MDedge Endocrinology

San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.  

Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.

Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.

“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.

Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.

While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.

About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.

Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
 

Screen men with hypogonadism or those taking steroids

“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.

Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.

Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.

But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”

ATOM Study: Significant BMD increases at key sites

The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).

The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.

Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).

Three fractures occurred in those receiving placebo and one with abaloparatide.

For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).

The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.

Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).

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

San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.  

Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.

Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.

“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.

Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.

While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.

About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.

Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
 

Screen men with hypogonadism or those taking steroids

“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.

Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.

Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.

But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”

ATOM Study: Significant BMD increases at key sites

The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).

The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.

Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).

Three fractures occurred in those receiving placebo and one with abaloparatide.

For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).

The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.

Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).

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

San Diego – The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.  

Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.

Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck, compared with placebo in men with osteoporosis, with no significant adverse effects.

“Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population,” presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, said in an interview.

Abaloparatide was approved by the U.S. Food and Drug Administration in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven’t responded to or are intolerant of other osteoporosis therapies.

While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.

About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they’re far less likely to be diagnosed or to be included in osteoporosis treatment trials, Dr. Binkley noted.

Asked to comment, session moderator Thanh D. Hoang, DO, told this news organization, “I think it’s a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women.”
 

Screen men with hypogonadism or those taking steroids

“This new medication is an addition to the very limited number of treatments that we have when patients don’t respond to [initial] medications. To have another anabolic bone-forming medication is very, very good,” said Dr. Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.

Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.

Dr. Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.

But, he added, “I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don’t have normal bone mineral density ... That’s a group of people we’re ignoring still. They’re not getting diagnosed, and they’re not getting treated.”

ATOM Study: Significant BMD increases at key sites

The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2,000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence, compared with placebo, and also significantly greater reductions in nonvertebral fractures, compared with both placebo and teriparatide (Forteo, Eli Lilly).

The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T score ≤ −2.0 if older than 65 years.

Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).

Three fractures occurred in those receiving placebo and one with abaloparatide.

For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs. placebo).

The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs. 5.1%), nasopharyngitis (8.7% vs. 7.6%), dizziness (8.7% vs. 1.3%), and arthralgia (6.7% vs. 1.3%), with abaloparatide versus placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs. 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.

Dr. Binkley has reported receiving consulting fees from Amgen and research support from Radius. Dr. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).

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

According to the latest evidence, the ketogenic diet is emerging as an effective strategy not only to promote weight loss, but also to manage many comorbidities associated with obesity, including COVID-19. This development was revealed during the 8th International Scientific Symposium New Frontiers in Scientific Research, organized by PronoKal Group and held in Barcelona. During this conference, international multidisciplinary experts in the study and management of obesity presented the latest data on the benefits of treatment based on a very-low-calorie ketogenic diet.

“Nutritional ketosis has gained great interest in recent years because it is shown to have beneficial properties for health and promotes healthy aging, increasing longevity,” said Ana Belén Crujeiras, BSc, PhD, principal investigator of the Health Research Institute of Santiago de Compostela-Galician Health Service (IDIS-SERGAS) Group of Epigenomics in Endocrinology and Nutrition and the Biomedical Research Networking Center for Obesity and Nutrition Physiopathology (CIBEROBN). “Furthermore, in the case of obesity, we have more and more evidence that it is an effective treatment, mainly because to achieve this metabolic state (ketosis), routes that require the combustion of fats are activated, and this induces body weight loss.”

The specialist stressed that several strategies are used to induce nutritional ketosis. They are characterized by low carbohydrate consumption (low-carbohydrate and high-fat diet; low-carbohydrate, low-fat diet; and intermittent fasting). But Dr. Crujeiras warned that to use it as a treatment for a disease such as obesity, it must be backed by strong and solid scientific evidence, moving away from the concept of fad diets.

In this sense, since 2010, Dr. Crujeiras’ team has developed several studies focused on analyzing the efficacy and safety of treatment with a very-low-calorie ketogenic diet, the results of which have been published in high-impact journals.

Dr. Crujeiras commented on the main conclusions drawn from these investigations. “Our work has shown that the very-low-calorie ketogenic diet is effective for rapid weight loss and maintenance of lost weight, as well as reducing fat mass, primarily visceral fat mass.

“In this sense, a very interesting result is that despite the strong weight loss it induces, it preserves muscle mass and function and improves resting metabolic rate. These two variables are important, because all therapeutic strategies that exist to lose weight lead to a significant reduction in fat-free mass and also a reduction in energy expenditure at rest. This factor is associated with the risk of regaining lost weight, which is currently the great challenge in the treatment of obesity,” she added.
 

Specific methylation pattern

Dr. Crujeiras indicated that other notable evidence is the favorable impact on an emotional and psychological level. “To determine whether the caloric restriction of this diet and the strong weight loss that it involves were associated with an increased desire to eat, we also carried out an analysis with psychobiological tests. These results led us to conclude that this guideline is accompanied by a reduction of anxiety about food and an improvement in psychobiological parameters, thus increasing the quality of life of these patients.”

The specialist also mentioned that studies currently in progress show that the beneficial effect of this diet could be mediated by epigenetic mechanisms. “In our group, we have identified a specific DNA methylation pattern in people with obesity and we wondered if the very-low-calorie ketogenic diet would be able to reverse that methylome.

“We conducted a study in which we collected blood samples from patients on the very-low-calorie ketogenic diet (600 to 800 kcal/day) drawn before treatment, at peak ketosis, and at the end of treatment. After determining the global pattern of DNA in all patients with obesity targeted with this strategy and through bioinformatic analysis, we were able to obtain a methylation pattern. The results showed that after weight loss on the very-low-calorie ketogenic diet, the methylome that obese people initially had [was] reversed and matched that of normal-weight people.

“Continuing with this bioinformatic analysis more comprehensively, we wanted to see what kind of genes were differentially methylated, especially by the action of the ketosis itself. We found that most of the genes that exhibited differential methylation (in total, 292 identified) belonged to pathways that were involved in the regulation of metabolism, adipose tissue function, CNS function, and also carcinogenesis,” she continued.
 

Immunomodulatory effect

Dr. Crujeiras said that her research group also observed the modulatory role of the very-low-calorie ketogenic diet in the functioning of the immune system, “something that was not seen after similar weight loss induced by bariatric surgery. We analyzed this data in the context of the situation created by COVID-19, taking into account the evidence that people with obesity, compared to those with normal weight, have a higher risk of becoming infected and of having a poor evolution of the infection.”

In this regard, Dr. Crujeiras’ team launched an investigation to study the ACE2 gene methylation pattern, comparing obesity with normal weight and the situation after following a very-low-calorie ketogenic diet or undergoing bariatric surgery. “We observed that the methylation pattern of this gene in obese people was increased, compared to normal-weight people,” she explained, “and this increase was observed mainly in visceral adipose tissue. However, we did not see this in subcutaneous adipose tissue, which is in agreement with the hypothesis that visceral adipose tissue is that mostly associated with obesity-related comorbidities.

“Likewise, the very-low-calorie ketogenic diet was associated with decreased ACE2 methylation, along with increased exposure of this gene. However, after bariatric surgery, no significant changes were observed, so we deduce that we are protecting the patient in some way from inflammation and, therefore, from the potential of serious illness if they become infected.

“In light of these results, we wanted to dig deeper into what was happening with the immune system of obese patients and that inflammation after a very-low-calorie ketogenic diet. We conducted a new study, currently under review in the journal Clinical Nutrition, with the same approach, comparing this diet with a standard hypocaloric balanced diet and bariatric surgery, in which we analyzed a wide battery of cytokines (32). We have observed a differential pattern between the very-low-calorie ketogenic diet and bariatric surgery.

“The results confirm our hypothesis that the very-low-calorie ketogenic diet remodels the inflammatory status of obese patients, and we were also able to verify that the increase in ketone bodies has immunomodulatory properties that were previously demonstrated in preclinical and animal models, which is associated with increased immune function in these patients,” added Dr. Crujeiras.
 

Personalization and weight regain

In regard to the next steps to take in the knowledge and clinical application of the benefits of this dietary strategy, Dr. Crujeiras said that despite the fact that this diet is known to be effective, it is currently prescribed in a standard manner to all patients, “but there is some variability in the response and also a high risk of regaining weight, as is the case with any nutritional intervention strategy, with that ‘regain’ of lost weight being the main challenge in the treatment of obesity. In this sense, the epigenomic and epigenetic markers that we have identified could help us optimize treatment.”

She added that the future lies in establishing an algorithm that encompasses the patient’s exposome data, along with their genetic and epigenetic profile, to properly classify patients and prescribe a personalized precision therapeutic strategy.

Luca Busetto, MD, cochair of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO), also insisted on the challenge posed by the individualized application of the very-low-calorie ketogenic diet, emphasizing that this diet should always be prescribed by a doctor after an appropriate assessment of the patient. “Obesity is not a matter of willpower or motivation, and most people with obesity have struggled their entire lives and failed because their biology tends to cause weight regain. Therefore, we should try to offer them the options that we currently have, including the very-low-calorie ketogenic diet, adapting them as much as possible to the profile of each patient.”

During his speech, Dr. Busetto presented the recent European guidelines for the management of obesity in adults with a very-low-calorie ketogenic diet, endorsed by EASO, and analyzed the main strengths of these recommendations.

Dr. Busetto remarked that three important points clearly justify the use of the very-low-calorie ketogenic diet. The first is the speed with which the initial weight loss occurs. Recent studies have looked at the benefits of a significant loss of excess weight early in a weight-loss diet, and although this is an association rather than a cause, the results strongly suggest that rapid initial weight loss increases the chance of the result being maintained in the long term. This clashes with the traditional recommendation of losing weight little by little as a strategy to achieve long-term results, but it must be taken into account that there are many myths in the treatment of obesity that current evidence is dismantling with new data – and this is one of them.

Secondly, the effect of the very-low-calorie ketogenic diet can be added to other treatments. This has been demonstrated by studies carried out with liraglutide that showed that this dietary strategy optimizes results, compared with patients who had been treated only with this drug. The third point that justifies the use of the very-low-calorie ketogenic diet is the management of obesity comorbidities. Several investigations demonstrate the effectiveness of this diet in this regard, especially in the case of type 2 diabetes. Data suggest that the substantial weight reductions achieved with it also favor the remission of these comorbidities in many patients.
 

EASO ‘approval’

Dr. Busetto pointed out that, based on this evidence, the OMTF proposed the development of standards to be included in the EASO guidelines, since there had been no specific recommendation on the very-low-calorie ketogenic diet.

“The main objective of these European guidelines was to provide data referenced by scientific evidence and to suggest a common protocol for the use of this dietary strategy,” he added.

For this, a very exhaustive meta-analysis was carried out, researching all the publications that compared the very-low-calorie ketogenic diet with other diets. The results showed the superiority of the former method for the reduction of body mass index and weight and fat mass, with no difference in lean (muscle) mass, despite significant weight loss in these patients.

