Becky McCall

COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly sixfold, according to data from the first study to investigate the association between ED and COVID-19 in young men in a real-life setting.

The preliminary data also indicated that ED is a marker of increased susceptibility to SARS-CoV-2 infection. Men with ED are more than five times more likely to have COVID-19 (odds ratio, 5.27).

For men with a history of COVID-19, the odds ratio of developing ED was 5.66. The strength of the association remained after adjusting for factors considered to affect ED.

The study, which was led by Emmanuele A. Jannini, MD, professor of endocrinology and medical sexology, University of Rome Tor Vergata, was published on March 20 in Andrology.
 

‘Mask up to keep it up’

ED can be both a short-term and a long-term complication of COVID-19, Dr. Jannini suggests.

“When offered, men should have the COVID vaccination. It also gives a whole new meaning to wearing the mask – mask up to keep it up,” he said. “It could possibly have the added benefit of preventing sexual dysfunction.”

He points out that older age, diabetes, high body mass index, and smoking increase the risk of contracting COVID-19.

“These are the same as risk factors for ED. Results of our study agree with the pathophysiological mechanisms linking ED, endothelial dysfunction, and COVID-19. Basically, endothelial dysfunction is common in both conditions [COVID-10 and ED].

“We would like to find some sort of biomarker of endothelial dysfunction post COVID, because it seems that there are many sequelae that coexist for a long time after infection,” added Dr. Jannini. “Asking a patient if they have ED after COVID might provide a measure of systemic wellness.”

Allan Pacey, MD, professor of andrology at the University of Sheffield (England), welcomed the research, noting, “This seems to be a well-conducted study. However, at the moment, the relationship is just a correlation, and it might be that some of the comorbidities that increased the men’s chances of getting a significant COVID-19 infection may have also independently increased their chances of erectile dysfunction.

“But the authors offer a plausible mechanism by which COVID-19 may impact directly on erectile function,” agrees Dr. Pacey. However, “There’s more work to be done,” he said. “I’d also argue it’s a good reason for men to wear a mask, practice social distancing, and take the vaccine when it’s offered to them.”

Urologist John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York, remarked, “It was a highly preliminary study, but the data are suggestive of a potential link between COVID-19 infection and ED.

“However, it raises enough questions such that further large, more long-term analyses are required to define causation. Future studies assessing testosterone levels and erectile hemodynamics will be needed to provide definite evidence of a causative link,» he stressed.
 

Erectile problems a ‘hallmark’ of systemic endothelial dysfunction

Prior research has suggested that asymptomatic COVID-19 could be associated with subclinical microvascular involvement with long-term cardiovascular effects.

“Indeed, COVID-19 is by all means an endothelial disease, in which systemic manifestations ... can potentially be due to alterations in the endothelial thrombotic/fibrinolytic balance,” emphasized Dr. Jannini. “In addition, endothelial cells express many of the cofactors used by SARS-CoV-2 to invade host cells.

“Erectile dysfunction has often been considered a hallmark of endothelial dysfunction, and as such, a potential association between ED and COVID-19 has also been postulated and underpinned the investigation in this study,” he explained.

The study was predicated on the fact that ED is often considered a clinical marker of impaired overall health status, which often features cardiovascular events at an early age. It aimed to investigate the bidirectional relationship between COVID-19 and ED. It asked whether ED could be a risk factor for contracting COVID-19 and whether having COVID-19 predisposes to developing ED.

“This would possibly suggest that men with ED, due to the underlying conditions which impair erectile response, could also be more susceptible to contracting COVID-19,” said Dr. Jannini.

Data were drawn from the Sex@COVID online survey, which was conducted from April 7 to May 4, 2020, in Italy. The survey included 6,821 participants aged 18 years or older (4,177 women; 2,644 men; mean age, 32.83 ± 11.24 years). Participants were stratified on the basis of marital status and sexual activity during lockdown. From these participants, 985 sexually active men were identified, among whom 25 (2.54%) reported having tested positive for COVID-19. These persons were matched with 75 COVID-19–negative men using propensity score matching in a 1:3 ratio.

The researchers used standardized psychometric tools to measure the effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of the participants.

Erectile function was measured with the International Index of Erectile Function or the Sexual Health Inventory for Men, which are often used in clinical settings. In light of the two-way interaction between sexual activity and psychological well-being, results were adjusted for any influence of anxiety and depression, which were measured with recognized scales for use in patients with a history of COVID-19.

Results showed that the prevalence of ED was significantly higher among men who self-reported a history of COVID-19, compared with a matching COVID-negative population (28% vs. 9.33%; P = .027).

After adjusting for variables that are considered to have a bearing on the development of ED, such as psychological status, age, and BMI, the odds ratio for developing ED after having had COVID-19 was 5.66 (95% confidence interval, 1.50-24.01).

Similarly, after adjusting for age and BMI, men with ED were more likely to have COVID‐19 (OR, 5.27; 95% CI, 1.49-20.09).

The authors note that persons who experience “a sudden onset or worsening of ED might also consider precautionary quarantine or nasopharyngeal swab, as COVID‐19 might act as a potential initiating trigger for the onset of erectile impairment, or an aggravating factor for its progression to more severe forms.”

Similarly, patients who have ED “should consider their erectile impairment as a sign of possible underlying conditions that could increase the likelihood of suffering from COVID‐19,” they write.

Dr. Mulhall highlighted several limitations of the study, including its retrospective nature, recall bias associated with the use of online questionnaires, and the inclusion of COVID‐19 diagnoses that were based on the response to the survey rather than on testing with nasopharyngeal swabs. In addition, comorbidity data were incomplete, and there was no indication of duration after COVID-19 infection, the severity of COVID-19, or the severity of ED.

The authors have disclosed no relevant financial relationships. Dr. Pacey is chairman of the advisory committee of the U.K. National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, trustee of the Progress Educational Trust, and trustee of the British Fertility Society (all unpaid). Dr. Mulhall has disclosed no relevant financial relationships.

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

COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly sixfold, according to data from the first study to investigate the association between ED and COVID-19 in young men in a real-life setting.

The preliminary data also indicated that ED is a marker of increased susceptibility to SARS-CoV-2 infection. Men with ED are more than five times more likely to have COVID-19 (odds ratio, 5.27).

For men with a history of COVID-19, the odds ratio of developing ED was 5.66. The strength of the association remained after adjusting for factors considered to affect ED.

The study, which was led by Emmanuele A. Jannini, MD, professor of endocrinology and medical sexology, University of Rome Tor Vergata, was published on March 20 in Andrology.
 

‘Mask up to keep it up’

ED can be both a short-term and a long-term complication of COVID-19, Dr. Jannini suggests.

“When offered, men should have the COVID vaccination. It also gives a whole new meaning to wearing the mask – mask up to keep it up,” he said. “It could possibly have the added benefit of preventing sexual dysfunction.”

He points out that older age, diabetes, high body mass index, and smoking increase the risk of contracting COVID-19.

“These are the same as risk factors for ED. Results of our study agree with the pathophysiological mechanisms linking ED, endothelial dysfunction, and COVID-19. Basically, endothelial dysfunction is common in both conditions [COVID-10 and ED].

“We would like to find some sort of biomarker of endothelial dysfunction post COVID, because it seems that there are many sequelae that coexist for a long time after infection,” added Dr. Jannini. “Asking a patient if they have ED after COVID might provide a measure of systemic wellness.”

Allan Pacey, MD, professor of andrology at the University of Sheffield (England), welcomed the research, noting, “This seems to be a well-conducted study. However, at the moment, the relationship is just a correlation, and it might be that some of the comorbidities that increased the men’s chances of getting a significant COVID-19 infection may have also independently increased their chances of erectile dysfunction.

“But the authors offer a plausible mechanism by which COVID-19 may impact directly on erectile function,” agrees Dr. Pacey. However, “There’s more work to be done,” he said. “I’d also argue it’s a good reason for men to wear a mask, practice social distancing, and take the vaccine when it’s offered to them.”

Urologist John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York, remarked, “It was a highly preliminary study, but the data are suggestive of a potential link between COVID-19 infection and ED.

“However, it raises enough questions such that further large, more long-term analyses are required to define causation. Future studies assessing testosterone levels and erectile hemodynamics will be needed to provide definite evidence of a causative link,» he stressed.
 

Erectile problems a ‘hallmark’ of systemic endothelial dysfunction

Prior research has suggested that asymptomatic COVID-19 could be associated with subclinical microvascular involvement with long-term cardiovascular effects.

“Indeed, COVID-19 is by all means an endothelial disease, in which systemic manifestations ... can potentially be due to alterations in the endothelial thrombotic/fibrinolytic balance,” emphasized Dr. Jannini. “In addition, endothelial cells express many of the cofactors used by SARS-CoV-2 to invade host cells.

“Erectile dysfunction has often been considered a hallmark of endothelial dysfunction, and as such, a potential association between ED and COVID-19 has also been postulated and underpinned the investigation in this study,” he explained.

The study was predicated on the fact that ED is often considered a clinical marker of impaired overall health status, which often features cardiovascular events at an early age. It aimed to investigate the bidirectional relationship between COVID-19 and ED. It asked whether ED could be a risk factor for contracting COVID-19 and whether having COVID-19 predisposes to developing ED.

“This would possibly suggest that men with ED, due to the underlying conditions which impair erectile response, could also be more susceptible to contracting COVID-19,” said Dr. Jannini.

Data were drawn from the Sex@COVID online survey, which was conducted from April 7 to May 4, 2020, in Italy. The survey included 6,821 participants aged 18 years or older (4,177 women; 2,644 men; mean age, 32.83 ± 11.24 years). Participants were stratified on the basis of marital status and sexual activity during lockdown. From these participants, 985 sexually active men were identified, among whom 25 (2.54%) reported having tested positive for COVID-19. These persons were matched with 75 COVID-19–negative men using propensity score matching in a 1:3 ratio.

The researchers used standardized psychometric tools to measure the effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of the participants.

Erectile function was measured with the International Index of Erectile Function or the Sexual Health Inventory for Men, which are often used in clinical settings. In light of the two-way interaction between sexual activity and psychological well-being, results were adjusted for any influence of anxiety and depression, which were measured with recognized scales for use in patients with a history of COVID-19.

Results showed that the prevalence of ED was significantly higher among men who self-reported a history of COVID-19, compared with a matching COVID-negative population (28% vs. 9.33%; P = .027).

After adjusting for variables that are considered to have a bearing on the development of ED, such as psychological status, age, and BMI, the odds ratio for developing ED after having had COVID-19 was 5.66 (95% confidence interval, 1.50-24.01).

Similarly, after adjusting for age and BMI, men with ED were more likely to have COVID‐19 (OR, 5.27; 95% CI, 1.49-20.09).

The authors note that persons who experience “a sudden onset or worsening of ED might also consider precautionary quarantine or nasopharyngeal swab, as COVID‐19 might act as a potential initiating trigger for the onset of erectile impairment, or an aggravating factor for its progression to more severe forms.”

Similarly, patients who have ED “should consider their erectile impairment as a sign of possible underlying conditions that could increase the likelihood of suffering from COVID‐19,” they write.

Dr. Mulhall highlighted several limitations of the study, including its retrospective nature, recall bias associated with the use of online questionnaires, and the inclusion of COVID‐19 diagnoses that were based on the response to the survey rather than on testing with nasopharyngeal swabs. In addition, comorbidity data were incomplete, and there was no indication of duration after COVID-19 infection, the severity of COVID-19, or the severity of ED.

The authors have disclosed no relevant financial relationships. Dr. Pacey is chairman of the advisory committee of the U.K. National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, trustee of the Progress Educational Trust, and trustee of the British Fertility Society (all unpaid). Dr. Mulhall has disclosed no relevant financial relationships.

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

COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly sixfold, according to data from the first study to investigate the association between ED and COVID-19 in young men in a real-life setting.

The preliminary data also indicated that ED is a marker of increased susceptibility to SARS-CoV-2 infection. Men with ED are more than five times more likely to have COVID-19 (odds ratio, 5.27).

For men with a history of COVID-19, the odds ratio of developing ED was 5.66. The strength of the association remained after adjusting for factors considered to affect ED.

The study, which was led by Emmanuele A. Jannini, MD, professor of endocrinology and medical sexology, University of Rome Tor Vergata, was published on March 20 in Andrology.
 

‘Mask up to keep it up’

ED can be both a short-term and a long-term complication of COVID-19, Dr. Jannini suggests.

