35 with at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes.

“In children under 16 years, suspected cases of type 1 diabetes are admitted to hospital, and 97% of diagnosis dates are recorded in the Scottish Care Information – Diabetes Collaboration register [SCI-Diabetes] prior to or within 2 days of the first hospital admission for type 1 diabetes,” Dr. Colhoun said, stressing the timeliness of the data.

“We found the incidence of type 1 diabetes diagnosis increased 1.2-fold in those aged 0-14 years, but we did not find any association at an individual level of COVID-19 infection over 30 days prior to a type 1 diabetes diagnosis, in this particular dataset,” she reported. In young people aged 15-34, there was a linear increase in incident type 1 diabetes from 2015 to 2021 with no pandemic increase.

Referring to the 1.2-fold increase soon after the pandemic started, she explained that, in 0- to 14-year-olds, the increase followed a drop in the preceding months prepandemic in 2019. They also found that the seasonal pattern of type 1 diabetes diagnoses remained roughly the same across the pandemic months, with typical peaks in February and September.

In the cohort of under 35s, researchers also found a rate ratio of 2.62 (95% CI, 1.81-3.78) within a 30-day window of SARS-CoV-2 infection, but beyond 30 days, no evidence was seen of an association, with a RR of 0.86 (95% CI, 0.62-1.21; P = .40), she reported.

She explained her reasons for not considering diagnoses within 30 days of COVID-19 as causative. Echoing Dr. Tapia, Dr. Colhoun said the median time from symptom onset to diagnosis of type 1 diabetes is 25 days. “This suggests that 50% have had symptoms for over 25 days at diagnosis.”

She also stressed that when they compared the timing of SARS-CoV-2 testing with diagnosis, they found a much higher rate of COVID-19 testing around diagnosis. “This was not least because everyone admitted to hospital had to have a COVID-19 test.”
 

Latest U.S. data point to a link

Meanwhile, for the new data reported in JAMA Network Open, medical student Ellen K. Kendall of Case Western Reserve University, Cleveland, matched 571,256 pediatric patients: 285,628 with COVID-19 and 285,628 with non–COVID-19 respiratory infections.

By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of type 1 diabetes, but only 72 (0.025%) were diagnosed with type 1 diabetes within 6 months after non–COVID-19 respiratory infection.

At 1, 3, and 6 months after infection, risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2, compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96; 3 months: HR, 2.10; and 6 months: HR, 1.83), and in subgroups of patients aged 0-9 years, a group unlikely to develop type 2 diabetes.

“In this study, new type 1 diabetes diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems),” noted Ms. Kendall and coauthors. “Respiratory infections have previously been associated with onset of type 1 diabetes, but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths.”

“The increased risk of new-onset type 1 diabetes after COVID-19 adds an important consideration for risk–benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A study from the Centers for Disease Control and Prevention published in January 2022, also concluded there was a link between COVID-19 and diabetes in children, but not with other acute respiratory infections. Children were 2.5 times more likely to be diagnosed with diabetes following a SARS-CoV-2 infection, it found.

However, the study has been criticized because it pooled all types of diabetes together and did not account for other health conditions, medications that can increase blood glucose levels, race, obesity, and other social determinants of health that might influence a child’s risk of acquiring COVID-19 or diabetes.

“I’ve no doubt that the CDC data were incorrect because the incidence rate for ... diabetes, even in those never exposed to COVID-19 infection, was 10 times the rate ever reported in the U.S.,” Dr. Colhoun said. “There’s no way these data are correct. I believe there was a confusion between incidence and prevalence of diabetes.”

“This paper caused a great deal of panic, especially among those who have a child with type 1diabetes, so we need to be very careful not to cause undue alarm until we have more definitive evidence in this arena,” she stressed.

However, she also acknowledged that the new Norwegian study was well conducted, and she has no methodological concerns about it, so “I think we just have to wait and see.”