This evidence also demonstrates a reduction and an improvement in metabolic markers, specifically glucose metabolism and lipid metabolism.

“The final conclusions of the study corroborate that the very-low-calorie ketogenic diet can be recommended as an effective and safe tool for people with obesity, especially those with severe obesity or comorbidities (joint disease, preoperative period to bariatric surgery, metabolic and cardiovascular diseases) who need immediate, substantial weight loss. In addition, it can be prescribed to specific groups of patients with obesity after considering potential contraindications and under medical follow-up,” said Dr. Busetto.

In Dr. Busetto’s opinion, it would be convenient to refer to this approach as a method, instead of as a diet, “because, in reality, the state of ketosis is limited in time, and if the ketogenic phase is stopped without a continuity plan, obviously weight is regained. In addition, the method approach may increase adherence by patients.”

Finally, Dr. Busetto emphasized the importance of integrating this type of treatment into a long-term lifestyle strategy (including habits, exercise, and nutritional advice). “We must start from the basis that obesity is a chronic and relapsing disease, whose management should also be chronic and probably maintained throughout life.”

Dr. Crujeiras and Dr. Busetto have disclosed no relevant financial relationships. PronoKal Group has recently become part of Nestlé Health Science.

A version of this article appeared on Medscape.com. It was translated from Medscape Spanish Edition.

According to the latest evidence, the ketogenic diet is emerging as an effective strategy not only to promote weight loss, but also to manage many comorbidities associated with obesity, including COVID-19. This development was revealed during the 8th International Scientific Symposium New Frontiers in Scientific Research, organized by PronoKal Group and held in Barcelona. During this conference, international multidisciplinary experts in the study and management of obesity presented the latest data on the benefits of treatment based on a very-low-calorie ketogenic diet.

“Nutritional ketosis has gained great interest in recent years because it is shown to have beneficial properties for health and promotes healthy aging, increasing longevity,” said Ana Belén Crujeiras, BSc, PhD, principal investigator of the Health Research Institute of Santiago de Compostela-Galician Health Service (IDIS-SERGAS) Group of Epigenomics in Endocrinology and Nutrition and the Biomedical Research Networking Center for Obesity and Nutrition Physiopathology (CIBEROBN). “Furthermore, in the case of obesity, we have more and more evidence that it is an effective treatment, mainly because to achieve this metabolic state (ketosis), routes that require the combustion of fats are activated, and this induces body weight loss.”

The specialist stressed that several strategies are used to induce nutritional ketosis. They are characterized by low carbohydrate consumption (low-carbohydrate and high-fat diet; low-carbohydrate, low-fat diet; and intermittent fasting). But Dr. Crujeiras warned that to use it as a treatment for a disease such as obesity, it must be backed by strong and solid scientific evidence, moving away from the concept of fad diets.

In this sense, since 2010, Dr. Crujeiras’ team has developed several studies focused on analyzing the efficacy and safety of treatment with a very-low-calorie ketogenic diet, the results of which have been published in high-impact journals.

Dr. Crujeiras commented on the main conclusions drawn from these investigations. “Our work has shown that the very-low-calorie ketogenic diet is effective for rapid weight loss and maintenance of lost weight, as well as reducing fat mass, primarily visceral fat mass.

“In this sense, a very interesting result is that despite the strong weight loss it induces, it preserves muscle mass and function and improves resting metabolic rate. These two variables are important, because all therapeutic strategies that exist to lose weight lead to a significant reduction in fat-free mass and also a reduction in energy expenditure at rest. This factor is associated with the risk of regaining lost weight, which is currently the great challenge in the treatment of obesity,” she added.
 

Specific methylation pattern

Dr. Crujeiras indicated that other notable evidence is the favorable impact on an emotional and psychological level. “To determine whether the caloric restriction of this diet and the strong weight loss that it involves were associated with an increased desire to eat, we also carried out an analysis with psychobiological tests. These results led us to conclude that this guideline is accompanied by a reduction of anxiety about food and an improvement in psychobiological parameters, thus increasing the quality of life of these patients.”

The specialist also mentioned that studies currently in progress show that the beneficial effect of this diet could be mediated by epigenetic mechanisms. “In our group, we have identified a specific DNA methylation pattern in people with obesity and we wondered if the very-low-calorie ketogenic diet would be able to reverse that methylome.

“We conducted a study in which we collected blood samples from patients on the very-low-calorie ketogenic diet (600 to 800 kcal/day) drawn before treatment, at peak ketosis, and at the end of treatment. After determining the global pattern of DNA in all patients with obesity targeted with this strategy and through bioinformatic analysis, we were able to obtain a methylation pattern. The results showed that after weight loss on the very-low-calorie ketogenic diet, the methylome that obese people initially had [was] reversed and matched that of normal-weight people.

“Continuing with this bioinformatic analysis more comprehensively, we wanted to see what kind of genes were differentially methylated, especially by the action of the ketosis itself. We found that most of the genes that exhibited differential methylation (in total, 292 identified) belonged to pathways that were involved in the regulation of metabolism, adipose tissue function, CNS function, and also carcinogenesis,” she continued.
 

Immunomodulatory effect

Dr. Crujeiras said that her research group also observed the modulatory role of the very-low-calorie ketogenic diet in the functioning of the immune system, “something that was not seen after similar weight loss induced by bariatric surgery. We analyzed this data in the context of the situation created by COVID-19, taking into account the evidence that people with obesity, compared to those with normal weight, have a higher risk of becoming infected and of having a poor evolution of the infection.”

In this regard, Dr. Crujeiras’ team launched an investigation to study the ACE2 gene methylation pattern, comparing obesity with normal weight and the situation after following a very-low-calorie ketogenic diet or undergoing bariatric surgery. “We observed that the methylation pattern of this gene in obese people was increased, compared to normal-weight people,” she explained, “and this increase was observed mainly in visceral adipose tissue. However, we did not see this in subcutaneous adipose tissue, which is in agreement with the hypothesis that visceral adipose tissue is that mostly associated with obesity-related comorbidities.

“Likewise, the very-low-calorie ketogenic diet was associated with decreased ACE2 methylation, along with increased exposure of this gene. However, after bariatric surgery, no significant changes were observed, so we deduce that we are protecting the patient in some way from inflammation and, therefore, from the potential of serious illness if they become infected.

“In light of these results, we wanted to dig deeper into what was happening with the immune system of obese patients and that inflammation after a very-low-calorie ketogenic diet. We conducted a new study, currently under review in the journal Clinical Nutrition, with the same approach, comparing this diet with a standard hypocaloric balanced diet and bariatric surgery, in which we analyzed a wide battery of cytokines (32). We have observed a differential pattern between the very-low-calorie ketogenic diet and bariatric surgery.

“The results confirm our hypothesis that the very-low-calorie ketogenic diet remodels the inflammatory status of obese patients, and we were also able to verify that the increase in ketone bodies has immunomodulatory properties that were previously demonstrated in preclinical and animal models, which is associated with increased immune function in these patients,” added Dr. Crujeiras.
 

Personalization and weight regain

In regard to the next steps to take in the knowledge and clinical application of the benefits of this dietary strategy, Dr. Crujeiras said that despite the fact that this diet is known to be effective, it is currently prescribed in a standard manner to all patients, “but there is some variability in the response and also a high risk of regaining weight, as is the case with any nutritional intervention strategy, with that ‘regain’ of lost weight being the main challenge in the treatment of obesity. In this sense, the epigenomic and epigenetic markers that we have identified could help us optimize treatment.”

She added that the future lies in establishing an algorithm that encompasses the patient’s exposome data, along with their genetic and epigenetic profile, to properly classify patients and prescribe a personalized precision therapeutic strategy.

Luca Busetto, MD, cochair of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO), also insisted on the challenge posed by the individualized application of the very-low-calorie ketogenic diet, emphasizing that this diet should always be prescribed by a doctor after an appropriate assessment of the patient. “Obesity is not a matter of willpower or motivation, and most people with obesity have struggled their entire lives and failed because their biology tends to cause weight regain. Therefore, we should try to offer them the options that we currently have, including the very-low-calorie ketogenic diet, adapting them as much as possible to the profile of each patient.”

During his speech, Dr. Busetto presented the recent European guidelines for the management of obesity in adults with a very-low-calorie ketogenic diet, endorsed by EASO, and analyzed the main strengths of these recommendations.

Dr. Busetto remarked that three important points clearly justify the use of the very-low-calorie ketogenic diet. The first is the speed with which the initial weight loss occurs. Recent studies have looked at the benefits of a significant loss of excess weight early in a weight-loss diet, and although this is an association rather than a cause, the results strongly suggest that rapid initial weight loss increases the chance of the result being maintained in the long term. This clashes with the traditional recommendation of losing weight little by little as a strategy to achieve long-term results, but it must be taken into account that there are many myths in the treatment of obesity that current evidence is dismantling with new data – and this is one of them.

Secondly, the effect of the very-low-calorie ketogenic diet can be added to other treatments. This has been demonstrated by studies carried out with liraglutide that showed that this dietary strategy optimizes results, compared with patients who had been treated only with this drug. The third point that justifies the use of the very-low-calorie ketogenic diet is the management of obesity comorbidities. Several investigations demonstrate the effectiveness of this diet in this regard, especially in the case of type 2 diabetes. Data suggest that the substantial weight reductions achieved with it also favor the remission of these comorbidities in many patients.
 

EASO ‘approval’

Dr. Busetto pointed out that, based on this evidence, the OMTF proposed the development of standards to be included in the EASO guidelines, since there had been no specific recommendation on the very-low-calorie ketogenic diet.

“The main objective of these European guidelines was to provide data referenced by scientific evidence and to suggest a common protocol for the use of this dietary strategy,” he added.

For this, a very exhaustive meta-analysis was carried out, researching all the publications that compared the very-low-calorie ketogenic diet with other diets. The results showed the superiority of the former method for the reduction of body mass index and weight and fat mass, with no difference in lean (muscle) mass, despite significant weight loss in these patients.

This evidence also demonstrates a reduction and an improvement in metabolic markers, specifically glucose metabolism and lipid metabolism.

“The final conclusions of the study corroborate that the very-low-calorie ketogenic diet can be recommended as an effective and safe tool for people with obesity, especially those with severe obesity or comorbidities (joint disease, preoperative period to bariatric surgery, metabolic and cardiovascular diseases) who need immediate, substantial weight loss. In addition, it can be prescribed to specific groups of patients with obesity after considering potential contraindications and under medical follow-up,” said Dr. Busetto.

In Dr. Busetto’s opinion, it would be convenient to refer to this approach as a method, instead of as a diet, “because, in reality, the state of ketosis is limited in time, and if the ketogenic phase is stopped without a continuity plan, obviously weight is regained. In addition, the method approach may increase adherence by patients.”