“When offered, men should have the COVID vaccination. It also gives a whole new meaning to wearing the mask – mask up to keep it up,” he said. “It could possibly have the added benefit of preventing sexual dysfunction.”

He points out that older age, diabetes, high body mass index, and smoking increase the risk of contracting COVID-19.

“These are the same as risk factors for ED. Results of our study agree with the pathophysiological mechanisms linking ED, endothelial dysfunction, and COVID-19. Basically, endothelial dysfunction is common in both conditions [COVID-10 and ED].

“We would like to find some sort of biomarker of endothelial dysfunction post COVID, because it seems that there are many sequelae that coexist for a long time after infection,” added Dr. Jannini. “Asking a patient if they have ED after COVID might provide a measure of systemic wellness.”

Allan Pacey, MD, professor of andrology at the University of Sheffield (England), welcomed the research, noting, “This seems to be a well-conducted study. However, at the moment, the relationship is just a correlation, and it might be that some of the comorbidities that increased the men’s chances of getting a significant COVID-19 infection may have also independently increased their chances of erectile dysfunction.

“But the authors offer a plausible mechanism by which COVID-19 may impact directly on erectile function,” agrees Dr. Pacey. However, “There’s more work to be done,” he said. “I’d also argue it’s a good reason for men to wear a mask, practice social distancing, and take the vaccine when it’s offered to them.”

Urologist John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York, remarked, “It was a highly preliminary study, but the data are suggestive of a potential link between COVID-19 infection and ED.

“However, it raises enough questions such that further large, more long-term analyses are required to define causation. Future studies assessing testosterone levels and erectile hemodynamics will be needed to provide definite evidence of a causative link,» he stressed.
 

Erectile problems a ‘hallmark’ of systemic endothelial dysfunction

Prior research has suggested that asymptomatic COVID-19 could be associated with subclinical microvascular involvement with long-term cardiovascular effects.

“Indeed, COVID-19 is by all means an endothelial disease, in which systemic manifestations ... can potentially be due to alterations in the endothelial thrombotic/fibrinolytic balance,” emphasized Dr. Jannini. “In addition, endothelial cells express many of the cofactors used by SARS-CoV-2 to invade host cells.

“Erectile dysfunction has often been considered a hallmark of endothelial dysfunction, and as such, a potential association between ED and COVID-19 has also been postulated and underpinned the investigation in this study,” he explained.

The study was predicated on the fact that ED is often considered a clinical marker of impaired overall health status, which often features cardiovascular events at an early age. It aimed to investigate the bidirectional relationship between COVID-19 and ED. It asked whether ED could be a risk factor for contracting COVID-19 and whether having COVID-19 predisposes to developing ED.

“This would possibly suggest that men with ED, due to the underlying conditions which impair erectile response, could also be more susceptible to contracting COVID-19,” said Dr. Jannini.

Data were drawn from the Sex@COVID online survey, which was conducted from April 7 to May 4, 2020, in Italy. The survey included 6,821 participants aged 18 years or older (4,177 women; 2,644 men; mean age, 32.83 ± 11.24 years). Participants were stratified on the basis of marital status and sexual activity during lockdown. From these participants, 985 sexually active men were identified, among whom 25 (2.54%) reported having tested positive for COVID-19. These persons were matched with 75 COVID-19–negative men using propensity score matching in a 1:3 ratio.

The researchers used standardized psychometric tools to measure the effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of the participants.

Erectile function was measured with the International Index of Erectile Function or the Sexual Health Inventory for Men, which are often used in clinical settings. In light of the two-way interaction between sexual activity and psychological well-being, results were adjusted for any influence of anxiety and depression, which were measured with recognized scales for use in patients with a history of COVID-19.

Results showed that the prevalence of ED was significantly higher among men who self-reported a history of COVID-19, compared with a matching COVID-negative population (28% vs. 9.33%; P = .027).

After adjusting for variables that are considered to have a bearing on the development of ED, such as psychological status, age, and BMI, the odds ratio for developing ED after having had COVID-19 was 5.66 (95% confidence interval, 1.50-24.01).

Similarly, after adjusting for age and BMI, men with ED were more likely to have COVID‐19 (OR, 5.27; 95% CI, 1.49-20.09).

The authors note that persons who experience “a sudden onset or worsening of ED might also consider precautionary quarantine or nasopharyngeal swab, as COVID‐19 might act as a potential initiating trigger for the onset of erectile impairment, or an aggravating factor for its progression to more severe forms.”

Similarly, patients who have ED “should consider their erectile impairment as a sign of possible underlying conditions that could increase the likelihood of suffering from COVID‐19,” they write.

Dr. Mulhall highlighted several limitations of the study, including its retrospective nature, recall bias associated with the use of online questionnaires, and the inclusion of COVID‐19 diagnoses that were based on the response to the survey rather than on testing with nasopharyngeal swabs. In addition, comorbidity data were incomplete, and there was no indication of duration after COVID-19 infection, the severity of COVID-19, or the severity of ED.

The authors have disclosed no relevant financial relationships. Dr. Pacey is chairman of the advisory committee of the U.K. National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, trustee of the Progress Educational Trust, and trustee of the British Fertility Society (all unpaid). Dr. Mulhall has disclosed no relevant financial relationships.

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Higher levels of vitamin D than traditionally considered sufficient may help prevent COVID-19 infection – particularly in Black patients, shows a new single-center, retrospective study looking at the role of vitamin D in prevention of infection.

The study, published recently in JAMA Network Open, noted that expert opinion varies as to what “sufficient” levels of vitamin D are, some define this as 30 ng/mL, while others cite 40 ng/mL or greater.

In their discussion, the authors also noted that their results showed the “risk of positive COVID-19 test results decreased significantly with increased vitamin D level of 30 ng/mL or greater when measured as a continuous variable.”

“These new results tell us that having vitamin D levels above those normally considered sufficient is associated with decreased risk of testing positive for COVID-19, at least in Black individuals,” lead author, David Meltzer, MD, chief of hospital medicine at the University of Chicago, said in a press release from his institution.

“These findings suggest that randomized clinical trials to determine whether increasing vitamin D levels to greater than 30-40 ng/mL affect COVID-19 risk are warranted, especially in Black individuals,” he and his coauthors said.
 

Vitamin D at time of testing most strongly associated with COVID risk

An earlier study by the same researchers found that vitamin D deficiency (less than 20 ng/mL) may raise the risk of testing positive for COVID-19 in people from various ethnicities, as reported by this news organization.

Data for this latest study were drawn from electronic health records for 4,638 individuals at the University of Chicago Medicine and were used to examine whether the likelihood of a positive COVID-19 test was associated with a person’s most recent vitamin D level (within the previous year), and whether there was any effect of ethnicity on this outcome.

Mean age was 52.8 years, 69% were women, 49% were Black, 43% White, and 8% were another race/ethnicity. A total of 27% of the individuals were deficient in vitamin D (less than 20 ng/mL), 27% had insufficient levels (20-30 ng/mL), 22% had sufficient levels (30-40 ng/mL), and the remaining 24% had levels of 40 ng/mL or greater.

In total, 333 (7%) of people tested positive for COVID-19, including 102 (5%) Whites and 211 (9%) Blacks. And 36% of Black individuals who tested positive for COVID-19 were classified as vitamin D deficient, compared with 16% of Whites.

A positive test result for COVID-19 was not significantly associated with vitamin D levels in white individuals but was in Black individuals.

In Black people, compared with levels of at least 40 ng/mL, vitamin D levels of 30-40 ng/mL were associated with an incidence rate ratio of 2.64 for COVID-19 positivity (P = .01). For levels of 20-30 ng/mL, the IRR was 1.69 (P = 0.21); and for less than 20 ng/mL the IRR was 2.55 (P = .009).

The researchers also found that the risk of positive test results with lower vitamin D levels increased when those levels were lower just prior to the positive COVID-19 test, lending “support [to] the idea that vitamin D level at the time of testing is most strongly associated with COVID-19 risk,” they wrote.
 

Try upping vitamin D levels to 40 ng/mL or greater to prevent COVID?

In their discussion, the authors noted that significant association of vitamin D levels with COVID-19 risk in Blacks but not in Whites, “could reflect their higher COVID-19 risk, to which socioeconomic factors and structural inequities clearly contribute.

“Biological susceptibility to vitamin D deficiency may also be less frequent in White than Black individuals, since lighter skin increases vitamin D production in response to sunlight, and vitamin D binding proteins may vary by race and affect vitamin D bioavailability.”

Given less than 10% of U.S. adults have a vitamin D level greater than 40 ng/mL, the study findings increase the urgency to consider whether increased sun exposure or supplementation could reduce COVID-19 risk, according to the authors.

“When increased sun exposure is impractical, achieving vitamin D levels of 40 ng/mL or greater typically requires greater supplementation than currently recommended for most individuals of 600-800 IU/d vitamin D3,” they added.

However, Dr. Meltzer also acknowledged that “this is an observational study. We can see that there’s an association between vitamin D levels and likelihood of a COVID-19 diagnosis, but we don’t know exactly why that is, or whether these results are due to the vitamin D directly or other related biological factors.”

All in all, the authors suggested that randomized clinical trials are needed to understand if vitamin D can reduce COVID-19 risk, and as such they should include doses of supplements likely to increase vitamin D to at least 40 ng/mL, and perhaps even higher, although they pointed out that the latter must be achieved safely.

“Studies should also consider the role of vitamin D testing, loading doses, dose adjustments for individuals who are obese or overweight, risks for hypercalcemia, and strategies to monitor for and mitigate hypercalcemia, and that non-White populations, such as Black individuals, may have greater needs for supplementation,” they outlined.

They are now recruiting participants for two separate clinical trials testing the efficacy of vitamin D supplements for preventing COVID-19.

The authors disclosed no relevant financial relationships.

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

Higher levels of vitamin D than traditionally considered sufficient may help prevent COVID-19 infection – particularly in Black patients, shows a new single-center, retrospective study looking at the role of vitamin D in prevention of infection.

The study, published recently in JAMA Network Open, noted that expert opinion varies as to what “sufficient” levels of vitamin D are, some define this as 30 ng/mL, while others cite 40 ng/mL or greater.

In their discussion, the authors also noted that their results showed the “risk of positive COVID-19 test results decreased significantly with increased vitamin D level of 30 ng/mL or greater when measured as a continuous variable.”

“These new results tell us that having vitamin D levels above those normally considered sufficient is associated with decreased risk of testing positive for COVID-19, at least in Black individuals,” lead author, David Meltzer, MD, chief of hospital medicine at the University of Chicago, said in a press release from his institution.

“These findings suggest that randomized clinical trials to determine whether increasing vitamin D levels to greater than 30-40 ng/mL affect COVID-19 risk are warranted, especially in Black individuals,” he and his coauthors said.
 

Vitamin D at time of testing most strongly associated with COVID risk

An earlier study by the same researchers found that vitamin D deficiency (less than 20 ng/mL) may raise the risk of testing positive for COVID-19 in people from various ethnicities, as reported by this news organization.

Data for this latest study were drawn from electronic health records for 4,638 individuals at the University of Chicago Medicine and were used to examine whether the likelihood of a positive COVID-19 test was associated with a person’s most recent vitamin D level (within the previous year), and whether there was any effect of ethnicity on this outcome.

Mean age was 52.8 years, 69% were women, 49% were Black, 43% White, and 8% were another race/ethnicity. A total of 27% of the individuals were deficient in vitamin D (less than 20 ng/mL), 27% had insufficient levels (20-30 ng/mL), 22% had sufficient levels (30-40 ng/mL), and the remaining 24% had levels of 40 ng/mL or greater.

In total, 333 (7%) of people tested positive for COVID-19, including 102 (5%) Whites and 211 (9%) Blacks. And 36% of Black individuals who tested positive for COVID-19 were classified as vitamin D deficient, compared with 16% of Whites.

A positive test result for COVID-19 was not significantly associated with vitamin D levels in white individuals but was in Black individuals.

In Black people, compared with levels of at least 40 ng/mL, vitamin D levels of 30-40 ng/mL were associated with an incidence rate ratio of 2.64 for COVID-19 positivity (P = .01). For levels of 20-30 ng/mL, the IRR was 1.69 (P = 0.21); and for less than 20 ng/mL the IRR was 2.55 (P = .009).

The researchers also found that the risk of positive test results with lower vitamin D levels increased when those levels were lower just prior to the positive COVID-19 test, lending “support [to] the idea that vitamin D level at the time of testing is most strongly associated with COVID-19 risk,” they wrote.
 