Given the inconclusiveness on the issue, there is an ongoing CoviDiab registry collecting data on this very subject.

Dr. Tapia presented on behalf of lead author Dr. Gulseth, who has reported no relevant financial relationships. Dr. Colhoun also reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Shivering upon repeated short exposures to cold improves glucose tolerance, decreases fasting blood glucose and lipid levels, and markedly reduces blood pressure, show new study results in adults with obesity and overweight.

Presenting the preliminary findings at the annual meeting of the European Association for the Study of Diabetes, Adam Sellers, a PhD student from Maastricht (the Netherlands) University, said: “The results are highly promising and may eventually suggest an alternative treatment or preventative measure for type 2 diabetes.”

Dr. Sellers found that 10 daily 1-hour sessions of shivering at 10° C led to 85% of participants showing a drop in fasting glucose, and a 32% drop in lipid levels, as well as a blood pressure drop of around 8% overall.

Although cold exposure is known to increase brown fat, Dr. Sellers doesn’t believe this explains his findings. “This research, in addition to two other prior studies, suggest that shivering and skeletal muscle may play a more important role than brown fat,” he said.

“Muscle can contract mechanically – [the concept of the] shivers – thereby generating heat, and there is considerably more muscle than brown fat in a human, so shivering can burn more calories and produce more heat,” he explained.

He added that, in the future, “in a similar way to saunas and steam rooms, there might be cold rooms where people go and sit in the cold room and shiver, or possibly patients attend hospital and shivering is induced.”

Audience member Anna Krook, PhD, professor of integrative physiology at the Karolinska Institute, Stockholm, commented on the work, saying the results are “potent” and demonstrate the metabolic effect of shivering. “One thing that struck me was, given the time the subject had to spend – 1 hour shivering over 10 days, I wonder if 1 hour of exercise would show similarly potent effects, and perhaps for those people who cannot perform exercise for whatever reason this might be a good alternative.”

She pointed out that, in terms of translation into practice, it “really depends on how tolerable this is. It also shows how important our muscle is in regulating metabolism. The study showed that you had to be shivering, and it wasn’t just enough to be cold, which has implications for the role of brown fat, especially when we consider the small amount of brown fat we have compared to muscle, which can be half of body weight.”

And Denis P. Blondin, PhD, said: “The reality is that we know it can be difficult and even painful for individuals with obesity to perform exercise, and therefore, cold exposure offers a passive way of improving our metabolic profile and cardiovascular health.”

“Some will argue that it is unrealistic to propose cold exposure as a therapy, but people overlook the fact that cold exposure [mostly through cold-water immersion] has increased in popularity over the past 5 years and has also been a cultural staple for many Nordic countries, albeit often performed with heat exposure as well [see the use of saunas and cold-water swimming in Finland and other Nordic countries],” added Dr. Blondin, of the faculty of medicine and health sciences, University of Sherbrooke (Que.)

“While it can certainly be uncomfortable at first (like starting an exercise program), we adapt very quickly,” he added.
 

1 hour in a cold-water suit to induce shivering

In the current study, Dr. Sellers exposed adults (aged 40-75 years; 11 men and 4 postmenopausal women) with overweight/obesity (body mass index, 27-35 kg/m²) to 10 consecutive cold exposures of at least 1 hour of shivering per cold exposure.

“The shivering in this new research was more intense [than in prior studies] and was induced with a different cold exposure method – a 10° C water-perfused suit [compared with a prior study of 14-15° C, 6 hours/day]. This facilitated a shorter cold exposure duration, deemed feasible for the participants,” explained Dr. Sellers.

“At baseline, participants had glucose and A1c levels at the upper end of the normal criteria [5.5 mmol/l and 5.4%, respectively],” he said, referring to measurements that were suggestive of possible progression to type 2 diabetes.

He explained how the cold exposure was applied. “We induced the cold with a water-perfused suit worn by the participant, through which water flows at 10° C, and this cools the participant. Eventually, the participant starts to shiver, and does so for at least 1 hour every morning for 10 days.”