Finally, Dr. Busetto emphasized the importance of integrating this type of treatment into a long-term lifestyle strategy (including habits, exercise, and nutritional advice). “We must start from the basis that obesity is a chronic and relapsing disease, whose management should also be chronic and probably maintained throughout life.”

Dr. Crujeiras and Dr. Busetto have disclosed no relevant financial relationships. PronoKal Group has recently become part of Nestlé Health Science.

A version of this article appeared on Medscape.com. It was translated from Medscape Spanish Edition.

According to the latest evidence, the ketogenic diet is emerging as an effective strategy not only to promote weight loss, but also to manage many comorbidities associated with obesity, including COVID-19. This development was revealed during the 8th International Scientific Symposium New Frontiers in Scientific Research, organized by PronoKal Group and held in Barcelona. During this conference, international multidisciplinary experts in the study and management of obesity presented the latest data on the benefits of treatment based on a very-low-calorie ketogenic diet.

“Nutritional ketosis has gained great interest in recent years because it is shown to have beneficial properties for health and promotes healthy aging, increasing longevity,” said Ana Belén Crujeiras, BSc, PhD, principal investigator of the Health Research Institute of Santiago de Compostela-Galician Health Service (IDIS-SERGAS) Group of Epigenomics in Endocrinology and Nutrition and the Biomedical Research Networking Center for Obesity and Nutrition Physiopathology (CIBEROBN). “Furthermore, in the case of obesity, we have more and more evidence that it is an effective treatment, mainly because to achieve this metabolic state (ketosis), routes that require the combustion of fats are activated, and this induces body weight loss.”

The specialist stressed that several strategies are used to induce nutritional ketosis. They are characterized by low carbohydrate consumption (low-carbohydrate and high-fat diet; low-carbohydrate, low-fat diet; and intermittent fasting). But Dr. Crujeiras warned that to use it as a treatment for a disease such as obesity, it must be backed by strong and solid scientific evidence, moving away from the concept of fad diets.

In this sense, since 2010, Dr. Crujeiras’ team has developed several studies focused on analyzing the efficacy and safety of treatment with a very-low-calorie ketogenic diet, the results of which have been published in high-impact journals.

Dr. Crujeiras commented on the main conclusions drawn from these investigations. “Our work has shown that the very-low-calorie ketogenic diet is effective for rapid weight loss and maintenance of lost weight, as well as reducing fat mass, primarily visceral fat mass.

“In this sense, a very interesting result is that despite the strong weight loss it induces, it preserves muscle mass and function and improves resting metabolic rate. These two variables are important, because all therapeutic strategies that exist to lose weight lead to a significant reduction in fat-free mass and also a reduction in energy expenditure at rest. This factor is associated with the risk of regaining lost weight, which is currently the great challenge in the treatment of obesity,” she added.
 

Specific methylation pattern

Dr. Crujeiras indicated that other notable evidence is the favorable impact on an emotional and psychological level. “To determine whether the caloric restriction of this diet and the strong weight loss that it involves were associated with an increased desire to eat, we also carried out an analysis with psychobiological tests. These results led us to conclude that this guideline is accompanied by a reduction of anxiety about food and an improvement in psychobiological parameters, thus increasing the quality of life of these patients.”

The specialist also mentioned that studies currently in progress show that the beneficial effect of this diet could be mediated by epigenetic mechanisms. “In our group, we have identified a specific DNA methylation pattern in people with obesity and we wondered if the very-low-calorie ketogenic diet would be able to reverse that methylome.

“We conducted a study in which we collected blood samples from patients on the very-low-calorie ketogenic diet (600 to 800 kcal/day) drawn before treatment, at peak ketosis, and at the end of treatment. After determining the global pattern of DNA in all patients with obesity targeted with this strategy and through bioinformatic analysis, we were able to obtain a methylation pattern. The results showed that after weight loss on the very-low-calorie ketogenic diet, the methylome that obese people initially had [was] reversed and matched that of normal-weight people.

“Continuing with this bioinformatic analysis more comprehensively, we wanted to see what kind of genes were differentially methylated, especially by the action of the ketosis itself. We found that most of the genes that exhibited differential methylation (in total, 292 identified) belonged to pathways that were involved in the regulation of metabolism, adipose tissue function, CNS function, and also carcinogenesis,” she continued.
 

Immunomodulatory effect

Dr. Crujeiras said that her research group also observed the modulatory role of the very-low-calorie ketogenic diet in the functioning of the immune system, “something that was not seen after similar weight loss induced by bariatric surgery. We analyzed this data in the context of the situation created by COVID-19, taking into account the evidence that people with obesity, compared to those with normal weight, have a higher risk of becoming infected and of having a poor evolution of the infection.”

In this regard, Dr. Crujeiras’ team launched an investigation to study the ACE2 gene methylation pattern, comparing obesity with normal weight and the situation after following a very-low-calorie ketogenic diet or undergoing bariatric surgery. “We observed that the methylation pattern of this gene in obese people was increased, compared to normal-weight people,” she explained, “and this increase was observed mainly in visceral adipose tissue. However, we did not see this in subcutaneous adipose tissue, which is in agreement with the hypothesis that visceral adipose tissue is that mostly associated with obesity-related comorbidities.

“Likewise, the very-low-calorie ketogenic diet was associated with decreased ACE2 methylation, along with increased exposure of this gene. However, after bariatric surgery, no significant changes were observed, so we deduce that we are protecting the patient in some way from inflammation and, therefore, from the potential of serious illness if they become infected.

“In light of these results, we wanted to dig deeper into what was happening with the immune system of obese patients and that inflammation after a very-low-calorie ketogenic diet. We conducted a new study, currently under review in the journal Clinical Nutrition, with the same approach, comparing this diet with a standard hypocaloric balanced diet and bariatric surgery, in which we analyzed a wide battery of cytokines (32). We have observed a differential pattern between the very-low-calorie ketogenic diet and bariatric surgery.

“The results confirm our hypothesis that the very-low-calorie ketogenic diet remodels the inflammatory status of obese patients, and we were also able to verify that the increase in ketone bodies has immunomodulatory properties that were previously demonstrated in preclinical and animal models, which is associated with increased immune function in these patients,” added Dr. Crujeiras.
 

Personalization and weight regain

In regard to the next steps to take in the knowledge and clinical application of the benefits of this dietary strategy, Dr. Crujeiras said that despite the fact that this diet is known to be effective, it is currently prescribed in a standard manner to all patients, “but there is some variability in the response and also a high risk of regaining weight, as is the case with any nutritional intervention strategy, with that ‘regain’ of lost weight being the main challenge in the treatment of obesity. In this sense, the epigenomic and epigenetic markers that we have identified could help us optimize treatment.”

She added that the future lies in establishing an algorithm that encompasses the patient’s exposome data, along with their genetic and epigenetic profile, to properly classify patients and prescribe a personalized precision therapeutic strategy.

Luca Busetto, MD, cochair of the Obesity Management Task Force (OMTF) of the European Association for the Study of Obesity (EASO), also insisted on the challenge posed by the individualized application of the very-low-calorie ketogenic diet, emphasizing that this diet should always be prescribed by a doctor after an appropriate assessment of the patient. “Obesity is not a matter of willpower or motivation, and most people with obesity have struggled their entire lives and failed because their biology tends to cause weight regain. Therefore, we should try to offer them the options that we currently have, including the very-low-calorie ketogenic diet, adapting them as much as possible to the profile of each patient.”

During his speech, Dr. Busetto presented the recent European guidelines for the management of obesity in adults with a very-low-calorie ketogenic diet, endorsed by EASO, and analyzed the main strengths of these recommendations.

Dr. Busetto remarked that three important points clearly justify the use of the very-low-calorie ketogenic diet. The first is the speed with which the initial weight loss occurs. Recent studies have looked at the benefits of a significant loss of excess weight early in a weight-loss diet, and although this is an association rather than a cause, the results strongly suggest that rapid initial weight loss increases the chance of the result being maintained in the long term. This clashes with the traditional recommendation of losing weight little by little as a strategy to achieve long-term results, but it must be taken into account that there are many myths in the treatment of obesity that current evidence is dismantling with new data – and this is one of them.

Secondly, the effect of the very-low-calorie ketogenic diet can be added to other treatments. This has been demonstrated by studies carried out with liraglutide that showed that this dietary strategy optimizes results, compared with patients who had been treated only with this drug. The third point that justifies the use of the very-low-calorie ketogenic diet is the management of obesity comorbidities. Several investigations demonstrate the effectiveness of this diet in this regard, especially in the case of type 2 diabetes. Data suggest that the substantial weight reductions achieved with it also favor the remission of these comorbidities in many patients.
 

EASO ‘approval’

Dr. Busetto pointed out that, based on this evidence, the OMTF proposed the development of standards to be included in the EASO guidelines, since there had been no specific recommendation on the very-low-calorie ketogenic diet.

“The main objective of these European guidelines was to provide data referenced by scientific evidence and to suggest a common protocol for the use of this dietary strategy,” he added.

For this, a very exhaustive meta-analysis was carried out, researching all the publications that compared the very-low-calorie ketogenic diet with other diets. The results showed the superiority of the former method for the reduction of body mass index and weight and fat mass, with no difference in lean (muscle) mass, despite significant weight loss in these patients.

This evidence also demonstrates a reduction and an improvement in metabolic markers, specifically glucose metabolism and lipid metabolism.

“The final conclusions of the study corroborate that the very-low-calorie ketogenic diet can be recommended as an effective and safe tool for people with obesity, especially those with severe obesity or comorbidities (joint disease, preoperative period to bariatric surgery, metabolic and cardiovascular diseases) who need immediate, substantial weight loss. In addition, it can be prescribed to specific groups of patients with obesity after considering potential contraindications and under medical follow-up,” said Dr. Busetto.

In Dr. Busetto’s opinion, it would be convenient to refer to this approach as a method, instead of as a diet, “because, in reality, the state of ketosis is limited in time, and if the ketogenic phase is stopped without a continuity plan, obviously weight is regained. In addition, the method approach may increase adherence by patients.”

Finally, Dr. Busetto emphasized the importance of integrating this type of treatment into a long-term lifestyle strategy (including habits, exercise, and nutritional advice). “We must start from the basis that obesity is a chronic and relapsing disease, whose management should also be chronic and probably maintained throughout life.”

Dr. Crujeiras and Dr. Busetto have disclosed no relevant financial relationships. PronoKal Group has recently become part of Nestlé Health Science.

A version of this article appeared on Medscape.com. It was translated from Medscape Spanish Edition.

Early in the COVID-19 pandemic, Trisha Pasricha, MD, a gastroenterologist and research fellow at Massachusetts General Hospital in Boston, was talking to a patient who had been hospitalized for a peptic ulcer.