Try upping vitamin D levels to 40 ng/mL or greater to prevent COVID?

In their discussion, the authors noted that significant association of vitamin D levels with COVID-19 risk in Blacks but not in Whites, “could reflect their higher COVID-19 risk, to which socioeconomic factors and structural inequities clearly contribute.

“Biological susceptibility to vitamin D deficiency may also be less frequent in White than Black individuals, since lighter skin increases vitamin D production in response to sunlight, and vitamin D binding proteins may vary by race and affect vitamin D bioavailability.”

Given less than 10% of U.S. adults have a vitamin D level greater than 40 ng/mL, the study findings increase the urgency to consider whether increased sun exposure or supplementation could reduce COVID-19 risk, according to the authors.

“When increased sun exposure is impractical, achieving vitamin D levels of 40 ng/mL or greater typically requires greater supplementation than currently recommended for most individuals of 600-800 IU/d vitamin D3,” they added.

However, Dr. Meltzer also acknowledged that “this is an observational study. We can see that there’s an association between vitamin D levels and likelihood of a COVID-19 diagnosis, but we don’t know exactly why that is, or whether these results are due to the vitamin D directly or other related biological factors.”

All in all, the authors suggested that randomized clinical trials are needed to understand if vitamin D can reduce COVID-19 risk, and as such they should include doses of supplements likely to increase vitamin D to at least 40 ng/mL, and perhaps even higher, although they pointed out that the latter must be achieved safely.

“Studies should also consider the role of vitamin D testing, loading doses, dose adjustments for individuals who are obese or overweight, risks for hypercalcemia, and strategies to monitor for and mitigate hypercalcemia, and that non-White populations, such as Black individuals, may have greater needs for supplementation,” they outlined.

They are now recruiting participants for two separate clinical trials testing the efficacy of vitamin D supplements for preventing COVID-19.

The authors disclosed no relevant financial relationships.

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

Higher levels of vitamin D than traditionally considered sufficient may help prevent COVID-19 infection – particularly in Black patients, shows a new single-center, retrospective study looking at the role of vitamin D in prevention of infection.

The study, published recently in JAMA Network Open, noted that expert opinion varies as to what “sufficient” levels of vitamin D are, some define this as 30 ng/mL, while others cite 40 ng/mL or greater.

In their discussion, the authors also noted that their results showed the “risk of positive COVID-19 test results decreased significantly with increased vitamin D level of 30 ng/mL or greater when measured as a continuous variable.”

“These new results tell us that having vitamin D levels above those normally considered sufficient is associated with decreased risk of testing positive for COVID-19, at least in Black individuals,” lead author, David Meltzer, MD, chief of hospital medicine at the University of Chicago, said in a press release from his institution.

“These findings suggest that randomized clinical trials to determine whether increasing vitamin D levels to greater than 30-40 ng/mL affect COVID-19 risk are warranted, especially in Black individuals,” he and his coauthors said.
 

Vitamin D at time of testing most strongly associated with COVID risk

An earlier study by the same researchers found that vitamin D deficiency (less than 20 ng/mL) may raise the risk of testing positive for COVID-19 in people from various ethnicities, as reported by this news organization.

Data for this latest study were drawn from electronic health records for 4,638 individuals at the University of Chicago Medicine and were used to examine whether the likelihood of a positive COVID-19 test was associated with a person’s most recent vitamin D level (within the previous year), and whether there was any effect of ethnicity on this outcome.

Mean age was 52.8 years, 69% were women, 49% were Black, 43% White, and 8% were another race/ethnicity. A total of 27% of the individuals were deficient in vitamin D (less than 20 ng/mL), 27% had insufficient levels (20-30 ng/mL), 22% had sufficient levels (30-40 ng/mL), and the remaining 24% had levels of 40 ng/mL or greater.

In total, 333 (7%) of people tested positive for COVID-19, including 102 (5%) Whites and 211 (9%) Blacks. And 36% of Black individuals who tested positive for COVID-19 were classified as vitamin D deficient, compared with 16% of Whites.

A positive test result for COVID-19 was not significantly associated with vitamin D levels in white individuals but was in Black individuals.

In Black people, compared with levels of at least 40 ng/mL, vitamin D levels of 30-40 ng/mL were associated with an incidence rate ratio of 2.64 for COVID-19 positivity (P = .01). For levels of 20-30 ng/mL, the IRR was 1.69 (P = 0.21); and for less than 20 ng/mL the IRR was 2.55 (P = .009).

The researchers also found that the risk of positive test results with lower vitamin D levels increased when those levels were lower just prior to the positive COVID-19 test, lending “support [to] the idea that vitamin D level at the time of testing is most strongly associated with COVID-19 risk,” they wrote.
 

Try upping vitamin D levels to 40 ng/mL or greater to prevent COVID?

In their discussion, the authors noted that significant association of vitamin D levels with COVID-19 risk in Blacks but not in Whites, “could reflect their higher COVID-19 risk, to which socioeconomic factors and structural inequities clearly contribute.

“Biological susceptibility to vitamin D deficiency may also be less frequent in White than Black individuals, since lighter skin increases vitamin D production in response to sunlight, and vitamin D binding proteins may vary by race and affect vitamin D bioavailability.”

Given less than 10% of U.S. adults have a vitamin D level greater than 40 ng/mL, the study findings increase the urgency to consider whether increased sun exposure or supplementation could reduce COVID-19 risk, according to the authors.

“When increased sun exposure is impractical, achieving vitamin D levels of 40 ng/mL or greater typically requires greater supplementation than currently recommended for most individuals of 600-800 IU/d vitamin D3,” they added.

However, Dr. Meltzer also acknowledged that “this is an observational study. We can see that there’s an association between vitamin D levels and likelihood of a COVID-19 diagnosis, but we don’t know exactly why that is, or whether these results are due to the vitamin D directly or other related biological factors.”

All in all, the authors suggested that randomized clinical trials are needed to understand if vitamin D can reduce COVID-19 risk, and as such they should include doses of supplements likely to increase vitamin D to at least 40 ng/mL, and perhaps even higher, although they pointed out that the latter must be achieved safely.

“Studies should also consider the role of vitamin D testing, loading doses, dose adjustments for individuals who are obese or overweight, risks for hypercalcemia, and strategies to monitor for and mitigate hypercalcemia, and that non-White populations, such as Black individuals, may have greater needs for supplementation,” they outlined.

They are now recruiting participants for two separate clinical trials testing the efficacy of vitamin D supplements for preventing COVID-19.

The authors disclosed no relevant financial relationships.

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

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

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

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

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

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

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

Vitamin D deficiency on admission to hospital was associated with a 3.7-fold increase in the odds of dying from COVID-19, according to an observational study looking back at data from the first wave of the pandemic.

Nearly 60% of patients with COVID-19 were vitamin D deficient upon hospitalization, with men in the advanced stages of COVID-19 pneumonia showing the greatest deficit.

Importantly, the results were independent of comorbidities known to be affected by vitamin D deficiency, wrote the authors, led by Dieter De Smet, MD, from AZ Delta General Hospital, Roeselare, Belgium.

“[The findings] highlight the need for randomized, controlled trials specifically targeting vitamin D–deficient patients at intake, and make a call for general avoidance of vitamin D deficiency as a safe and inexpensive possible mitigation of the SARS-CoV-2 pandemic,” Dr. De Smet and colleagues wrote in their article, published online Nov. 25 in the American Journal of Clinical Pathology.

A search of ClinicalTrials.gov reveals there are currently close to 40 ongoing intervention trials with vitamin D in COVID-19 around the world for varying purposes, including prevention, and varying forms of treatment.
 

Consider vitamin D to prevent COVID-19 infection

With regard to the potential role in prevention, “Numerous observational studies have shown that low vitamin D levels are a major predictor for poor COVID outcomes,” noted Jacob Teitelbaum, MD, an internist who specializes in treating chronic fatigue syndrome and fibromyalgia who also has an interest in COVID-19.

“This study shows how severe a problem this is,” Dr. Teitelbaum said in an interview. “A 3.7-fold increase in death rate if someone’s vitamin D level was below 20 [ng/mL] is staggering. It is arguably one of the most important risk factors to consider.”

“What is not clear is whether vitamin D levels are acting as an acute-phase reactant, dropping because of the infection, with larger drops indicating more severe disease, or whether vitamin D deficiency is causing worse outcomes,” added Dr. Teitelbaum, who is director of the Center for Effective CFIDS/Fibromyalgia Therapies, Kailua-Kona, Hawaii.

Also asked to comment, Andrea Giustina, MD, president of the European Society of Endocrinology, said: “The paper by De Smet et al confirms what we already hypothesized in BMJ last March: that patients with low vitamin D levels are at high risk of hospitalization for COVID-19 and developing severe and lethal disease. This is likely due to the loss in the protective action of vitamin D on the immune system and against the SARS-CoV-2–induced cytokine storm.”

He said it is particularly interesting that the authors of the new study had reported more prevalent vitamin D deficiency among men than women, most likely because women are more often treated with vitamin D for osteoporosis.

The new study should prompt all clinicians and health authorities to seriously consider vitamin D supplementation as an additional tool in the fight against COVID-19, particularly for the prevention of infection in those at high risk of both COVID-19 and hypovitaminosis D, such the elderly, urged Dr. Giustina, of San Raffaele Vita-Salute University, Milan.
 

Results adjusted for multiple confounders

Dr. De Smet and colleagues looked at serum 25-hydroxyvitamin D (25[OH]D) levels in 186 patients hospitalized for severe COVID-19 infection as a function of radiologic stage of COVID-19 pneumonia as well as the association between vitamin D status on admission and COVID-19 mortality.

Cognizant of the potential for confounding by multiple factors, they adjusted for age, sex, and known vitamin D–affected comorbidities such as diabetes, chronic lung disease, and coronary artery disease.

Patients were hospitalized from March 1 to April 7, 2020 (the peak of the first wave of the pandemic) at their institution, AZ Delta General Hospital, a tertiary network hospital.

The mean age of patients was 69 years, 41% were women, and 59% had coronary artery disease. Upon admission to hospital, median vitamin D level was 18 ng/mL (women, 20.7 ng/mL; men, 17.6 ng/mL).

A remarkably high percentage (59%, 109/186) of patients with COVID-19 were vitamin D deficient (25[OH]D <20 ng/mL) when admitted (47% of women and 67% of men), wrote the authors.

“What surprises me,” said Dr. Teitelbaum, is that almost 60% “of these patients had 25(OH)D under 20 ng/mL but most clinicians consider under 50 to be low.”

All patients had a chest CT scan to determine the radiologic stage of COVID-19 pneumonia and serum vitamin D measurement on admission. Radiologic stage of pneumonia was used as a proxy for immunologic phase of COVID-19.
 

Vitamin D deficiency correlated with worsening pneumonia

Among men, rates of vitamin D deficiency increased with advancing disease, with rates of 55% in stage 1, 67% in stage 2, and up to 74% in stage 3 pneumonia.

There is therefore “a clear correlation between 25(OH)D level and temporal stages of viral pneumonia, particularly in male patients,” the authors wrote.

“Vitamin D dampens excessive inflammation,” said Dr. Teitelbaum. “In these patients with acute respiratory distress syndrome, the immune system has gone wild.”

“The study was carried out in Belgium, so there’s less sunlight there than some other places, but even here in Hawaii, with plenty of sunshine, we have vitamin D deficiency,” he added.

“More studies are needed, but I think there are enough data to suggest a multivitamin should be used to aid prophylaxis, and this is reflected in [some] infectious disease recommendations,” he noted.

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

Vitamin D deficiency on admission to hospital was associated with a 3.7-fold increase in the odds of dying from COVID-19, according to an observational study looking back at data from the first wave of the pandemic.

Nearly 60% of patients with COVID-19 were vitamin D deficient upon hospitalization, with men in the advanced stages of COVID-19 pneumonia showing the greatest deficit.

Importantly, the results were independent of comorbidities known to be affected by vitamin D deficiency, wrote the authors, led by Dieter De Smet, MD, from AZ Delta General Hospital, Roeselare, Belgium.

“[The findings] highlight the need for randomized, controlled trials specifically targeting vitamin D–deficient patients at intake, and make a call for general avoidance of vitamin D deficiency as a safe and inexpensive possible mitigation of the SARS-CoV-2 pandemic,” Dr. De Smet and colleagues wrote in their article, published online Nov. 25 in the American Journal of Clinical Pathology.