Participants’ shivering-induced heat production was measured via surface electromyography and visual observation to confirm the presence of shivering. Both before and after the 10-day course of shivering, physiological measurements were taken in the morning while participants were at rest in an overnight fasted state, and under thermoneutral conditions. Blood pressure and fasting blood glucose were measured.

A 2-hour oral glucose tolerance test (OGTT) was conducted twice for each participant: on the morning before the 10-day course of shivering and again on the morning after the final 10th day of shivering.

The primary endpoint was change from before to after the 10-day shivering intervention, as represented by the total area under the curve of glucose levels over time during the OGTT. 

“This provides a measure of the glucose concentrations in the blood before and after the 10 shivering sessions over the 10 days.”

courtesy Sten van Beek

Fasting glucose and blood lipids fall, glucose tolerance improves

After 10 shivering sessions, mean fasting plasma glucose decreased significantly in 13 out of the 15 participants, compared with before the first session (from 5.84 mmol/L to 5.67 mmol/L; P = .013).

Glucose tolerance during the OGTT improved by 6% (P = .041). “We can see that this was not due to a change in their insulin concentrations in the blood,” remarked Dr. Sellers, referring to the finding that plasma insulin concentrations at baseline and during the OGTT did not change.

Fasting plasma triglyceride and free-fatty acid concentrations also decreased significantly by 32% (P = .001) and 11% (P = .036), respectively.

“This is important because free-fatty acids are involved in the role of insulin resistance,” said Dr. Sellers. “In addition, the large reduction in serum triglycerides could have implications for atherosclerosis, which may also be beneficial.”

Dr. Sellers also found that systolic blood pressure decreased by 10 mm Hg or 7.4% (P < .001), while diastolic blood pressure decreased by 7 mm Hg or 8.1% (P < .001) on average. This lowering was seen in all participants.

“Again, quite strikingly, all participants showed” a reduction in blood pressure, said Dr. Sellers, which he noted relates to a decrease in resting heart rate (P = .062).
 

Brown fat or skeletal muscle contraction?

Dr. Sellers pointed out that, despite nonshivering thermogenesis being involved in mild cold acclimation, the data so far suggest that some level of mild muscle activity or shivering appears crucial in provoking the beneficial metabolic effects of cold acclimation.

“Brown fat is a metabolic heating system inside our bodies, burning calories”, explained Dr. Sellers. “This generates heat and prevents calories from being deposited as normal white fat. Brown fat is activated during cold and when we eat, but its activity is less in older adults and in individuals with obesity and diabetes.”

“Going forward, we might investigate the effects of shorter duration – so more intense shivering – to try and elucidate more precisely the optimum duration and intensity of shivering needed,” said Dr. Sellers.

“Our findings are promising and may have important health implications. In future studies, we plan to assess the effect of shivering in adults with type 2 diabetes,” he concluded.

Dr. Seller and Dr. Krook have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.

Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.

Lisovskaya/iStock/Getty Images Plus

Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
 

Diet also has role in improving survival in those with type 2 diabetes

Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.

By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.

“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”

She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.

“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”

Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.

The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
 

High versus low intake of various dietary factors

The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.  

Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.

Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).

A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).

Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).

Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.

“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.

She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.  

Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.

Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.

Lisovskaya/iStock/Getty Images Plus

Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
 

Diet also has role in improving survival in those with type 2 diabetes

Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.

By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.

“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”

She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.

“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”

Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.

The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
 

High versus low intake of various dietary factors

The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.  

Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.

Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).

A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).

Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).

Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.

“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.

She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.  

Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.

Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.

Lisovskaya/iStock/Getty Images Plus

Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
 

Diet also has role in improving survival in those with type 2 diabetes

Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.

By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.

“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”

She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.

“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”

Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.

The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
 

High versus low intake of various dietary factors

The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.  

Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.

Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).

A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).

Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).

Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.

“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.

She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.  

Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.