Like other physicians in her institution, Dr. Pasricha was wearing scrubs instead of a white coat, out of concern that the white coat might be more prone to accumulating or transmitting COVID-19 pathogens. Her badge identified her as a physician, and she introduced herself clearly as “Dr. Pasricha.”

The patient “required an emergent procedure, which I discussed with him,” Dr. Pasricha told this news organization. “I went over what the procedure entailed, the risks and benefits, and the need for informed consent. The patient nodded and seemed to understand, but at the end of the discussion he said: ‘That all sounds fine, but I need to speak to the doctor first.’ ”

Dr. Pasricha was taken aback. She wondered: “Who did he think I was the whole time that I was reviewing medical concerns, explaining medical concepts, and describing a procedure in a way that a physician would describe it?”

She realized the reason he didn’t correctly identify her was that, clad only in scrubs, she was less easily recognizable as a physician. And while this type of misidentification happened to physicians of both genders wearing scrubs and no white coat, it was more common for female than for male physicians to be misidentified as technicians, nurses, physician assistants, or other health care professionals, according to Dr. Pasricha.

Dr. Pasricha said she has been the recipient of this “implicit bias” not only from patients but also from members of the health care team, and added that other female colleagues have told her that they’ve had similar experiences, especially when they’re not wearing a white coat.
 

Changing times, changing trends

When COVID-19 began to spread, “there was an initial concern that COVID-19 was passed through surfaces, and concerns about whether white coats could carry viral particles,” according to Jordan Steinberg, MD, PhD, surgical director of the craniofacial program at Nicklaus Children’s Pediatric Specialists/Nicklaus Children’s Health System, Miami. “Hospitals didn’t want to launder the white coats as frequently as scrubs, due to cost concerns. There was also a concern raised that a necktie might dangle in patients’ faces, coming in closer contact with pathogens, so more physicians were wearing scrubs.”

Yet even before the pandemic, physician attire in hospital and outpatient settings had started to change. Dr. Steinberg, who is also a clinical associate professor at Florida International University, Miami, told this news organization that, in his previous appointment at Johns Hopkins University, Baltimore, he and his colleagues “had noticed in our institution, as well as other facilities, an increasing trend that moved from white coats worn over professional attire toward more casual dress among medical staff – increased wearing of casual fleece or softshell jackets with the institutional logo.”

This was especially true with trainees and the “younger generation,” who were preferring “what I would almost call ‘warm-up clothes,’ gym clothes, and less shirt-tie-white-coat attire for men or white-coats-and-business attire for women.” Dr. Steinberg thinks that some physicians prefer the fleece with the institutional logo “because it’s like wearing your favorite sports team jersey. It gives a sense of belonging.”

Todd Shaffer, MD, MBA, a family physician at University Physicians Associates, Truman Medical Centers and the Lakewood Medical Pavilion, Kansas City, Mo., has been at his institution for 30 years and has seen a similar trend. “At one point, things were very formal,” he told this news organization. But attire was already becoming less formal before the pandemic, and new changes took place during the pandemic, as physicians began wearing scrubs instead of white coats because of fears of viral contamination.

Now, there is less concern about potential viral contamination with the white coat. Yet many physicians continue to wear scrubs – especially those who interact with patients with COVID – and it has become more acceptable to do so, or to wear personal protective equipment (PPE) over ordinary clothing, but it is less common in routine clinical practice, said Dr. Shaffer, a member of the board of directors of the American Academy of Family Physicians.

“The world has changed since COVID. People feel more comfortable dressing more casually during professional Zoom calls, when they have the convenience of working from home,” said Dr. Shaffer, who is also a professor of family medicine at University of Missouri–Kansas City.

Dr. Shaffer himself hasn’t worn a white coat for years. “I’m more likely to wear medium casual pants. I’ve bought some nicer shirts, so I still look professional and upbeat. I don’t always tuck in my shirt, and I don’t dress as formally.” He wears PPE and a mask and/or face shield when treating patients with COVID-19. And he wears a white coat “when someone wants a photograph taken with the doctors – with the stethoscope draped around my neck.”
 

Traditional symbol of medicine

Because of the changing mores, Dr. Steinberg and colleagues at Johns Hopkins wondered if there might still be a role for professional attire and white coats and what patients prefer. To investigate the question, they surveyed 487 U.S. adults in the spring of 2020.

Respondents were asked where and how frequently they see health care professionals wearing white coats, scrubs, and fleece or softshell jackets. They were also shown photographs depicting models wearing various types of attire commonly seen in health care settings and were asked to rank the “health care provider’s” level of experience, professionalism, and friendliness.

The majority of participants said they had seen health care practitioners in white coats “most of the time,” in scrubs “sometimes,” and in fleece or softshell jackets “rarely.” Models in white coats were regarded by respondents as more experienced and professional, although those in softshell jackets were perceived as friendlier.

There were age as well as regional differences in the responses, Dr. Steinberg said. Older respondents were significantly more likely than their younger counterparts to perceive a model wearing a white coat over business attire as being more experienced, and – in all regions of the United States except the West coast – respondents gave lower professionalism scores to providers wearing fleece jackets with scrubs underneath.

Respondents tended to prefer surgeons wearing a white coat with scrubs underneath, while a white coat over business attire was the preferred dress code for family physicians and dermatologists.

“People tended to respond as if there was a more professional element in the white coat. The age-old symbol of the white coat still marked something important,” Dr. Steinberg said. “Our data suggest that the white coat isn’t ready to die just yet. People still see an air of authority and a traditional symbol of medicine. Nevertheless, I do think it will become less common than it used to be, especially in certain regions of the country.”
 

Organic, subtle changes

Christopher Petrilli, MD, assistant professor at New York University, conducted research in 2018 regarding physician attire by surveying over 4,000 patients in 10 U.S. academic hospitals. His team found that most patients continued to prefer physicians to wear formal attire under a white coat, especially older respondents.

Dr. Petrilli and colleagues have been studying the issue of physician attire since 2015. “The big issue when we did our initial study – which might not be accurate anymore – is that few hospitals actually had a uniform dress code,” said Dr. Petrilli, the medical director of clinical documentation improvement and the clinical lead of value-based medicine at NYU Langone Hospitals. “When we looked at ‘honor roll hospitals’ during our study, we cold-called these hospitals and also looked online for their dress code policies. Except for the Mayo Clinic, hospitals that had dress code policies were more generic.”

For example, the American Medical Association guidance merely states that attire should be “clean, unsoiled, and appropriate to the setting of care” and recommends weighing research findings regarding textile transmission of health care–associated infections when individual institutions determine their dress code policies. The AMA’s last policy discussion took place in 2015 and its guidance has not changed since the pandemic.

Regardless of what institutions and patients prefer, some research suggests that many physicians would prefer to stay with wearing scrubs rather than reverting to the white coat. One study of 151 hospitalists, conducted in Ireland, found that three-quarters wanted scrubs to remain standard attire, despite the fact that close to half had experienced changes in patients› perception in the absence of their white coat and “professional attire.”

Jennifer Workman, MD, assistant professor of pediatrics, division of pediatric critical care, University of Utah, Salt Lake City, said in an interview that, as the pandemic has “waxed and waned, some trends have reverted to what they were prepandemic, but other physicians have stayed with wearing scrubs.”

Much depends on practice setting, said Dr. Workman, who is also the medical director of pediatric sepsis at Intermountain Care. In pediatrics, for example, many physicians prefer not to wear white coats when they are interacting with young children or adolescents.

Like Dr. Shaffer, Dr. Workman has seen changes in physicians’ attire during video meetings, where they often dress more casually, perhaps wearing sweatshirts. And in the hospital, more are continuing to wear scrubs. “But I don’t see it as people trying to consciously experiment or push boundaries,” she said. “I see it as a more organic, subtle shift.”

Dr. Petrilli thinks that, at this juncture, it’s “pretty heterogeneous as to who is going to return to formal attire and a white coat and who won’t.” Further research needs to be done into currently evolving trends. “We need a more thorough survey looking at changes. We need to ask [physician respondents]: ‘What is your current attire, and how has it changed?’ ”
 

Navigating the gender divide

In their study, Dr. Steinberg and colleagues found that respondents perceived a male model wearing business attire underneath any type of outerwear (white coat or fleece) to be significantly more professional than a female model wearing the same attire. Respondents also perceived males wearing scrubs to be more professional than females wearing scrubs.

Male models in white coats over business attire were also more likely to be identified as physicians, compared with female models in the same attire. Females were also more likely to be misidentified as nonphysician health care professionals.

Shikha Jain, MD, assistant professor of medicine at the University of Illinois Cancer Center in Chicago, said that Dr. Steinberg’s study confirmed experiences that she and other female physicians have had. Wearing a white coat makes it more likely that a patient will identify you as a physician, but women are less likely to be identified as physicians, regardless of what they wear.

“I think that individuals of color and especially people with intersectional identities – such as women of color – are even more frequently targeted and stereotyped. Numerous studies have shown that a person of color is less likely to be seen as an authority figure, and studies have shown that physicians of color are less likely to be identified as ‘physicians,’ compared to a Caucasian individual,” she said.

Does that mean that female physicians should revert back to prepandemic white coats rather than scrubs or more casual attire? Not necessarily, according to Dr. Jain.

“The typical dress code guidance is that physicians should dress ‘professionally,’ but what that means is a question that needs to be addressed,” Dr. Jain said. “Medicine has evolved from the days of house calls, in which one’s patient population is a very small, intimate group of people in the physician’s community. Yet now, we’ve given rebirth to the ‘house call’ when we do telemedicine with a patient in his or her home. And in the old days, doctors often had offices their homes and now, with telemedicine, patients often see the interior of their physician’s home.” As the delivery of medicine evolves, concepts of “professionalism” – what is defined as “casual” and what is defined as “formal” – is also evolving.

The more important issue, according to Dr. Jain, is to “continue the conversation” about the discrepancies between how men and women are treated in medicine. Attire is one arena in which this issue plays out, and it’s a “bigger picture” that goes beyond the white coat.

Dr. Jain has been “told by patients that a particular outfit doesn’t make me look like a doctor or that scrubs make me look younger. I don’t think my male colleagues have been subjected to these types of remarks, but my female colleagues have heard them as well.”

Even fellow health care providers have commented on Dr. Jain’s clothing. She was presenting at a major medical conference via video and was wearing a similar outfit to the one she wore for her headshot. “Thirty seconds before beginning my talk, one of the male physicians said: ‘Are you wearing the same outfit you wore for your headshot?’ I can’t imagine a man commenting that another man was wearing the same jacket or tie that he wore in the photograph. I found it odd that this was something that someone felt the need to comment on right before I was about to address a large group of people in a professional capacity.”

Addressing these systemic issues “needs to be done and amplified not only by women but also by men in medicine,” said Dr. Jain, founder and director of  Women in Medicine, an organization consisting of women physicians whose goal is to “find and implement solutions to gender inequity.”