A search of ClinicalTrials.gov reveals there are currently close to 40 ongoing intervention trials with vitamin D in COVID-19 around the world for varying purposes, including prevention, and varying forms of treatment.
 

Consider vitamin D to prevent COVID-19 infection

With regard to the potential role in prevention, “Numerous observational studies have shown that low vitamin D levels are a major predictor for poor COVID outcomes,” noted Jacob Teitelbaum, MD, an internist who specializes in treating chronic fatigue syndrome and fibromyalgia who also has an interest in COVID-19.

“This study shows how severe a problem this is,” Dr. Teitelbaum said in an interview. “A 3.7-fold increase in death rate if someone’s vitamin D level was below 20 [ng/mL] is staggering. It is arguably one of the most important risk factors to consider.”

“What is not clear is whether vitamin D levels are acting as an acute-phase reactant, dropping because of the infection, with larger drops indicating more severe disease, or whether vitamin D deficiency is causing worse outcomes,” added Dr. Teitelbaum, who is director of the Center for Effective CFIDS/Fibromyalgia Therapies, Kailua-Kona, Hawaii.

Also asked to comment, Andrea Giustina, MD, president of the European Society of Endocrinology, said: “The paper by De Smet et al confirms what we already hypothesized in BMJ last March: that patients with low vitamin D levels are at high risk of hospitalization for COVID-19 and developing severe and lethal disease. This is likely due to the loss in the protective action of vitamin D on the immune system and against the SARS-CoV-2–induced cytokine storm.”

He said it is particularly interesting that the authors of the new study had reported more prevalent vitamin D deficiency among men than women, most likely because women are more often treated with vitamin D for osteoporosis.

The new study should prompt all clinicians and health authorities to seriously consider vitamin D supplementation as an additional tool in the fight against COVID-19, particularly for the prevention of infection in those at high risk of both COVID-19 and hypovitaminosis D, such the elderly, urged Dr. Giustina, of San Raffaele Vita-Salute University, Milan.
 

Results adjusted for multiple confounders

Dr. De Smet and colleagues looked at serum 25-hydroxyvitamin D (25[OH]D) levels in 186 patients hospitalized for severe COVID-19 infection as a function of radiologic stage of COVID-19 pneumonia as well as the association between vitamin D status on admission and COVID-19 mortality.

Cognizant of the potential for confounding by multiple factors, they adjusted for age, sex, and known vitamin D–affected comorbidities such as diabetes, chronic lung disease, and coronary artery disease.

Patients were hospitalized from March 1 to April 7, 2020 (the peak of the first wave of the pandemic) at their institution, AZ Delta General Hospital, a tertiary network hospital.

The mean age of patients was 69 years, 41% were women, and 59% had coronary artery disease. Upon admission to hospital, median vitamin D level was 18 ng/mL (women, 20.7 ng/mL; men, 17.6 ng/mL).

A remarkably high percentage (59%, 109/186) of patients with COVID-19 were vitamin D deficient (25[OH]D <20 ng/mL) when admitted (47% of women and 67% of men), wrote the authors.

“What surprises me,” said Dr. Teitelbaum, is that almost 60% “of these patients had 25(OH)D under 20 ng/mL but most clinicians consider under 50 to be low.”

All patients had a chest CT scan to determine the radiologic stage of COVID-19 pneumonia and serum vitamin D measurement on admission. Radiologic stage of pneumonia was used as a proxy for immunologic phase of COVID-19.
 

Vitamin D deficiency correlated with worsening pneumonia

Among men, rates of vitamin D deficiency increased with advancing disease, with rates of 55% in stage 1, 67% in stage 2, and up to 74% in stage 3 pneumonia.

There is therefore “a clear correlation between 25(OH)D level and temporal stages of viral pneumonia, particularly in male patients,” the authors wrote.

“Vitamin D dampens excessive inflammation,” said Dr. Teitelbaum. “In these patients with acute respiratory distress syndrome, the immune system has gone wild.”

“The study was carried out in Belgium, so there’s less sunlight there than some other places, but even here in Hawaii, with plenty of sunshine, we have vitamin D deficiency,” he added.

“More studies are needed, but I think there are enough data to suggest a multivitamin should be used to aid prophylaxis, and this is reflected in [some] infectious disease recommendations,” he noted.

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

Vitamin D deficiency on admission to hospital was associated with a 3.7-fold increase in the odds of dying from COVID-19, according to an observational study looking back at data from the first wave of the pandemic.

Nearly 60% of patients with COVID-19 were vitamin D deficient upon hospitalization, with men in the advanced stages of COVID-19 pneumonia showing the greatest deficit.

Importantly, the results were independent of comorbidities known to be affected by vitamin D deficiency, wrote the authors, led by Dieter De Smet, MD, from AZ Delta General Hospital, Roeselare, Belgium.

“[The findings] highlight the need for randomized, controlled trials specifically targeting vitamin D–deficient patients at intake, and make a call for general avoidance of vitamin D deficiency as a safe and inexpensive possible mitigation of the SARS-CoV-2 pandemic,” Dr. De Smet and colleagues wrote in their article, published online Nov. 25 in the American Journal of Clinical Pathology.

A search of ClinicalTrials.gov reveals there are currently close to 40 ongoing intervention trials with vitamin D in COVID-19 around the world for varying purposes, including prevention, and varying forms of treatment.
 

Consider vitamin D to prevent COVID-19 infection

With regard to the potential role in prevention, “Numerous observational studies have shown that low vitamin D levels are a major predictor for poor COVID outcomes,” noted Jacob Teitelbaum, MD, an internist who specializes in treating chronic fatigue syndrome and fibromyalgia who also has an interest in COVID-19.

“This study shows how severe a problem this is,” Dr. Teitelbaum said in an interview. “A 3.7-fold increase in death rate if someone’s vitamin D level was below 20 [ng/mL] is staggering. It is arguably one of the most important risk factors to consider.”

“What is not clear is whether vitamin D levels are acting as an acute-phase reactant, dropping because of the infection, with larger drops indicating more severe disease, or whether vitamin D deficiency is causing worse outcomes,” added Dr. Teitelbaum, who is director of the Center for Effective CFIDS/Fibromyalgia Therapies, Kailua-Kona, Hawaii.

Also asked to comment, Andrea Giustina, MD, president of the European Society of Endocrinology, said: “The paper by De Smet et al confirms what we already hypothesized in BMJ last March: that patients with low vitamin D levels are at high risk of hospitalization for COVID-19 and developing severe and lethal disease. This is likely due to the loss in the protective action of vitamin D on the immune system and against the SARS-CoV-2–induced cytokine storm.”

He said it is particularly interesting that the authors of the new study had reported more prevalent vitamin D deficiency among men than women, most likely because women are more often treated with vitamin D for osteoporosis.

The new study should prompt all clinicians and health authorities to seriously consider vitamin D supplementation as an additional tool in the fight against COVID-19, particularly for the prevention of infection in those at high risk of both COVID-19 and hypovitaminosis D, such the elderly, urged Dr. Giustina, of San Raffaele Vita-Salute University, Milan.
 

Results adjusted for multiple confounders

Dr. De Smet and colleagues looked at serum 25-hydroxyvitamin D (25[OH]D) levels in 186 patients hospitalized for severe COVID-19 infection as a function of radiologic stage of COVID-19 pneumonia as well as the association between vitamin D status on admission and COVID-19 mortality.

Cognizant of the potential for confounding by multiple factors, they adjusted for age, sex, and known vitamin D–affected comorbidities such as diabetes, chronic lung disease, and coronary artery disease.

Patients were hospitalized from March 1 to April 7, 2020 (the peak of the first wave of the pandemic) at their institution, AZ Delta General Hospital, a tertiary network hospital.

The mean age of patients was 69 years, 41% were women, and 59% had coronary artery disease. Upon admission to hospital, median vitamin D level was 18 ng/mL (women, 20.7 ng/mL; men, 17.6 ng/mL).

A remarkably high percentage (59%, 109/186) of patients with COVID-19 were vitamin D deficient (25[OH]D <20 ng/mL) when admitted (47% of women and 67% of men), wrote the authors.

“What surprises me,” said Dr. Teitelbaum, is that almost 60% “of these patients had 25(OH)D under 20 ng/mL but most clinicians consider under 50 to be low.”

All patients had a chest CT scan to determine the radiologic stage of COVID-19 pneumonia and serum vitamin D measurement on admission. Radiologic stage of pneumonia was used as a proxy for immunologic phase of COVID-19.
 

Vitamin D deficiency correlated with worsening pneumonia

Among men, rates of vitamin D deficiency increased with advancing disease, with rates of 55% in stage 1, 67% in stage 2, and up to 74% in stage 3 pneumonia.

There is therefore “a clear correlation between 25(OH)D level and temporal stages of viral pneumonia, particularly in male patients,” the authors wrote.

“Vitamin D dampens excessive inflammation,” said Dr. Teitelbaum. “In these patients with acute respiratory distress syndrome, the immune system has gone wild.”

“The study was carried out in Belgium, so there’s less sunlight there than some other places, but even here in Hawaii, with plenty of sunshine, we have vitamin D deficiency,” he added.

“More studies are needed, but I think there are enough data to suggest a multivitamin should be used to aid prophylaxis, and this is reflected in [some] infectious disease recommendations,” he noted.

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

Risk of intubation for COVID-19 in very sick hospitalized patients was increased over fivefold in those with diabetic retinopathy, compared with those without, in a small single-center study from the United Kingdom.

Importantly, the risk of intubation was independent of conventional risk factors for poor COVID-19 outcomes.

“People with preexisting diabetes-related vascular damage, such as retinopathy, might be predisposed to a more severe form of COVID-19 requiring ventilation in the intensive therapy unit,” said lead investigator Janaka Karalliedde, MBBS, PhD.

Dr. Karalliedde and colleagues note that this is “the first description of diabetic retinopathy as a potential risk factor for poor COVID-19 outcomes.”

“For this reason, looking for the presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe COVID-19,” added Dr. Karalliedde, of Guy’s and St Thomas’ NHS Foundation Trust, London.

The study was published online in Diabetes Research and Clinical Practice.
 

Preexisting diabetic retinopathy and COVID-19 outcomes

The prevalence of diabetic retinopathy is thought to be around 55% in people with type 1 diabetes and 30% in people with type 2 diabetes, on average.

Dr. Karalliedde is part of a research group at King’s College London that has been focused on how vascular disease may predispose to more severe COVID-19.

“COVID-19 affects the blood vessels all over the body,” he said, so they wondered whether having preexisting retinopathy “would predispose to a severe manifestation of COVID-19.”

The observational study included 187 patients with diabetes (179 patients with type 2 diabetes and 8 patients with type 1 diabetes) hospitalized with COVID-19 at Guy’s and St Thomas’ NHS Foundation Trust between March 12 and April 7 (the peak of the first wave of the pandemic in the United Kingdom).  

“It was an ethnically diverse population who were very sick and provides a clinical observation of real life,” Dr. Karalliedde said.

Nearly half of patients were African Caribbean (44%), 39% were White, and 17% were of other ethnicities, including 8% who were Asian. The mean age of the cohort was 68 years (range, 22-97 years), and 60% were men.

Diabetic retinopathy was reported in 67 (36%) patients, of whom 80% had background retinopathy and 20% had more advanced retinopathy.

They then looked at whether the presence of retinopathy was associated with a more severe manifestation of COVID-19 as defined by the need for tracheal intubation.

Of the 187 patients, 26% were intubated and 45% of these patients had diabetic retinopathy.

The analysis showed those with diabetic retinopathy had an over-fivefold increased risk for intubation (odds ratio, 5.81; 95% confidence interval, 1.37-24.66).

Of the entire cohort, 32% of patients died, although no association was observed between retinopathy and mortality.

“A greater number of diabetes patients with COVID-19 ended up on the intensive therapy unit. Upon multivariate analysis, we found retinopathy was independently associated with ending up on the intensive therapy unit,” stressed Dr. Karalliedde.

However, they noted that, “due to the cross-sectional design of our study, we cannot prove causality [between retinopathy and intubation]. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.”

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

Risk of intubation for COVID-19 in very sick hospitalized patients was increased over fivefold in those with diabetic retinopathy, compared with those without, in a small single-center study from the United Kingdom.

Importantly, the risk of intubation was independent of conventional risk factors for poor COVID-19 outcomes.