Dr. Jain said the organization offers an Inclusive Leadership Development Lab – a course specifically for men in health care leadership positions to learn how to be more equitable, inclusive leaders.
 

A personal decision

Dr. Pasricha hopes she “handled the patient’s misidentification graciously.” She explained to him that she would be the physician conducting the procedure. The patient was initially “a little embarrassed” that he had misidentified her, but she put him at ease and “we moved forward quickly.”

At this point, although some of her colleagues have continued to wear scrubs or have returned to wearing fleeces with hospital logos, Dr. Pasricha prefers to wear a white coat in both inpatient and outpatient settings because it reduces the likelihood of misidentification.

And white coats can be more convenient – for example, Dr. Jain likes the fact that the white coat has pockets where she can put her stethoscope and other items, while some of her professional clothes don’t always have pockets.

Dr. Jain noted that there are some institutions where everyone seems to wear white coats, not only the physician – “from the chaplain to the phlebotomist to the social worker.” In those settings, the white coat no longer distinguishes physicians from nonphysicians, and so wearing a white coat may not confer additional credibility as a physician.

Nevertheless, “if you want to wear a white coat, if you feel it gives you that added level of authority, if you feel it tells people more clearly that you’re a physician, by all means go ahead and do so,” she said. “There’s no ‘one-size-fits-all’ strategy or solution. What’s more important than your clothing is your professionalism.”

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

Early in the COVID-19 pandemic, Trisha Pasricha, MD, a gastroenterologist and research fellow at Massachusetts General Hospital in Boston, was talking to a patient who had been hospitalized for a peptic ulcer.

Like other physicians in her institution, Dr. Pasricha was wearing scrubs instead of a white coat, out of concern that the white coat might be more prone to accumulating or transmitting COVID-19 pathogens. Her badge identified her as a physician, and she introduced herself clearly as “Dr. Pasricha.”

The patient “required an emergent procedure, which I discussed with him,” Dr. Pasricha told this news organization. “I went over what the procedure entailed, the risks and benefits, and the need for informed consent. The patient nodded and seemed to understand, but at the end of the discussion he said: ‘That all sounds fine, but I need to speak to the doctor first.’ ”

Dr. Pasricha was taken aback. She wondered: “Who did he think I was the whole time that I was reviewing medical concerns, explaining medical concepts, and describing a procedure in a way that a physician would describe it?”

She realized the reason he didn’t correctly identify her was that, clad only in scrubs, she was less easily recognizable as a physician. And while this type of misidentification happened to physicians of both genders wearing scrubs and no white coat, it was more common for female than for male physicians to be misidentified as technicians, nurses, physician assistants, or other health care professionals, according to Dr. Pasricha.

Dr. Pasricha said she has been the recipient of this “implicit bias” not only from patients but also from members of the health care team, and added that other female colleagues have told her that they’ve had similar experiences, especially when they’re not wearing a white coat.
 

Changing times, changing trends

When COVID-19 began to spread, “there was an initial concern that COVID-19 was passed through surfaces, and concerns about whether white coats could carry viral particles,” according to Jordan Steinberg, MD, PhD, surgical director of the craniofacial program at Nicklaus Children’s Pediatric Specialists/Nicklaus Children’s Health System, Miami. “Hospitals didn’t want to launder the white coats as frequently as scrubs, due to cost concerns. There was also a concern raised that a necktie might dangle in patients’ faces, coming in closer contact with pathogens, so more physicians were wearing scrubs.”

Yet even before the pandemic, physician attire in hospital and outpatient settings had started to change. Dr. Steinberg, who is also a clinical associate professor at Florida International University, Miami, told this news organization that, in his previous appointment at Johns Hopkins University, Baltimore, he and his colleagues “had noticed in our institution, as well as other facilities, an increasing trend that moved from white coats worn over professional attire toward more casual dress among medical staff – increased wearing of casual fleece or softshell jackets with the institutional logo.”

This was especially true with trainees and the “younger generation,” who were preferring “what I would almost call ‘warm-up clothes,’ gym clothes, and less shirt-tie-white-coat attire for men or white-coats-and-business attire for women.” Dr. Steinberg thinks that some physicians prefer the fleece with the institutional logo “because it’s like wearing your favorite sports team jersey. It gives a sense of belonging.”

Todd Shaffer, MD, MBA, a family physician at University Physicians Associates, Truman Medical Centers and the Lakewood Medical Pavilion, Kansas City, Mo., has been at his institution for 30 years and has seen a similar trend. “At one point, things were very formal,” he told this news organization. But attire was already becoming less formal before the pandemic, and new changes took place during the pandemic, as physicians began wearing scrubs instead of white coats because of fears of viral contamination.

Now, there is less concern about potential viral contamination with the white coat. Yet many physicians continue to wear scrubs – especially those who interact with patients with COVID – and it has become more acceptable to do so, or to wear personal protective equipment (PPE) over ordinary clothing, but it is less common in routine clinical practice, said Dr. Shaffer, a member of the board of directors of the American Academy of Family Physicians.

“The world has changed since COVID. People feel more comfortable dressing more casually during professional Zoom calls, when they have the convenience of working from home,” said Dr. Shaffer, who is also a professor of family medicine at University of Missouri–Kansas City.

Dr. Shaffer himself hasn’t worn a white coat for years. “I’m more likely to wear medium casual pants. I’ve bought some nicer shirts, so I still look professional and upbeat. I don’t always tuck in my shirt, and I don’t dress as formally.” He wears PPE and a mask and/or face shield when treating patients with COVID-19. And he wears a white coat “when someone wants a photograph taken with the doctors – with the stethoscope draped around my neck.”
 

Traditional symbol of medicine

Because of the changing mores, Dr. Steinberg and colleagues at Johns Hopkins wondered if there might still be a role for professional attire and white coats and what patients prefer. To investigate the question, they surveyed 487 U.S. adults in the spring of 2020.

Respondents were asked where and how frequently they see health care professionals wearing white coats, scrubs, and fleece or softshell jackets. They were also shown photographs depicting models wearing various types of attire commonly seen in health care settings and were asked to rank the “health care provider’s” level of experience, professionalism, and friendliness.

The majority of participants said they had seen health care practitioners in white coats “most of the time,” in scrubs “sometimes,” and in fleece or softshell jackets “rarely.” Models in white coats were regarded by respondents as more experienced and professional, although those in softshell jackets were perceived as friendlier.

There were age as well as regional differences in the responses, Dr. Steinberg said. Older respondents were significantly more likely than their younger counterparts to perceive a model wearing a white coat over business attire as being more experienced, and – in all regions of the United States except the West coast – respondents gave lower professionalism scores to providers wearing fleece jackets with scrubs underneath.

Respondents tended to prefer surgeons wearing a white coat with scrubs underneath, while a white coat over business attire was the preferred dress code for family physicians and dermatologists.

“People tended to respond as if there was a more professional element in the white coat. The age-old symbol of the white coat still marked something important,” Dr. Steinberg said. “Our data suggest that the white coat isn’t ready to die just yet. People still see an air of authority and a traditional symbol of medicine. Nevertheless, I do think it will become less common than it used to be, especially in certain regions of the country.”
 

Organic, subtle changes

Christopher Petrilli, MD, assistant professor at New York University, conducted research in 2018 regarding physician attire by surveying over 4,000 patients in 10 U.S. academic hospitals. His team found that most patients continued to prefer physicians to wear formal attire under a white coat, especially older respondents.

Dr. Petrilli and colleagues have been studying the issue of physician attire since 2015. “The big issue when we did our initial study – which might not be accurate anymore – is that few hospitals actually had a uniform dress code,” said Dr. Petrilli, the medical director of clinical documentation improvement and the clinical lead of value-based medicine at NYU Langone Hospitals. “When we looked at ‘honor roll hospitals’ during our study, we cold-called these hospitals and also looked online for their dress code policies. Except for the Mayo Clinic, hospitals that had dress code policies were more generic.”

For example, the American Medical Association guidance merely states that attire should be “clean, unsoiled, and appropriate to the setting of care” and recommends weighing research findings regarding textile transmission of health care–associated infections when individual institutions determine their dress code policies. The AMA’s last policy discussion took place in 2015 and its guidance has not changed since the pandemic.

Regardless of what institutions and patients prefer, some research suggests that many physicians would prefer to stay with wearing scrubs rather than reverting to the white coat. One study of 151 hospitalists, conducted in Ireland, found that three-quarters wanted scrubs to remain standard attire, despite the fact that close to half had experienced changes in patients› perception in the absence of their white coat and “professional attire.”

Jennifer Workman, MD, assistant professor of pediatrics, division of pediatric critical care, University of Utah, Salt Lake City, said in an interview that, as the pandemic has “waxed and waned, some trends have reverted to what they were prepandemic, but other physicians have stayed with wearing scrubs.”

Much depends on practice setting, said Dr. Workman, who is also the medical director of pediatric sepsis at Intermountain Care. In pediatrics, for example, many physicians prefer not to wear white coats when they are interacting with young children or adolescents.

Like Dr. Shaffer, Dr. Workman has seen changes in physicians’ attire during video meetings, where they often dress more casually, perhaps wearing sweatshirts. And in the hospital, more are continuing to wear scrubs. “But I don’t see it as people trying to consciously experiment or push boundaries,” she said. “I see it as a more organic, subtle shift.”

Dr. Petrilli thinks that, at this juncture, it’s “pretty heterogeneous as to who is going to return to formal attire and a white coat and who won’t.” Further research needs to be done into currently evolving trends. “We need a more thorough survey looking at changes. We need to ask [physician respondents]: ‘What is your current attire, and how has it changed?’ ”
 

Navigating the gender divide

In their study, Dr. Steinberg and colleagues found that respondents perceived a male model wearing business attire underneath any type of outerwear (white coat or fleece) to be significantly more professional than a female model wearing the same attire. Respondents also perceived males wearing scrubs to be more professional than females wearing scrubs.

Male models in white coats over business attire were also more likely to be identified as physicians, compared with female models in the same attire. Females were also more likely to be misidentified as nonphysician health care professionals.

Shikha Jain, MD, assistant professor of medicine at the University of Illinois Cancer Center in Chicago, said that Dr. Steinberg’s study confirmed experiences that she and other female physicians have had. Wearing a white coat makes it more likely that a patient will identify you as a physician, but women are less likely to be identified as physicians, regardless of what they wear.

“I think that individuals of color and especially people with intersectional identities – such as women of color – are even more frequently targeted and stereotyped. Numerous studies have shown that a person of color is less likely to be seen as an authority figure, and studies have shown that physicians of color are less likely to be identified as ‘physicians,’ compared to a Caucasian individual,” she said.

Does that mean that female physicians should revert back to prepandemic white coats rather than scrubs or more casual attire? Not necessarily, according to Dr. Jain.

“The typical dress code guidance is that physicians should dress ‘professionally,’ but what that means is a question that needs to be addressed,” Dr. Jain said. “Medicine has evolved from the days of house calls, in which one’s patient population is a very small, intimate group of people in the physician’s community. Yet now, we’ve given rebirth to the ‘house call’ when we do telemedicine with a patient in his or her home. And in the old days, doctors often had offices their homes and now, with telemedicine, patients often see the interior of their physician’s home.” As the delivery of medicine evolves, concepts of “professionalism” – what is defined as “casual” and what is defined as “formal” – is also evolving.

The more important issue, according to Dr. Jain, is to “continue the conversation” about the discrepancies between how men and women are treated in medicine. Attire is one arena in which this issue plays out, and it’s a “bigger picture” that goes beyond the white coat.

Dr. Jain has been “told by patients that a particular outfit doesn’t make me look like a doctor or that scrubs make me look younger. I don’t think my male colleagues have been subjected to these types of remarks, but my female colleagues have heard them as well.”

Even fellow health care providers have commented on Dr. Jain’s clothing. She was presenting at a major medical conference via video and was wearing a similar outfit to the one she wore for her headshot. “Thirty seconds before beginning my talk, one of the male physicians said: ‘Are you wearing the same outfit you wore for your headshot?’ I can’t imagine a man commenting that another man was wearing the same jacket or tie that he wore in the photograph. I found it odd that this was something that someone felt the need to comment on right before I was about to address a large group of people in a professional capacity.”

Addressing these systemic issues “needs to be done and amplified not only by women but also by men in medicine,” said Dr. Jain, founder and director of  Women in Medicine, an organization consisting of women physicians whose goal is to “find and implement solutions to gender inequity.”

Dr. Jain said the organization offers an Inclusive Leadership Development Lab – a course specifically for men in health care leadership positions to learn how to be more equitable, inclusive leaders.
 

A personal decision

Dr. Pasricha hopes she “handled the patient’s misidentification graciously.” She explained to him that she would be the physician conducting the procedure. The patient was initially “a little embarrassed” that he had misidentified her, but she put him at ease and “we moved forward quickly.”

At this point, although some of her colleagues have continued to wear scrubs or have returned to wearing fleeces with hospital logos, Dr. Pasricha prefers to wear a white coat in both inpatient and outpatient settings because it reduces the likelihood of misidentification.

And white coats can be more convenient – for example, Dr. Jain likes the fact that the white coat has pockets where she can put her stethoscope and other items, while some of her professional clothes don’t always have pockets.

Dr. Jain noted that there are some institutions where everyone seems to wear white coats, not only the physician – “from the chaplain to the phlebotomist to the social worker.” In those settings, the white coat no longer distinguishes physicians from nonphysicians, and so wearing a white coat may not confer additional credibility as a physician.

Nevertheless, “if you want to wear a white coat, if you feel it gives you that added level of authority, if you feel it tells people more clearly that you’re a physician, by all means go ahead and do so,” she said. “There’s no ‘one-size-fits-all’ strategy or solution. What’s more important than your clothing is your professionalism.”

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

Early in the COVID-19 pandemic, Trisha Pasricha, MD, a gastroenterologist and research fellow at Massachusetts General Hospital in Boston, was talking to a patient who had been hospitalized for a peptic ulcer.

Like other physicians in her institution, Dr. Pasricha was wearing scrubs instead of a white coat, out of concern that the white coat might be more prone to accumulating or transmitting COVID-19 pathogens. Her badge identified her as a physician, and she introduced herself clearly as “Dr. Pasricha.”

The patient “required an emergent procedure, which I discussed with him,” Dr. Pasricha told this news organization. “I went over what the procedure entailed, the risks and benefits, and the need for informed consent. The patient nodded and seemed to understand, but at the end of the discussion he said: ‘That all sounds fine, but I need to speak to the doctor first.’ ”

Dr. Pasricha was taken aback. She wondered: “Who did he think I was the whole time that I was reviewing medical concerns, explaining medical concepts, and describing a procedure in a way that a physician would describe it?”

She realized the reason he didn’t correctly identify her was that, clad only in scrubs, she was less easily recognizable as a physician. And while this type of misidentification happened to physicians of both genders wearing scrubs and no white coat, it was more common for female than for male physicians to be misidentified as technicians, nurses, physician assistants, or other health care professionals, according to Dr. Pasricha.

Dr. Pasricha said she has been the recipient of this “implicit bias” not only from patients but also from members of the health care team, and added that other female colleagues have told her that they’ve had similar experiences, especially when they’re not wearing a white coat.
 

Changing times, changing trends

When COVID-19 began to spread, “there was an initial concern that COVID-19 was passed through surfaces, and concerns about whether white coats could carry viral particles,” according to Jordan Steinberg, MD, PhD, surgical director of the craniofacial program at Nicklaus Children’s Pediatric Specialists/Nicklaus Children’s Health System, Miami. “Hospitals didn’t want to launder the white coats as frequently as scrubs, due to cost concerns. There was also a concern raised that a necktie might dangle in patients’ faces, coming in closer contact with pathogens, so more physicians were wearing scrubs.”

Yet even before the pandemic, physician attire in hospital and outpatient settings had started to change. Dr. Steinberg, who is also a clinical associate professor at Florida International University, Miami, told this news organization that, in his previous appointment at Johns Hopkins University, Baltimore, he and his colleagues “had noticed in our institution, as well as other facilities, an increasing trend that moved from white coats worn over professional attire toward more casual dress among medical staff – increased wearing of casual fleece or softshell jackets with the institutional logo.”

This was especially true with trainees and the “younger generation,” who were preferring “what I would almost call ‘warm-up clothes,’ gym clothes, and less shirt-tie-white-coat attire for men or white-coats-and-business attire for women.” Dr. Steinberg thinks that some physicians prefer the fleece with the institutional logo “because it’s like wearing your favorite sports team jersey. It gives a sense of belonging.”

Todd Shaffer, MD, MBA, a family physician at University Physicians Associates, Truman Medical Centers and the Lakewood Medical Pavilion, Kansas City, Mo., has been at his institution for 30 years and has seen a similar trend. “At one point, things were very formal,” he told this news organization. But attire was already becoming less formal before the pandemic, and new changes took place during the pandemic, as physicians began wearing scrubs instead of white coats because of fears of viral contamination.

Now, there is less concern about potential viral contamination with the white coat. Yet many physicians continue to wear scrubs – especially those who interact with patients with COVID – and it has become more acceptable to do so, or to wear personal protective equipment (PPE) over ordinary clothing, but it is less common in routine clinical practice, said Dr. Shaffer, a member of the board of directors of the American Academy of Family Physicians.

“The world has changed since COVID. People feel more comfortable dressing more casually during professional Zoom calls, when they have the convenience of working from home,” said Dr. Shaffer, who is also a professor of family medicine at University of Missouri–Kansas City.

Dr. Shaffer himself hasn’t worn a white coat for years. “I’m more likely to wear medium casual pants. I’ve bought some nicer shirts, so I still look professional and upbeat. I don’t always tuck in my shirt, and I don’t dress as formally.” He wears PPE and a mask and/or face shield when treating patients with COVID-19. And he wears a white coat “when someone wants a photograph taken with the doctors – with the stethoscope draped around my neck.”
 

Traditional symbol of medicine

Because of the changing mores, Dr. Steinberg and colleagues at Johns Hopkins wondered if there might still be a role for professional attire and white coats and what patients prefer. To investigate the question, they surveyed 487 U.S. adults in the spring of 2020.

Respondents were asked where and how frequently they see health care professionals wearing white coats, scrubs, and fleece or softshell jackets. They were also shown photographs depicting models wearing various types of attire commonly seen in health care settings and were asked to rank the “health care provider’s” level of experience, professionalism, and friendliness.

The majority of participants said they had seen health care practitioners in white coats “most of the time,” in scrubs “sometimes,” and in fleece or softshell jackets “rarely.” Models in white coats were regarded by respondents as more experienced and professional, although those in softshell jackets were perceived as friendlier.

There were age as well as regional differences in the responses, Dr. Steinberg said. Older respondents were significantly more likely than their younger counterparts to perceive a model wearing a white coat over business attire as being more experienced, and – in all regions of the United States except the West coast – respondents gave lower professionalism scores to providers wearing fleece jackets with scrubs underneath.

Respondents tended to prefer surgeons wearing a white coat with scrubs underneath, while a white coat over business attire was the preferred dress code for family physicians and dermatologists.

“People tended to respond as if there was a more professional element in the white coat. The age-old symbol of the white coat still marked something important,” Dr. Steinberg said. “Our data suggest that the white coat isn’t ready to die just yet. People still see an air of authority and a traditional symbol of medicine. Nevertheless, I do think it will become less common than it used to be, especially in certain regions of the country.”
 

Organic, subtle changes

Christopher Petrilli, MD, assistant professor at New York University, conducted research in 2018 regarding physician attire by surveying over 4,000 patients in 10 U.S. academic hospitals. His team found that most patients continued to prefer physicians to wear formal attire under a white coat, especially older respondents.

Dr. Petrilli and colleagues have been studying the issue of physician attire since 2015. “The big issue when we did our initial study – which might not be accurate anymore – is that few hospitals actually had a uniform dress code,” said Dr. Petrilli, the medical director of clinical documentation improvement and the clinical lead of value-based medicine at NYU Langone Hospitals. “When we looked at ‘honor roll hospitals’ during our study, we cold-called these hospitals and also looked online for their dress code policies. Except for the Mayo Clinic, hospitals that had dress code policies were more generic.”

For example, the American Medical Association guidance merely states that attire should be “clean, unsoiled, and appropriate to the setting of care” and recommends weighing research findings regarding textile transmission of health care–associated infections when individual institutions determine their dress code policies. The AMA’s last policy discussion took place in 2015 and its guidance has not changed since the pandemic.

Regardless of what institutions and patients prefer, some research suggests that many physicians would prefer to stay with wearing scrubs rather than reverting to the white coat. One study of 151 hospitalists, conducted in Ireland, found that three-quarters wanted scrubs to remain standard attire, despite the fact that close to half had experienced changes in patients› perception in the absence of their white coat and “professional attire.”

Jennifer Workman, MD, assistant professor of pediatrics, division of pediatric critical care, University of Utah, Salt Lake City, said in an interview that, as the pandemic has “waxed and waned, some trends have reverted to what they were prepandemic, but other physicians have stayed with wearing scrubs.”

Much depends on practice setting, said Dr. Workman, who is also the medical director of pediatric sepsis at Intermountain Care. In pediatrics, for example, many physicians prefer not to wear white coats when they are interacting with young children or adolescents.