“People with preexisting diabetes-related vascular damage, such as retinopathy, might be predisposed to a more severe form of COVID-19 requiring ventilation in the intensive therapy unit,” said lead investigator Janaka Karalliedde, MBBS, PhD.

Dr. Karalliedde and colleagues note that this is “the first description of diabetic retinopathy as a potential risk factor for poor COVID-19 outcomes.”

“For this reason, looking for the presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe COVID-19,” added Dr. Karalliedde, of Guy’s and St Thomas’ NHS Foundation Trust, London.

The study was published online in Diabetes Research and Clinical Practice.
 

Preexisting diabetic retinopathy and COVID-19 outcomes

The prevalence of diabetic retinopathy is thought to be around 55% in people with type 1 diabetes and 30% in people with type 2 diabetes, on average.

Dr. Karalliedde is part of a research group at King’s College London that has been focused on how vascular disease may predispose to more severe COVID-19.

“COVID-19 affects the blood vessels all over the body,” he said, so they wondered whether having preexisting retinopathy “would predispose to a severe manifestation of COVID-19.”

The observational study included 187 patients with diabetes (179 patients with type 2 diabetes and 8 patients with type 1 diabetes) hospitalized with COVID-19 at Guy’s and St Thomas’ NHS Foundation Trust between March 12 and April 7 (the peak of the first wave of the pandemic in the United Kingdom).  

“It was an ethnically diverse population who were very sick and provides a clinical observation of real life,” Dr. Karalliedde said.

Nearly half of patients were African Caribbean (44%), 39% were White, and 17% were of other ethnicities, including 8% who were Asian. The mean age of the cohort was 68 years (range, 22-97 years), and 60% were men.

Diabetic retinopathy was reported in 67 (36%) patients, of whom 80% had background retinopathy and 20% had more advanced retinopathy.

They then looked at whether the presence of retinopathy was associated with a more severe manifestation of COVID-19 as defined by the need for tracheal intubation.

Of the 187 patients, 26% were intubated and 45% of these patients had diabetic retinopathy.

The analysis showed those with diabetic retinopathy had an over-fivefold increased risk for intubation (odds ratio, 5.81; 95% confidence interval, 1.37-24.66).

Of the entire cohort, 32% of patients died, although no association was observed between retinopathy and mortality.

“A greater number of diabetes patients with COVID-19 ended up on the intensive therapy unit. Upon multivariate analysis, we found retinopathy was independently associated with ending up on the intensive therapy unit,” stressed Dr. Karalliedde.

However, they noted that, “due to the cross-sectional design of our study, we cannot prove causality [between retinopathy and intubation]. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.”

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

Risk of intubation for COVID-19 in very sick hospitalized patients was increased over fivefold in those with diabetic retinopathy, compared with those without, in a small single-center study from the United Kingdom.

Importantly, the risk of intubation was independent of conventional risk factors for poor COVID-19 outcomes.

“People with preexisting diabetes-related vascular damage, such as retinopathy, might be predisposed to a more severe form of COVID-19 requiring ventilation in the intensive therapy unit,” said lead investigator Janaka Karalliedde, MBBS, PhD.

Dr. Karalliedde and colleagues note that this is “the first description of diabetic retinopathy as a potential risk factor for poor COVID-19 outcomes.”

“For this reason, looking for the presence or history of retinopathy or other vascular complications of diabetes may help health care professionals identify patients at high risk of severe COVID-19,” added Dr. Karalliedde, of Guy’s and St Thomas’ NHS Foundation Trust, London.

The study was published online in Diabetes Research and Clinical Practice.
 

Preexisting diabetic retinopathy and COVID-19 outcomes

The prevalence of diabetic retinopathy is thought to be around 55% in people with type 1 diabetes and 30% in people with type 2 diabetes, on average.

Dr. Karalliedde is part of a research group at King’s College London that has been focused on how vascular disease may predispose to more severe COVID-19.

“COVID-19 affects the blood vessels all over the body,” he said, so they wondered whether having preexisting retinopathy “would predispose to a severe manifestation of COVID-19.”

The observational study included 187 patients with diabetes (179 patients with type 2 diabetes and 8 patients with type 1 diabetes) hospitalized with COVID-19 at Guy’s and St Thomas’ NHS Foundation Trust between March 12 and April 7 (the peak of the first wave of the pandemic in the United Kingdom).  

“It was an ethnically diverse population who were very sick and provides a clinical observation of real life,” Dr. Karalliedde said.

Nearly half of patients were African Caribbean (44%), 39% were White, and 17% were of other ethnicities, including 8% who were Asian. The mean age of the cohort was 68 years (range, 22-97 years), and 60% were men.

Diabetic retinopathy was reported in 67 (36%) patients, of whom 80% had background retinopathy and 20% had more advanced retinopathy.

They then looked at whether the presence of retinopathy was associated with a more severe manifestation of COVID-19 as defined by the need for tracheal intubation.

Of the 187 patients, 26% were intubated and 45% of these patients had diabetic retinopathy.

The analysis showed those with diabetic retinopathy had an over-fivefold increased risk for intubation (odds ratio, 5.81; 95% confidence interval, 1.37-24.66).

Of the entire cohort, 32% of patients died, although no association was observed between retinopathy and mortality.

“A greater number of diabetes patients with COVID-19 ended up on the intensive therapy unit. Upon multivariate analysis, we found retinopathy was independently associated with ending up on the intensive therapy unit,” stressed Dr. Karalliedde.

However, they noted that, “due to the cross-sectional design of our study, we cannot prove causality [between retinopathy and intubation]. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.”

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

Home administration of bortezomib (Velcade), as a once or twice-weekly subcutaneous self-injection is safe in patients with myeloma, significantly reducing hospital visits, and likely improving quality of life, a study shows.

The majority (43 of 52 patients) successfully self-administered bortezomib and completed the course. Also, hospital visits for those on the so-called Homecare programme reduced by 50%, with most visits comprising a fortnightly drug pickup from the drive-through pharmacy.

The work was presented as a poster by lead author and researcher, Kanchana De Abrew, hematology consultant at University Hospital Southampton NHS Foundation Trust, at this year’s virtual British Society of Haematology (BSH) meeting. De Abrew conducted the study while at Queen Alexandra Hospital, Portsmouth.

“We wanted to minimize patient visits to hospital because with travel time and waiting time, patients can easily find a visit takes up a whole morning, so this relates to their quality of life as well as having financial implications for patients,” Dr. De Abrew said in an interview. It also reduced the impact on day units and improved capacity for other services.

Dr. De Abrew noted that the study was conducted in the pre-COVID-19 era, but that the current enhanced threat of infection only served to reinforce the benefits of self-administration at home and avoiding unnecessary hospital visits.

“This project could easily be set up in other hospitals and some other centers have already contacted us about this. It might suit rural areas,” she added.
 

‘Safe and effective’

Dr. Matthew Jenner, consultant hematologist for University Hospital Southampton NHS Foundation Trust, who was not involved in the study, remarked that the study demonstrated another way to deliver bortezomib outside of hospital in addition to home care services that require trained nurses to administer treatment. “With a modest amount of training of the patient and family, it is both a safe and effective way of delivering treatment. This reduces hospital visits for the patient and frees up much needed capacity for heavily stretched chemotherapy units, creating space for other newer treatments that require hospital attendance.

“It is of benefit all round to both the patients undertaking self-administration and those who benefit from improved capacity,” added Dr. Jenner.
 

Avoiding hospital visits

Myeloma patients are already immunosuppressed prior to treatment and then this worsens once on treatment. Once they are sitting in a clinic environment they are surrounded by similarly immunosuppressed patients, so their risk is heightened further.

Figures suggest myeloma cases are on the increase. Annually, the United Kingdom sees around 5,800 new cases of myeloma and incidence increased by a significant 32% between the periods of 1993-1995 and 2015-2017. These figures were reflected in the patient numbers at the Queen Alexandra Hospital where the study was carried out. Many patients receive bortezomib, which forms the backbone of four National Institute for Health and Care Excellence (NICE) approved regimens.

“Patients are living longer so in the early 2000s patients had a life expectancy of 2-3 years, whereas now patients live for around 5 years. Also, the scope and lines of treatments have increased a lot. Over 50% of patients are likely to have bortezomib at some point in their management,” explained Dr. De Abrew.

Bortezomib is given once or twice weekly as a subcutaneous injection, and this usually continues for approximately 6-8 months with four to six cycles. Administering the drug in hospital requires around a half-hour slot placing considerable burden on the hematology day unit resources, and this can adversely affect the patient experience with waiting times and the need for frequent hospital visits.
 

Patient or relatives taught to self-administer at home

In 2017, clinical nurse specialists taught suitable patients to self-administer bortezomib in the Homecare protocol. Patients collected a 2-week supply of the drug. The protocol aimed to improve patient quality of life by reducing hospital visits, and increasing capacity in the hematology day unit. Since the start of the programme in 2017, the majority (71) of myeloma patients at Portsmouth have been treated through the Homecare program.

Dr. De Abrew conducted a retrospective review of patients who received bortezomib between January and October 2019 aimed at determining the effectiveness of the Homecare programme. To this end, she measured the proportion able to commence the Homecare protocol; the proportion successful in completing treatment on the Homecare protocol; the amount of additional clinical nurse specialist time required to support the Homecare protocol; and the number of associated adverse incidents.

A total of 52 bortezomib-treated patients were included in the study. Patients were excluded if they were on a different combination of drugs that required hospital visits, or inpatient care for other reasons. Three patients ceased the drug – two because of toxicity, and one because of rapid progression.  The average age of patients was 74 years, and 55.8% were using bortezomib as first-line, 36.5% second-line, and the remainder third-line or more.

The vast majority started the Homecare protocol (45/52), and 25 self-administered and 17 received a relative’s help. A total of 43 completed the self-administration protocol with two reverting to hospital assistance. Bortezomib was given for four to six cycles lasting around 6-8 months.

Clinical nurse specialists trained 38 patients for home care, with an average training time of 43 minutes. Two of these patients were considered unsuitable for self-administration. The remainder were trained by ward nurses or did not require training having received bortezomib previously.

A total of 20 patients required additional clinical nurse specialist time requiring an average of 55 minutes. Of those requiring additional support: Seven needed retraining; two needed the first dose delivered by a nurse specialist; two requested help from the hematology unit; and nine wanted general extra support – for example, help with injection site queries (usually administered to the abdominal area), reassurance during administration, syringe queries, administrative queries, and queries around spillages.

“Importantly, patients always have the phone number of the nurse specialist at hand. But most people managed okay, and even if they needed additional support they still got there,” remarked Dr. De Abrew.

In terms of adverse events, there were six in total. These included three reported spillages (with no harm caused), and three experienced injection site incidents (rash, pain). “We found a low number of reported adverse events,” she said.

Dr. De Abrew added that generally, many more medications were being converted to subcutaneous formulations in myeloma and other hematology conditions. “Perhaps these results could inform self-administration of other drugs. In hematology, we get so many new drugs come through every year, but we don’t get the increased resources to manage this in the day units. Broadening self-administration could really help with capacity as well as improve quality of life for the patients.

“These results show that it can be done!” she said. 

Dr. De Abrew declared no relevant conflicts of interest. Dr. Jenner declared receiving honoraria from Janssen, which manufactures branded Velcade (bortezomib).

A version of this story originally appeared on Medscape.com.

Home administration of bortezomib (Velcade), as a once or twice-weekly subcutaneous self-injection is safe in patients with myeloma, significantly reducing hospital visits, and likely improving quality of life, a study shows.

The majority (43 of 52 patients) successfully self-administered bortezomib and completed the course. Also, hospital visits for those on the so-called Homecare programme reduced by 50%, with most visits comprising a fortnightly drug pickup from the drive-through pharmacy.

The work was presented as a poster by lead author and researcher, Kanchana De Abrew, hematology consultant at University Hospital Southampton NHS Foundation Trust, at this year’s virtual British Society of Haematology (BSH) meeting. De Abrew conducted the study while at Queen Alexandra Hospital, Portsmouth.

“We wanted to minimize patient visits to hospital because with travel time and waiting time, patients can easily find a visit takes up a whole morning, so this relates to their quality of life as well as having financial implications for patients,” Dr. De Abrew said in an interview. It also reduced the impact on day units and improved capacity for other services.

Dr. De Abrew noted that the study was conducted in the pre-COVID-19 era, but that the current enhanced threat of infection only served to reinforce the benefits of self-administration at home and avoiding unnecessary hospital visits.

“This project could easily be set up in other hospitals and some other centers have already contacted us about this. It might suit rural areas,” she added.
 

‘Safe and effective’

Dr. Matthew Jenner, consultant hematologist for University Hospital Southampton NHS Foundation Trust, who was not involved in the study, remarked that the study demonstrated another way to deliver bortezomib outside of hospital in addition to home care services that require trained nurses to administer treatment. “With a modest amount of training of the patient and family, it is both a safe and effective way of delivering treatment. This reduces hospital visits for the patient and frees up much needed capacity for heavily stretched chemotherapy units, creating space for other newer treatments that require hospital attendance.

“It is of benefit all round to both the patients undertaking self-administration and those who benefit from improved capacity,” added Dr. Jenner.
 

Avoiding hospital visits

Myeloma patients are already immunosuppressed prior to treatment and then this worsens once on treatment. Once they are sitting in a clinic environment they are surrounded by similarly immunosuppressed patients, so their risk is heightened further.

Figures suggest myeloma cases are on the increase. Annually, the United Kingdom sees around 5,800 new cases of myeloma and incidence increased by a significant 32% between the periods of 1993-1995 and 2015-2017. These figures were reflected in the patient numbers at the Queen Alexandra Hospital where the study was carried out. Many patients receive bortezomib, which forms the backbone of four National Institute for Health and Care Excellence (NICE) approved regimens.

“Patients are living longer so in the early 2000s patients had a life expectancy of 2-3 years, whereas now patients live for around 5 years. Also, the scope and lines of treatments have increased a lot. Over 50% of patients are likely to have bortezomib at some point in their management,” explained Dr. De Abrew.

Bortezomib is given once or twice weekly as a subcutaneous injection, and this usually continues for approximately 6-8 months with four to six cycles. Administering the drug in hospital requires around a half-hour slot placing considerable burden on the hematology day unit resources, and this can adversely affect the patient experience with waiting times and the need for frequent hospital visits.
 

Patient or relatives taught to self-administer at home

In 2017, clinical nurse specialists taught suitable patients to self-administer bortezomib in the Homecare protocol. Patients collected a 2-week supply of the drug. The protocol aimed to improve patient quality of life by reducing hospital visits, and increasing capacity in the hematology day unit. Since the start of the programme in 2017, the majority (71) of myeloma patients at Portsmouth have been treated through the Homecare program.

Dr. De Abrew conducted a retrospective review of patients who received bortezomib between January and October 2019 aimed at determining the effectiveness of the Homecare programme. To this end, she measured the proportion able to commence the Homecare protocol; the proportion successful in completing treatment on the Homecare protocol; the amount of additional clinical nurse specialist time required to support the Homecare protocol; and the number of associated adverse incidents.

A total of 52 bortezomib-treated patients were included in the study. Patients were excluded if they were on a different combination of drugs that required hospital visits, or inpatient care for other reasons. Three patients ceased the drug – two because of toxicity, and one because of rapid progression.  The average age of patients was 74 years, and 55.8% were using bortezomib as first-line, 36.5% second-line, and the remainder third-line or more.

The vast majority started the Homecare protocol (45/52), and 25 self-administered and 17 received a relative’s help. A total of 43 completed the self-administration protocol with two reverting to hospital assistance. Bortezomib was given for four to six cycles lasting around 6-8 months.

Clinical nurse specialists trained 38 patients for home care, with an average training time of 43 minutes. Two of these patients were considered unsuitable for self-administration. The remainder were trained by ward nurses or did not require training having received bortezomib previously.

A total of 20 patients required additional clinical nurse specialist time requiring an average of 55 minutes. Of those requiring additional support: Seven needed retraining; two needed the first dose delivered by a nurse specialist; two requested help from the hematology unit; and nine wanted general extra support – for example, help with injection site queries (usually administered to the abdominal area), reassurance during administration, syringe queries, administrative queries, and queries around spillages.

“Importantly, patients always have the phone number of the nurse specialist at hand. But most people managed okay, and even if they needed additional support they still got there,” remarked Dr. De Abrew.

In terms of adverse events, there were six in total. These included three reported spillages (with no harm caused), and three experienced injection site incidents (rash, pain). “We found a low number of reported adverse events,” she said.

Dr. De Abrew added that generally, many more medications were being converted to subcutaneous formulations in myeloma and other hematology conditions. “Perhaps these results could inform self-administration of other drugs. In hematology, we get so many new drugs come through every year, but we don’t get the increased resources to manage this in the day units. Broadening self-administration could really help with capacity as well as improve quality of life for the patients.

“These results show that it can be done!” she said. 

Dr. De Abrew declared no relevant conflicts of interest. Dr. Jenner declared receiving honoraria from Janssen, which manufactures branded Velcade (bortezomib).

A version of this story originally appeared on Medscape.com.

Home administration of bortezomib (Velcade), as a once or twice-weekly subcutaneous self-injection is safe in patients with myeloma, significantly reducing hospital visits, and likely improving quality of life, a study shows.

The majority (43 of 52 patients) successfully self-administered bortezomib and completed the course. Also, hospital visits for those on the so-called Homecare programme reduced by 50%, with most visits comprising a fortnightly drug pickup from the drive-through pharmacy.

The work was presented as a poster by lead author and researcher, Kanchana De Abrew, hematology consultant at University Hospital Southampton NHS Foundation Trust, at this year’s virtual British Society of Haematology (BSH) meeting. De Abrew conducted the study while at Queen Alexandra Hospital, Portsmouth.

“We wanted to minimize patient visits to hospital because with travel time and waiting time, patients can easily find a visit takes up a whole morning, so this relates to their quality of life as well as having financial implications for patients,” Dr. De Abrew said in an interview. It also reduced the impact on day units and improved capacity for other services.

Dr. De Abrew noted that the study was conducted in the pre-COVID-19 era, but that the current enhanced threat of infection only served to reinforce the benefits of self-administration at home and avoiding unnecessary hospital visits.

“This project could easily be set up in other hospitals and some other centers have already contacted us about this. It might suit rural areas,” she added.
 

‘Safe and effective’

Dr. Matthew Jenner, consultant hematologist for University Hospital Southampton NHS Foundation Trust, who was not involved in the study, remarked that the study demonstrated another way to deliver bortezomib outside of hospital in addition to home care services that require trained nurses to administer treatment. “With a modest amount of training of the patient and family, it is both a safe and effective way of delivering treatment. This reduces hospital visits for the patient and frees up much needed capacity for heavily stretched chemotherapy units, creating space for other newer treatments that require hospital attendance.

“It is of benefit all round to both the patients undertaking self-administration and those who benefit from improved capacity,” added Dr. Jenner.
 

Avoiding hospital visits

Myeloma patients are already immunosuppressed prior to treatment and then this worsens once on treatment. Once they are sitting in a clinic environment they are surrounded by similarly immunosuppressed patients, so their risk is heightened further.

Figures suggest myeloma cases are on the increase. Annually, the United Kingdom sees around 5,800 new cases of myeloma and incidence increased by a significant 32% between the periods of 1993-1995 and 2015-2017. These figures were reflected in the patient numbers at the Queen Alexandra Hospital where the study was carried out. Many patients receive bortezomib, which forms the backbone of four National Institute for Health and Care Excellence (NICE) approved regimens.

“Patients are living longer so in the early 2000s patients had a life expectancy of 2-3 years, whereas now patients live for around 5 years. Also, the scope and lines of treatments have increased a lot. Over 50% of patients are likely to have bortezomib at some point in their management,” explained Dr. De Abrew.

Bortezomib is given once or twice weekly as a subcutaneous injection, and this usually continues for approximately 6-8 months with four to six cycles. Administering the drug in hospital requires around a half-hour slot placing considerable burden on the hematology day unit resources, and this can adversely affect the patient experience with waiting times and the need for frequent hospital visits.
 

Patient or relatives taught to self-administer at home

In 2017, clinical nurse specialists taught suitable patients to self-administer bortezomib in the Homecare protocol. Patients collected a 2-week supply of the drug. The protocol aimed to improve patient quality of life by reducing hospital visits, and increasing capacity in the hematology day unit. Since the start of the programme in 2017, the majority (71) of myeloma patients at Portsmouth have been treated through the Homecare program.

Dr. De Abrew conducted a retrospective review of patients who received bortezomib between January and October 2019 aimed at determining the effectiveness of the Homecare programme. To this end, she measured the proportion able to commence the Homecare protocol; the proportion successful in completing treatment on the Homecare protocol; the amount of additional clinical nurse specialist time required to support the Homecare protocol; and the number of associated adverse incidents.

A total of 52 bortezomib-treated patients were included in the study. Patients were excluded if they were on a different combination of drugs that required hospital visits, or inpatient care for other reasons. Three patients ceased the drug – two because of toxicity, and one because of rapid progression.  The average age of patients was 74 years, and 55.8% were using bortezomib as first-line, 36.5% second-line, and the remainder third-line or more.

The vast majority started the Homecare protocol (45/52), and 25 self-administered and 17 received a relative’s help. A total of 43 completed the self-administration protocol with two reverting to hospital assistance. Bortezomib was given for four to six cycles lasting around 6-8 months.

Clinical nurse specialists trained 38 patients for home care, with an average training time of 43 minutes. Two of these patients were considered unsuitable for self-administration. The remainder were trained by ward nurses or did not require training having received bortezomib previously.

A total of 20 patients required additional clinical nurse specialist time requiring an average of 55 minutes. Of those requiring additional support: Seven needed retraining; two needed the first dose delivered by a nurse specialist; two requested help from the hematology unit; and nine wanted general extra support – for example, help with injection site queries (usually administered to the abdominal area), reassurance during administration, syringe queries, administrative queries, and queries around spillages.

“Importantly, patients always have the phone number of the nurse specialist at hand. But most people managed okay, and even if they needed additional support they still got there,” remarked Dr. De Abrew.

In terms of adverse events, there were six in total. These included three reported spillages (with no harm caused), and three experienced injection site incidents (rash, pain). “We found a low number of reported adverse events,” she said.

Dr. De Abrew added that generally, many more medications were being converted to subcutaneous formulations in myeloma and other hematology conditions. “Perhaps these results could inform self-administration of other drugs. In hematology, we get so many new drugs come through every year, but we don’t get the increased resources to manage this in the day units. Broadening self-administration could really help with capacity as well as improve quality of life for the patients.

“These results show that it can be done!” she said. 

Dr. De Abrew declared no relevant conflicts of interest. Dr. Jenner declared receiving honoraria from Janssen, which manufactures branded Velcade (bortezomib).

A version of this story originally appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.

Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.

Christiane Haase, PhD, of Novo Nordisk, led the work together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.

“This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It’s extraordinary,” Dr. Finer asserted.

“These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously,” he added.

The size of the study, of over 550,000 U.K. adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity.

“Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions,” Dr. Haase said in an interview.

Carel Le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, welcomed the study because it showed those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.

“In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity,” he highlighted.

From a clinician standpoint, “it helps to consider all the weight-loss options available, but also for those who are not able to achieve weight-loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments,” he added.

Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: “It’s helpful to have further evidence that weight loss reduces risk for type 2 diabetes.”

However, “finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge,” he observed.
 

Large database of half a million people with obesity

For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink database, which holds information from 674 general practices in the United Kingdom, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.

At baseline, characteristics for the full study population included a median age of 54 years, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index (BMI) of 25.0-50.0 kg/m² at the start of the follow-up, between January 2001 and December 2010.

Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietitian. Some had been prescribed antiobesity medications available between 2001 and 2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.

“This is typical of real-world management of obesity,” Dr. Haase pointed out.

Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to 5%) and one who lost weight (60,573 with BMI change –10% to –25%).

The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.

The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 (obesity class I level); from 40.3 to 35 (obesity class II level), and from46 to 40 (obesity class III level).

Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.

Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.
 

Type 2 diabetes, sleep apnea showed greatest risk reductions

The researchers looked at the risk reduction for various comorbidities after weight loss, compared with before weight loss. They also examined the risk reductions after weight loss, compared with someone who had always had a median 13% lower weight.

Effectively, the analysis provided a measure of the effect of risk reduction because of weight loss, compared with having that lower weight as a stable weight.

“The analysis asks if the person’s risk was reversed by the weight loss to the risk associated with that of the lower weight level,” explained Dr. Haase.

“We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk,” she added.

With sleep apnea there was a risk reduction of up to 27%, compared with before weight loss.