Like Dr. Shaffer, Dr. Workman has seen changes in physicians’ attire during video meetings, where they often dress more casually, perhaps wearing sweatshirts. And in the hospital, more are continuing to wear scrubs. “But I don’t see it as people trying to consciously experiment or push boundaries,” she said. “I see it as a more organic, subtle shift.”

Dr. Petrilli thinks that, at this juncture, it’s “pretty heterogeneous as to who is going to return to formal attire and a white coat and who won’t.” Further research needs to be done into currently evolving trends. “We need a more thorough survey looking at changes. We need to ask [physician respondents]: ‘What is your current attire, and how has it changed?’ ”
 

Navigating the gender divide

In their study, Dr. Steinberg and colleagues found that respondents perceived a male model wearing business attire underneath any type of outerwear (white coat or fleece) to be significantly more professional than a female model wearing the same attire. Respondents also perceived males wearing scrubs to be more professional than females wearing scrubs.

Male models in white coats over business attire were also more likely to be identified as physicians, compared with female models in the same attire. Females were also more likely to be misidentified as nonphysician health care professionals.

Shikha Jain, MD, assistant professor of medicine at the University of Illinois Cancer Center in Chicago, said that Dr. Steinberg’s study confirmed experiences that she and other female physicians have had. Wearing a white coat makes it more likely that a patient will identify you as a physician, but women are less likely to be identified as physicians, regardless of what they wear.

“I think that individuals of color and especially people with intersectional identities – such as women of color – are even more frequently targeted and stereotyped. Numerous studies have shown that a person of color is less likely to be seen as an authority figure, and studies have shown that physicians of color are less likely to be identified as ‘physicians,’ compared to a Caucasian individual,” she said.

Does that mean that female physicians should revert back to prepandemic white coats rather than scrubs or more casual attire? Not necessarily, according to Dr. Jain.

“The typical dress code guidance is that physicians should dress ‘professionally,’ but what that means is a question that needs to be addressed,” Dr. Jain said. “Medicine has evolved from the days of house calls, in which one’s patient population is a very small, intimate group of people in the physician’s community. Yet now, we’ve given rebirth to the ‘house call’ when we do telemedicine with a patient in his or her home. And in the old days, doctors often had offices their homes and now, with telemedicine, patients often see the interior of their physician’s home.” As the delivery of medicine evolves, concepts of “professionalism” – what is defined as “casual” and what is defined as “formal” – is also evolving.

The more important issue, according to Dr. Jain, is to “continue the conversation” about the discrepancies between how men and women are treated in medicine. Attire is one arena in which this issue plays out, and it’s a “bigger picture” that goes beyond the white coat.

Dr. Jain has been “told by patients that a particular outfit doesn’t make me look like a doctor or that scrubs make me look younger. I don’t think my male colleagues have been subjected to these types of remarks, but my female colleagues have heard them as well.”

Even fellow health care providers have commented on Dr. Jain’s clothing. She was presenting at a major medical conference via video and was wearing a similar outfit to the one she wore for her headshot. “Thirty seconds before beginning my talk, one of the male physicians said: ‘Are you wearing the same outfit you wore for your headshot?’ I can’t imagine a man commenting that another man was wearing the same jacket or tie that he wore in the photograph. I found it odd that this was something that someone felt the need to comment on right before I was about to address a large group of people in a professional capacity.”

Addressing these systemic issues “needs to be done and amplified not only by women but also by men in medicine,” said Dr. Jain, founder and director of  Women in Medicine, an organization consisting of women physicians whose goal is to “find and implement solutions to gender inequity.”

Dr. Jain said the organization offers an Inclusive Leadership Development Lab – a course specifically for men in health care leadership positions to learn how to be more equitable, inclusive leaders.
 

A personal decision

Dr. Pasricha hopes she “handled the patient’s misidentification graciously.” She explained to him that she would be the physician conducting the procedure. The patient was initially “a little embarrassed” that he had misidentified her, but she put him at ease and “we moved forward quickly.”

At this point, although some of her colleagues have continued to wear scrubs or have returned to wearing fleeces with hospital logos, Dr. Pasricha prefers to wear a white coat in both inpatient and outpatient settings because it reduces the likelihood of misidentification.

And white coats can be more convenient – for example, Dr. Jain likes the fact that the white coat has pockets where she can put her stethoscope and other items, while some of her professional clothes don’t always have pockets.

Dr. Jain noted that there are some institutions where everyone seems to wear white coats, not only the physician – “from the chaplain to the phlebotomist to the social worker.” In those settings, the white coat no longer distinguishes physicians from nonphysicians, and so wearing a white coat may not confer additional credibility as a physician.

Nevertheless, “if you want to wear a white coat, if you feel it gives you that added level of authority, if you feel it tells people more clearly that you’re a physician, by all means go ahead and do so,” she said. “There’s no ‘one-size-fits-all’ strategy or solution. What’s more important than your clothing is your professionalism.”

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

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.

“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

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

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.

“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

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

The “twincretin” era for treating patients with type 2 diabetes has begun, with the Food and Drug Administration’s approval of tirzepatide for this indication on May 13, making it the first approved agent that works as a dual agonist for the two principal human incretins.

Tirzepatide represents “an important advance in the treatment of type 2 diabetes,” the FDA’s Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders, and obesity, said in a statement released by the agency.

That advance is based on tirzepatide’s engineering, which gives it agonist properties for both the glucagonlike peptide–1 (GLP-1) receptor, as well as the glucose-dependent insulinotropic polypeptide (GIP). Several agents are already approved for U.S. use from the class with single-agonist activity on the GLP-1 receptor, including semaglutide (Ozempic for treating patients with type 2 diabetes; Wegovy for weight loss).

The FDA’s approved label includes all three dosages of tirzepatide that underwent testing in the pivotal trials: 5 mg, 10 mg, and 15 mg, each delivered by subcutaneous injection once a week. Also approved was the 2.5-mg/week dose used when starting a patient on the agent. Gradual up-titration appears to minimize possible gastrointestinal adverse effects during initial tirzepatide use.

Tirzepatide, which will be marketed by Lilly as Mounjaro, will hit the U.S. market with much anticipation, based on results from five pivotal trials, all reported during the past year or so, that established the drug’s unprecedented efficacy for reducing hemoglobin A1c levels as well as triggering significant weight loss in most patients with a generally benign safety profile.
 

‘Impressive’ effects

The effects from tirzepatide on A1c and weight seen in these studies was “impressive, and will likely drive use of this agent,” commented Carol H. Wysham, MD, an endocrinologist at the MultiCare Rockwood Clinic in Spokane, Wash.

Tirzepatide received good notices in several editorials that accompanied the published reports of the pivotal trials. The first of these, a commentary from two U.K.-based endocrinologists, said that “tirzepatide appears to represent an advancement over current GLP-1 analogues, providing enhanced glycemic and weight benefits without an added penalty in terms of gastrointestinal adverse effects.”

The pivotal trials included head-to-head comparisons between tirzepatide and a 1.0-mg/week dose of semaglutide, as well as comparisons with each of two long-acting insulin analogs, insulin glargine (Lantus) and insulin degludec (Tresiba).

“These are the most important comparators,” Dr. Wysham said.

“Tirzepatide was appropriately compared with the best-in-class and most effective glucose-lowering agents currently available,” said Ildiko Lingvay, MD, an endocrinologist and professor at the University of Texas Southwestern Medical Center in Dallas.

“Given its outstanding efficacy at both lowering glucose and weight, I expect tirzepatide to have quick uptake among patients with diabetes,” Dr. Lingvay said. “The only limiting factor will be cost,” she added in an interview, highlighting the major stumbling block that could limit tirzepatide’s uptake.

“As with any new medication, access will be the biggest barrier to uptake,” agreed Alice Y.Y. Cheng, MD, an endocrinologist at the University of Toronto.
 

Lingering uncertainties

The timing of the comparison with semaglutide leaves some unanswered questions. The SURPASS-2 trial compared the three primary tirzepatide regimens (5 mg, 10 mg, and 15 mg/week) with a 1.0-mg/week dose of semaglutide, which was at the time the only approved dosage of semaglutide for patients with type 2 diabetes. Since then, a 2.0-mg/week dosage of semaglutide (Ozempic) received U.S. approval for treating patients with type 2 diabetes, and a 2.4-mg/week dosage (Wegovy) received an FDA nod for treating people with obesity.

The lack of head-to-head data for tirzepatide against the 2.0-mg/week dose of semaglutide “leaves a clinical gap,” said Dr. Cheng. Tirzepatide “represents an advance over semaglutide at the 1-mg/week dose, but we do not know for sure compared to the higher dose.”

Another important limitation for tirzepatide right now is that the agent’s obligatory cardiovascular outcome trial, SURPASS CVOT, with about 12,500 enrolled patients, will not have findings out until about 2025, leaving uncertainty until then about tirzepatide’s cardiovascular effects.

“We are missing the cardiovascular outcome data – very important data will come” from that trial, noted Dr. Wysham. “There will be some reluctance to use the agent in high-risk patients until we see the results.”

Given tirzepatide’s proven efficacy so far, the missing cardiovascular results “are not a limitation for most patients, but for patients with preexisting cardiovascular disease I will continue to use agents with proven benefits until the SURPASS CVOT results come out,” Dr. Lingvay said.

And then there is the cost issue, something that Lilly had not yet publicly addressed at the time that the FDA announced its decision.

An analysis of cost effectiveness published by the U.S. Institute for Clinical and Economic Review in February 2022 concluded that tirzepatide had a better impact on patient quality of life, compared with 1.0 mg/week semaglutide for treating patients with type 2 diabetes, which gave it a modest pricing cushion, compared with semaglutide of about $5,500 per quality-adjusted life-year gained. But the researchers who prepared the report admitted that tirzepatide’s cost-effectiveness was hard to estimate without knowing the drug’s actual price.  

Dr. Wysham has financial ties to AstraZeneca, Abbott, Boehringer Ingelheim, Intercept, Janssen, Mylan, Novo Nordisk, and Sanofi. Dr. Lingvay has dies to Lilly, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Pfizer, and Mylan, Intarcia, MannKind, Valeritas, and several other drug and device makers.

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

People with nonalcoholic fatty liver disease (NAFLD) and a lean or healthy body mass index are at increased risk for peripheral vascular disease, stroke, and cardiovascular disease, a surprise finding from a new study reveals.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions,” lead researcher Karn Wijarnpreecha, MD, MPH, said during a media briefing that previewed select research for Digestive Disease Week^® (DDW) 2022. “So, we were very surprised to find this link to cardiovascular disease.”

The investigators saw this increased risk of cardiovascular disease despite this group having a lower prevalence of atherosclerotic risk factors and metabolic disease.

This first study of its kind suggests physicians should consider the risk of cardiovascular disease in all patients with NAFLD, not just in those who are overweight or living with obesity – groups traditionally thought to carry more risk.