“This is a condition that can’t be easily reversed except with mechanical sleeping devices and it is underrecognized and causes a lot of distress. There’s actually a link between sleep apnea, diabetes, and hypertension in a two-way connection,” noted Dr. Finer, who is also honorary professor of cardiovascular medicine at University College London.

“A reduction of this proportion is impressive,” he stressed.

Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. “We did not see any impact on myocardial infarction,” which “might be due to length of follow-up,” noted Dr. Haase.
 

Response of type 2 diabetes to weight loss

Most patients in the study did not have type 2 diabetes at baseline, and Dr. Finer commented on how weight loss might affect type 2 diabetes risk.

“The complications of obesity resolve with weight loss at different speeds,” he said.

“Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months.”

In contrast, reductions in risk of obstructive sleep apnea “take longer and might depend on the amount of weight lost.” And with osteoarthritis, “It’s hard to show improvement with weight loss because irreparable damage has [already] been done,” he explained.

The degree of improvement in diabetes because of weight loss is partly dependent on how long the person has had diabetes, Dr. Finer further explained. “If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater.”

Lucy Chambers, PhD, head of research communications at Diabetes UK, said: “We’ve known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk.”

She acknowledged, however, that losing weight is difficult and that support is important: “We need government to urgently review provision of weight management services and take action to address the barriers to accessing them.”

Dr. Finer and Dr. Haase are both employees of Novo Nordisk. Dr. Le Roux reported no relevant financial relationships.

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

Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.

Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.

Christiane Haase, PhD, of Novo Nordisk, led the work together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.

“This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It’s extraordinary,” Dr. Finer asserted.

“These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously,” he added.

The size of the study, of over 550,000 U.K. adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity.

“Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions,” Dr. Haase said in an interview.

Carel Le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, welcomed the study because it showed those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.

“In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity,” he highlighted.

From a clinician standpoint, “it helps to consider all the weight-loss options available, but also for those who are not able to achieve weight-loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments,” he added.

Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: “It’s helpful to have further evidence that weight loss reduces risk for type 2 diabetes.”

However, “finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge,” he observed.
 

Large database of half a million people with obesity

For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink database, which holds information from 674 general practices in the United Kingdom, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.

At baseline, characteristics for the full study population included a median age of 54 years, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index (BMI) of 25.0-50.0 kg/m² at the start of the follow-up, between January 2001 and December 2010.

Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietitian. Some had been prescribed antiobesity medications available between 2001 and 2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.

“This is typical of real-world management of obesity,” Dr. Haase pointed out.

Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to 5%) and one who lost weight (60,573 with BMI change –10% to –25%).

The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.

The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 (obesity class I level); from 40.3 to 35 (obesity class II level), and from46 to 40 (obesity class III level).

Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.

Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.
 

Type 2 diabetes, sleep apnea showed greatest risk reductions

The researchers looked at the risk reduction for various comorbidities after weight loss, compared with before weight loss. They also examined the risk reductions after weight loss, compared with someone who had always had a median 13% lower weight.

Effectively, the analysis provided a measure of the effect of risk reduction because of weight loss, compared with having that lower weight as a stable weight.

“The analysis asks if the person’s risk was reversed by the weight loss to the risk associated with that of the lower weight level,” explained Dr. Haase.

“We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk,” she added.

With sleep apnea there was a risk reduction of up to 27%, compared with before weight loss.

“This is a condition that can’t be easily reversed except with mechanical sleeping devices and it is underrecognized and causes a lot of distress. There’s actually a link between sleep apnea, diabetes, and hypertension in a two-way connection,” noted Dr. Finer, who is also honorary professor of cardiovascular medicine at University College London.

“A reduction of this proportion is impressive,” he stressed.

Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. “We did not see any impact on myocardial infarction,” which “might be due to length of follow-up,” noted Dr. Haase.
 

Response of type 2 diabetes to weight loss

Most patients in the study did not have type 2 diabetes at baseline, and Dr. Finer commented on how weight loss might affect type 2 diabetes risk.

“The complications of obesity resolve with weight loss at different speeds,” he said.

“Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months.”

In contrast, reductions in risk of obstructive sleep apnea “take longer and might depend on the amount of weight lost.” And with osteoarthritis, “It’s hard to show improvement with weight loss because irreparable damage has [already] been done,” he explained.

The degree of improvement in diabetes because of weight loss is partly dependent on how long the person has had diabetes, Dr. Finer further explained. “If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater.”

Lucy Chambers, PhD, head of research communications at Diabetes UK, said: “We’ve known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk.”

She acknowledged, however, that losing weight is difficult and that support is important: “We need government to urgently review provision of weight management services and take action to address the barriers to accessing them.”

Dr. Finer and Dr. Haase are both employees of Novo Nordisk. Dr. Le Roux reported no relevant financial relationships.

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

Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.

Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.

Christiane Haase, PhD, of Novo Nordisk, led the work together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.

“This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It’s extraordinary,” Dr. Finer asserted.

“These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously,” he added.

The size of the study, of over 550,000 U.K. adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity.

“Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions,” Dr. Haase said in an interview.

Carel Le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, welcomed the study because it showed those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.

“In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity,” he highlighted.

From a clinician standpoint, “it helps to consider all the weight-loss options available, but also for those who are not able to achieve weight-loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments,” he added.

Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: “It’s helpful to have further evidence that weight loss reduces risk for type 2 diabetes.”

However, “finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge,” he observed.
 

Large database of half a million people with obesity

For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink database, which holds information from 674 general practices in the United Kingdom, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.

At baseline, characteristics for the full study population included a median age of 54 years, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index (BMI) of 25.0-50.0 kg/m² at the start of the follow-up, between January 2001 and December 2010.

Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietitian. Some had been prescribed antiobesity medications available between 2001 and 2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.

“This is typical of real-world management of obesity,” Dr. Haase pointed out.

Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to 5%) and one who lost weight (60,573 with BMI change –10% to –25%).

The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.

The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 (obesity class I level); from 40.3 to 35 (obesity class II level), and from46 to 40 (obesity class III level).

Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.

Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.
 

Type 2 diabetes, sleep apnea showed greatest risk reductions

The researchers looked at the risk reduction for various comorbidities after weight loss, compared with before weight loss. They also examined the risk reductions after weight loss, compared with someone who had always had a median 13% lower weight.

Effectively, the analysis provided a measure of the effect of risk reduction because of weight loss, compared with having that lower weight as a stable weight.

“The analysis asks if the person’s risk was reversed by the weight loss to the risk associated with that of the lower weight level,” explained Dr. Haase.

“We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk,” she added.

With sleep apnea there was a risk reduction of up to 27%, compared with before weight loss.

“This is a condition that can’t be easily reversed except with mechanical sleeping devices and it is underrecognized and causes a lot of distress. There’s actually a link between sleep apnea, diabetes, and hypertension in a two-way connection,” noted Dr. Finer, who is also honorary professor of cardiovascular medicine at University College London.

“A reduction of this proportion is impressive,” he stressed.

Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. “We did not see any impact on myocardial infarction,” which “might be due to length of follow-up,” noted Dr. Haase.
 

Response of type 2 diabetes to weight loss

Most patients in the study did not have type 2 diabetes at baseline, and Dr. Finer commented on how weight loss might affect type 2 diabetes risk.

“The complications of obesity resolve with weight loss at different speeds,” he said.

“Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months.”

In contrast, reductions in risk of obstructive sleep apnea “take longer and might depend on the amount of weight lost.” And with osteoarthritis, “It’s hard to show improvement with weight loss because irreparable damage has [already] been done,” he explained.

The degree of improvement in diabetes because of weight loss is partly dependent on how long the person has had diabetes, Dr. Finer further explained. “If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater.”

Lucy Chambers, PhD, head of research communications at Diabetes UK, said: “We’ve known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk.”

She acknowledged, however, that losing weight is difficult and that support is important: “We need government to urgently review provision of weight management services and take action to address the barriers to accessing them.”

Dr. Finer and Dr. Haase are both employees of Novo Nordisk. Dr. Le Roux reported no relevant financial relationships.

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

An online, lifestyle-based weight loss initiative known as the Balance After Baby (BAB) program is effective at reducing weight retention a year after birth among women with recent gestational diabetes.

Specifically, results of the study were positive in women of most ethnicities, bar those of a small group of Hispanic origin.

Jacinda Nicklas, MD, from the University of Colorado at Denver, Aurora, presented findings of the BAB trial during the virtual annual scientific sessions of the American Diabetes Association. She was coprincipal investigator alongside Ellen Seely, MD, from Brigham and Women’s Hospital, Boston.

“Looking at the entire population of women on the BAB program, there was a trend in weight loss from 6 weeks postpartum to 12 months (P = .09), and significantly less postpartum weight retention at 12 months (P = .04),” Dr. Nicklas said.

“Through this effect on postpartum weight retention, the BAB program has potential to delay or prevent development of type 2 diabetes in women with recent gestational diabetes, while the web-based, remote nature of the program is scalable and very relevant in current times,” she added. “However, the lack of efficacy in Hispanic women means it needs to be modified to be successful in this ethnic group.”

Frank Qian, MD, who also presented during the same session, said the BAB program has potential as a viable way of preventing both future pregnancy complications and the progression to overt type 2 diabetes in this high-risk population.

“Large-scale epidemiologic studies show us that weight gain from pregnancy is a major risk factor for long-term cardiometabolic risk, particularly for women with a history of gestational diabetes,” he observed. “In turn, it is critical to implement lifestyle interventions that can help women get as close to the weight they were before pregnancy as possible and keep that weight off.”
 

Postpartum weight retention a modifiable risk factor for type 2 diabetes

Current evidence shows that a large proportion of women who develop gestational diabetes go on to develop type 2 diabetes within 10 years and that women with a history of gestational diabetes are more likely to retain or gain weight postpartum.

Dr. Nicklas also pointed out that obesity and weight gain are the strongest modifiable risk factors for type 2 diabetes.

“We know from the Diabetes Prevention Program [DPP] that an intensive lifestyle program in women who had had gestational diabetes led to a 53% reduction in type 2 diabetes,” Dr. Nicklas noted.

However, she added there were barriers to adhering to the intensive DPP program – which required 16 one-on-one meetings in the first 24 weeks – including travel, as some participants lived quite remotely, or family responsibilities. Consequently, Dr. Nicklas and colleagues developed the BAB pilot trial, which involved web-based delivery with remote coaching.

The trial involved women with a history of gestational diabetes who were, on average, 7 weeks postpartum. The key outcome was weight at 12 months, compared with both 6-week postpartum weight and prepregnancy weight.

Based on encouraging results in the pilot trial – in which the intervention group showed significant weight loss from 6-week postpartum weight and in 12-month weight retention – a larger, two-site trial was initiated, the BAB Intervention randomized, controlled trial.

Outcome measures were the same as for the pilot study. The 181 participants were aged 18-45 years, had recent gestational diabetes, and had a mean prepregnancy body mass index of approximately 29 kg/m². Around half were college educated, and 28% were from lower income households. Overall, 48% were white, 22% Asian, 17% African American, and 13% were of other ethnicities, with just over a third being Hispanic.

The initial study visit was at 6 weeks postpartum. Women were randomized to the behavioral intervention website plus a lifestyle coach group or to a control group that consisted of a website plus knowledge links.

The intervention website required women to complete some DPP-derived and bonus modules, and also featured action plans, tracked weight and steps, and had a direct link to contact their lifestyle coach. Follow-up visits were held at 6 and 12 months and A1c, waist circumference, and height/weight were measured. A total of 86% eligible women completed the 6- and 12-month visits.

Why didn’t the BAB program work in Hispanic women?

“The overall result showed that weight change from 6 weeks postpartum to 12 months revealed a slight gain in the control group of 1.3 pounds and a loss in the intervention group of 1.8 pounds, resulting in a between-group difference of 3.1 pounds [P = .09],” reported Dr. Nicklas. Adjustment for gestational weight gain and breastfeeding had no substantial effect.

When 12-month weight retention versus prepregnancy weight was assessed, the former was halved in participants in the BAB program.

The control group gained a mean of 10.1 pounds, and those in the intervention group gained a mean of 5.3 pounds, equivalent to a difference of 4.8 pounds (P = .04).

A prespecified analysis was conducted of 120 non-Hispanic women. At 12 months, weight retention, compared with prepregnancy weight showed an increase of 9 pounds in the control group versus 1.8 pounds in the intervention group (P = .01).

By comparison, in the small group of Hispanic women only, weight retention at 12 months compared to prepregnancy weight showed a 12.7-pound increase and a 13.3-pound increase in the control and intervention groups respectively, reported Dr. Nicklas.

Addressing the key question of why the BAB program was ineffective in Hispanic women, Dr. Nicklas said, “The literature tells us that low income Hispanic women are twice as likely to experience postpartum weight retention compared to white non-Hispanic women. But we also know that low-income Hispanic women generally engage less with interventions, and there is a higher acceptance of overweight among this ethnic group.”

The researchers hope to follow the women from their trial to determine who progresses to type 2 diabetes.

“Hispanic women are a high-risk population for gestational diabetes and type 2 diabetes, and we plan to identify the best options to help Hispanic women with a history of gestational diabetes prevent type 2 diabetes,” Dr. Nicklas said in an interview.

Dr. Qian also remarked on the differences observed in the weight loss outcomes for non-Hispanic versus Hispanic women, noting that it highlights the importance of studying lifestyle interventions in diverse populations. “Environmental and cultural factors that may differ across different racial or ethnic groups could impact the effectiveness of such interventions.

Dr. Nicklas and Dr. Qian have reported no relevant financial relationships.

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

An online, lifestyle-based weight loss initiative known as the Balance After Baby (BAB) program is effective at reducing weight retention a year after birth among women with recent gestational diabetes.

Specifically, results of the study were positive in women of most ethnicities, bar those of a small group of Hispanic origin.

Jacinda Nicklas, MD, from the University of Colorado at Denver, Aurora, presented findings of the BAB trial during the virtual annual scientific sessions of the American Diabetes Association. She was coprincipal investigator alongside Ellen Seely, MD, from Brigham and Women’s Hospital, Boston.

“Looking at the entire population of women on the BAB program, there was a trend in weight loss from 6 weeks postpartum to 12 months (P = .09), and significantly less postpartum weight retention at 12 months (P = .04),” Dr. Nicklas said.

“Through this effect on postpartum weight retention, the BAB program has potential to delay or prevent development of type 2 diabetes in women with recent gestational diabetes, while the web-based, remote nature of the program is scalable and very relevant in current times,” she added. “However, the lack of efficacy in Hispanic women means it needs to be modified to be successful in this ethnic group.”

Frank Qian, MD, who also presented during the same session, said the BAB program has potential as a viable way of preventing both future pregnancy complications and the progression to overt type 2 diabetes in this high-risk population.

“Large-scale epidemiologic studies show us that weight gain from pregnancy is a major risk factor for long-term cardiometabolic risk, particularly for women with a history of gestational diabetes,” he observed. “In turn, it is critical to implement lifestyle interventions that can help women get as close to the weight they were before pregnancy as possible and keep that weight off.”
 

Postpartum weight retention a modifiable risk factor for type 2 diabetes

Current evidence shows that a large proportion of women who develop gestational diabetes go on to develop type 2 diabetes within 10 years and that women with a history of gestational diabetes are more likely to retain or gain weight postpartum.

Dr. Nicklas also pointed out that obesity and weight gain are the strongest modifiable risk factors for type 2 diabetes.

“We know from the Diabetes Prevention Program [DPP] that an intensive lifestyle program in women who had had gestational diabetes led to a 53% reduction in type 2 diabetes,” Dr. Nicklas noted.

However, she added there were barriers to adhering to the intensive DPP program – which required 16 one-on-one meetings in the first 24 weeks – including travel, as some participants lived quite remotely, or family responsibilities. Consequently, Dr. Nicklas and colleagues developed the BAB pilot trial, which involved web-based delivery with remote coaching.

The trial involved women with a history of gestational diabetes who were, on average, 7 weeks postpartum. The key outcome was weight at 12 months, compared with both 6-week postpartum weight and prepregnancy weight.

Based on encouraging results in the pilot trial – in which the intervention group showed significant weight loss from 6-week postpartum weight and in 12-month weight retention – a larger, two-site trial was initiated, the BAB Intervention randomized, controlled trial.

Outcome measures were the same as for the pilot study. The 181 participants were aged 18-45 years, had recent gestational diabetes, and had a mean prepregnancy body mass index of approximately 29 kg/m². Around half were college educated, and 28% were from lower income households. Overall, 48% were white, 22% Asian, 17% African American, and 13% were of other ethnicities, with just over a third being Hispanic.

The initial study visit was at 6 weeks postpartum. Women were randomized to the behavioral intervention website plus a lifestyle coach group or to a control group that consisted of a website plus knowledge links.

The intervention website required women to complete some DPP-derived and bonus modules, and also featured action plans, tracked weight and steps, and had a direct link to contact their lifestyle coach. Follow-up visits were held at 6 and 12 months and A1c, waist circumference, and height/weight were measured. A total of 86% eligible women completed the 6- and 12-month visits.

Why didn’t the BAB program work in Hispanic women?

“The overall result showed that weight change from 6 weeks postpartum to 12 months revealed a slight gain in the control group of 1.3 pounds and a loss in the intervention group of 1.8 pounds, resulting in a between-group difference of 3.1 pounds [P = .09],” reported Dr. Nicklas. Adjustment for gestational weight gain and breastfeeding had no substantial effect.

When 12-month weight retention versus prepregnancy weight was assessed, the former was halved in participants in the BAB program.

The control group gained a mean of 10.1 pounds, and those in the intervention group gained a mean of 5.3 pounds, equivalent to a difference of 4.8 pounds (P = .04).

A prespecified analysis was conducted of 120 non-Hispanic women. At 12 months, weight retention, compared with prepregnancy weight showed an increase of 9 pounds in the control group versus 1.8 pounds in the intervention group (P = .01).

By comparison, in the small group of Hispanic women only, weight retention at 12 months compared to prepregnancy weight showed a 12.7-pound increase and a 13.3-pound increase in the control and intervention groups respectively, reported Dr. Nicklas.

Addressing the key question of why the BAB program was ineffective in Hispanic women, Dr. Nicklas said, “The literature tells us that low income Hispanic women are twice as likely to experience postpartum weight retention compared to white non-Hispanic women. But we also know that low-income Hispanic women generally engage less with interventions, and there is a higher acceptance of overweight among this ethnic group.”

The researchers hope to follow the women from their trial to determine who progresses to type 2 diabetes.

“Hispanic women are a high-risk population for gestational diabetes and type 2 diabetes, and we plan to identify the best options to help Hispanic women with a history of gestational diabetes prevent type 2 diabetes,” Dr. Nicklas said in an interview.

Dr. Qian also remarked on the differences observed in the weight loss outcomes for non-Hispanic versus Hispanic women, noting that it highlights the importance of studying lifestyle interventions in diverse populations. “Environmental and cultural factors that may differ across different racial or ethnic groups could impact the effectiveness of such interventions.

Dr. Nicklas and Dr. Qian have reported no relevant financial relationships.

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

An online, lifestyle-based weight loss initiative known as the Balance After Baby (BAB) program is effective at reducing weight retention a year after birth among women with recent gestational diabetes.

Specifically, results of the study were positive in women of most ethnicities, bar those of a small group of Hispanic origin.

Jacinda Nicklas, MD, from the University of Colorado at Denver, Aurora, presented findings of the BAB trial during the virtual annual scientific sessions of the American Diabetes Association. She was coprincipal investigator alongside Ellen Seely, MD, from Brigham and Women’s Hospital, Boston.

“Looking at the entire population of women on the BAB program, there was a trend in weight loss from 6 weeks postpartum to 12 months (P = .09), and significantly less postpartum weight retention at 12 months (P = .04),” Dr. Nicklas said.

“Through this effect on postpartum weight retention, the BAB program has potential to delay or prevent development of type 2 diabetes in women with recent gestational diabetes, while the web-based, remote nature of the program is scalable and very relevant in current times,” she added. “However, the lack of efficacy in Hispanic women means it needs to be modified to be successful in this ethnic group.”

Frank Qian, MD, who also presented during the same session, said the BAB program has potential as a viable way of preventing both future pregnancy complications and the progression to overt type 2 diabetes in this high-risk population.

“Large-scale epidemiologic studies show us that weight gain from pregnancy is a major risk factor for long-term cardiometabolic risk, particularly for women with a history of gestational diabetes,” he observed. “In turn, it is critical to implement lifestyle interventions that can help women get as close to the weight they were before pregnancy as possible and keep that weight off.”
 

Postpartum weight retention a modifiable risk factor for type 2 diabetes

Current evidence shows that a large proportion of women who develop gestational diabetes go on to develop type 2 diabetes within 10 years and that women with a history of gestational diabetes are more likely to retain or gain weight postpartum.

Dr. Nicklas also pointed out that obesity and weight gain are the strongest modifiable risk factors for type 2 diabetes.

“We know from the Diabetes Prevention Program [DPP] that an intensive lifestyle program in women who had had gestational diabetes led to a 53% reduction in type 2 diabetes,” Dr. Nicklas noted.

However, she added there were barriers to adhering to the intensive DPP program – which required 16 one-on-one meetings in the first 24 weeks – including travel, as some participants lived quite remotely, or family responsibilities. Consequently, Dr. Nicklas and colleagues developed the BAB pilot trial, which involved web-based delivery with remote coaching.

The trial involved women with a history of gestational diabetes who were, on average, 7 weeks postpartum. The key outcome was weight at 12 months, compared with both 6-week postpartum weight and prepregnancy weight.

Based on encouraging results in the pilot trial – in which the intervention group showed significant weight loss from 6-week postpartum weight and in 12-month weight retention – a larger, two-site trial was initiated, the BAB Intervention randomized, controlled trial.

Outcome measures were the same as for the pilot study. The 181 participants were aged 18-45 years, had recent gestational diabetes, and had a mean prepregnancy body mass index of approximately 29 kg/m². Around half were college educated, and 28% were from lower income households. Overall, 48% were white, 22% Asian, 17% African American, and 13% were of other ethnicities, with just over a third being Hispanic.

The initial study visit was at 6 weeks postpartum. Women were randomized to the behavioral intervention website plus a lifestyle coach group or to a control group that consisted of a website plus knowledge links.

The intervention website required women to complete some DPP-derived and bonus modules, and also featured action plans, tracked weight and steps, and had a direct link to contact their lifestyle coach. Follow-up visits were held at 6 and 12 months and A1c, waist circumference, and height/weight were measured. A total of 86% eligible women completed the 6- and 12-month visits.

Why didn’t the BAB program work in Hispanic women?

“The overall result showed that weight change from 6 weeks postpartum to 12 months revealed a slight gain in the control group of 1.3 pounds and a loss in the intervention group of 1.8 pounds, resulting in a between-group difference of 3.1 pounds [P = .09],” reported Dr. Nicklas. Adjustment for gestational weight gain and breastfeeding had no substantial effect.

When 12-month weight retention versus prepregnancy weight was assessed, the former was halved in participants in the BAB program.

The control group gained a mean of 10.1 pounds, and those in the intervention group gained a mean of 5.3 pounds, equivalent to a difference of 4.8 pounds (P = .04).

A prespecified analysis was conducted of 120 non-Hispanic women. At 12 months, weight retention, compared with prepregnancy weight showed an increase of 9 pounds in the control group versus 1.8 pounds in the intervention group (P = .01).

By comparison, in the small group of Hispanic women only, weight retention at 12 months compared to prepregnancy weight showed a 12.7-pound increase and a 13.3-pound increase in the control and intervention groups respectively, reported Dr. Nicklas.

Addressing the key question of why the BAB program was ineffective in Hispanic women, Dr. Nicklas said, “The literature tells us that low income Hispanic women are twice as likely to experience postpartum weight retention compared to white non-Hispanic women. But we also know that low-income Hispanic women generally engage less with interventions, and there is a higher acceptance of overweight among this ethnic group.”

The researchers hope to follow the women from their trial to determine who progresses to type 2 diabetes.

“Hispanic women are a high-risk population for gestational diabetes and type 2 diabetes, and we plan to identify the best options to help Hispanic women with a history of gestational diabetes prevent type 2 diabetes,” Dr. Nicklas said in an interview.

Dr. Qian also remarked on the differences observed in the weight loss outcomes for non-Hispanic versus Hispanic women, noting that it highlights the importance of studying lifestyle interventions in diverse populations. “Environmental and cultural factors that may differ across different racial or ethnic groups could impact the effectiveness of such interventions.

Dr. Nicklas and Dr. Qian have reported no relevant financial relationships.

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