NAFLD in lean individuals is not a benign disease.

“NAFLD patients with a normal BMI are often overlooked because we assume that the risk for more serious conditions is lower than for those who are overweight or obese. But this way of thinking may be putting these patients at risk,” added Dr. Wijarnpreecha, who is a transplant hepatology fellow at the University of Michigan, Ann Arbor.

Key findings

Approximately 25% of U.S. adults live with NAFLD, an umbrella term for liver conditions in people who drink little to no alcohol. It is characterized by too much fat stored in the liver. Although most people have no symptoms, the condition can lead to other dangerous conditions, such as diabetes, cardiovascular disease, and cirrhosis of the liver, Dr. Wijarnpreecha said.

The investigators retrospectively studied a cohort of 18,793 adults diagnosed with NAFLD at the University of Michigan Hospital from 2012-2021. One aim was to compare the prevalence of cirrhosis, cardiovascular disease, metabolic diseases, and chronic kidney disease in relation to BMI.

They also classified people into four BMI categories: lean, overweight, obesity class 1, and obesity class 2-3.

Compared with non-lean patients, lean patients had a higher prevalence of peripheral arterial disease and stroke and a similar rate of cardiovascular disease based on identification of ICD codes.

Almost 6% of lean patients had peripheral arterial disease, compared with rates of approximately 4%-5% in overweight people and people with obesity. Similarly, more than 6% of the lean group experienced a stroke compared with 5% or less of the other BMI groups.

“We found that lean patients with NAFLD also had a significant higher prevalence of cardiovascular disease, independent of age, sex, race, smoking status, diabetes, hypertension, and dyslipidemia,” Dr. Wijarnpreecha said.

At the same time, compared with non-lean patients, lean patients had a lower prevalence of cirrhosis, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in an analysis that adjusted for confounders.
 

Exploring the unknown

Researchers now have a mystery on their hands: What is causing this unexpected higher risk of cardiovascular disease in lean people with NAFLD?

Loren Laine, MD, chief of the section of digestive diseases at Yale University School of Medicine, New Haven, Conn., and moderator of the media briefing, asked Wijarnpreecha for his leading theory behind this connection.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even gut microbiota,” Dr. Wijarnpreecha replied. “But these are factors that we did not capture from this current study.”

“We are preparing to conduct additional research with longitudinal data to better understand NAFLD in lean patients,” Dr. Wijarnpreecha added.

“It’s an interesting finding, but there are some questions from this retrospective study,” said Arun J. Sanyal, MD, when asked to comment on the study.

Identifying and quantifying any alcohol use, smoking, or hypertension that could also have contributed to increased cardiovascular risk would be useful. Another question relates to how the population with NAFLD was identified. Was NAFLD an incidental finding in their diagnosis, asked Dr. Sanyal, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health at Virginia Commonwealth University, Richmond.

“I’m not dissing the study,” he said, “But like all the observations like this, I think we have to kick the tires.”

It’s an “important new observation” that requires further study to fully understand what it means and what the therapeutic implications might be. It is also important to assess any possible confounders and any causal relationship among these factors, Dr. Sanyal added.

“There’s no question it is important to continue to do these types of studies,” he added. “Through this kind of research we find new things that lead to the science that can then significantly change how we approach these issues.”

A version of this article first appeared on Medscape.com. This article was updated on May 18, 2022.

People with nonalcoholic fatty liver disease (NAFLD) and a lean or healthy body mass index are at increased risk for peripheral vascular disease, stroke, and cardiovascular disease, a surprise finding from a new study reveals.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions,” lead researcher Karn Wijarnpreecha, MD, MPH, said during a media briefing that previewed select research for Digestive Disease Week^® (DDW) 2022. “So, we were very surprised to find this link to cardiovascular disease.”

The investigators saw this increased risk of cardiovascular disease despite this group having a lower prevalence of atherosclerotic risk factors and metabolic disease.

This first study of its kind suggests physicians should consider the risk of cardiovascular disease in all patients with NAFLD, not just in those who are overweight or living with obesity – groups traditionally thought to carry more risk.

NAFLD in lean individuals is not a benign disease.

“NAFLD patients with a normal BMI are often overlooked because we assume that the risk for more serious conditions is lower than for those who are overweight or obese. But this way of thinking may be putting these patients at risk,” added Dr. Wijarnpreecha, who is a transplant hepatology fellow at the University of Michigan, Ann Arbor.

Key findings

Approximately 25% of U.S. adults live with NAFLD, an umbrella term for liver conditions in people who drink little to no alcohol. It is characterized by too much fat stored in the liver. Although most people have no symptoms, the condition can lead to other dangerous conditions, such as diabetes, cardiovascular disease, and cirrhosis of the liver, Dr. Wijarnpreecha said.

The investigators retrospectively studied a cohort of 18,793 adults diagnosed with NAFLD at the University of Michigan Hospital from 2012-2021. One aim was to compare the prevalence of cirrhosis, cardiovascular disease, metabolic diseases, and chronic kidney disease in relation to BMI.

They also classified people into four BMI categories: lean, overweight, obesity class 1, and obesity class 2-3.

Compared with non-lean patients, lean patients had a higher prevalence of peripheral arterial disease and stroke and a similar rate of cardiovascular disease based on identification of ICD codes.

Almost 6% of lean patients had peripheral arterial disease, compared with rates of approximately 4%-5% in overweight people and people with obesity. Similarly, more than 6% of the lean group experienced a stroke compared with 5% or less of the other BMI groups.

“We found that lean patients with NAFLD also had a significant higher prevalence of cardiovascular disease, independent of age, sex, race, smoking status, diabetes, hypertension, and dyslipidemia,” Dr. Wijarnpreecha said.

At the same time, compared with non-lean patients, lean patients had a lower prevalence of cirrhosis, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in an analysis that adjusted for confounders.
 

Exploring the unknown

Researchers now have a mystery on their hands: What is causing this unexpected higher risk of cardiovascular disease in lean people with NAFLD?

Loren Laine, MD, chief of the section of digestive diseases at Yale University School of Medicine, New Haven, Conn., and moderator of the media briefing, asked Wijarnpreecha for his leading theory behind this connection.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even gut microbiota,” Dr. Wijarnpreecha replied. “But these are factors that we did not capture from this current study.”

“We are preparing to conduct additional research with longitudinal data to better understand NAFLD in lean patients,” Dr. Wijarnpreecha added.

“It’s an interesting finding, but there are some questions from this retrospective study,” said Arun J. Sanyal, MD, when asked to comment on the study.

Identifying and quantifying any alcohol use, smoking, or hypertension that could also have contributed to increased cardiovascular risk would be useful. Another question relates to how the population with NAFLD was identified. Was NAFLD an incidental finding in their diagnosis, asked Dr. Sanyal, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health at Virginia Commonwealth University, Richmond.

“I’m not dissing the study,” he said, “But like all the observations like this, I think we have to kick the tires.”

It’s an “important new observation” that requires further study to fully understand what it means and what the therapeutic implications might be. It is also important to assess any possible confounders and any causal relationship among these factors, Dr. Sanyal added.

“There’s no question it is important to continue to do these types of studies,” he added. “Through this kind of research we find new things that lead to the science that can then significantly change how we approach these issues.”

A version of this article first appeared on Medscape.com. This article was updated on May 18, 2022.

People with nonalcoholic fatty liver disease (NAFLD) and a lean or healthy body mass index are at increased risk for peripheral vascular disease, stroke, and cardiovascular disease, a surprise finding from a new study reveals.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions,” lead researcher Karn Wijarnpreecha, MD, MPH, said during a media briefing that previewed select research for Digestive Disease Week^® (DDW) 2022. “So, we were very surprised to find this link to cardiovascular disease.”

The investigators saw this increased risk of cardiovascular disease despite this group having a lower prevalence of atherosclerotic risk factors and metabolic disease.

This first study of its kind suggests physicians should consider the risk of cardiovascular disease in all patients with NAFLD, not just in those who are overweight or living with obesity – groups traditionally thought to carry more risk.

NAFLD in lean individuals is not a benign disease.

“NAFLD patients with a normal BMI are often overlooked because we assume that the risk for more serious conditions is lower than for those who are overweight or obese. But this way of thinking may be putting these patients at risk,” added Dr. Wijarnpreecha, who is a transplant hepatology fellow at the University of Michigan, Ann Arbor.

Key findings

Approximately 25% of U.S. adults live with NAFLD, an umbrella term for liver conditions in people who drink little to no alcohol. It is characterized by too much fat stored in the liver. Although most people have no symptoms, the condition can lead to other dangerous conditions, such as diabetes, cardiovascular disease, and cirrhosis of the liver, Dr. Wijarnpreecha said.

The investigators retrospectively studied a cohort of 18,793 adults diagnosed with NAFLD at the University of Michigan Hospital from 2012-2021. One aim was to compare the prevalence of cirrhosis, cardiovascular disease, metabolic diseases, and chronic kidney disease in relation to BMI.

They also classified people into four BMI categories: lean, overweight, obesity class 1, and obesity class 2-3.

Compared with non-lean patients, lean patients had a higher prevalence of peripheral arterial disease and stroke and a similar rate of cardiovascular disease based on identification of ICD codes.

Almost 6% of lean patients had peripheral arterial disease, compared with rates of approximately 4%-5% in overweight people and people with obesity. Similarly, more than 6% of the lean group experienced a stroke compared with 5% or less of the other BMI groups.

“We found that lean patients with NAFLD also had a significant higher prevalence of cardiovascular disease, independent of age, sex, race, smoking status, diabetes, hypertension, and dyslipidemia,” Dr. Wijarnpreecha said.

At the same time, compared with non-lean patients, lean patients had a lower prevalence of cirrhosis, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in an analysis that adjusted for confounders.
 

Exploring the unknown

Researchers now have a mystery on their hands: What is causing this unexpected higher risk of cardiovascular disease in lean people with NAFLD?

Loren Laine, MD, chief of the section of digestive diseases at Yale University School of Medicine, New Haven, Conn., and moderator of the media briefing, asked Wijarnpreecha for his leading theory behind this connection.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even gut microbiota,” Dr. Wijarnpreecha replied. “But these are factors that we did not capture from this current study.”

“We are preparing to conduct additional research with longitudinal data to better understand NAFLD in lean patients,” Dr. Wijarnpreecha added.

“It’s an interesting finding, but there are some questions from this retrospective study,” said Arun J. Sanyal, MD, when asked to comment on the study.

Identifying and quantifying any alcohol use, smoking, or hypertension that could also have contributed to increased cardiovascular risk would be useful. Another question relates to how the population with NAFLD was identified. Was NAFLD an incidental finding in their diagnosis, asked Dr. Sanyal, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health at Virginia Commonwealth University, Richmond.

“I’m not dissing the study,” he said, “But like all the observations like this, I think we have to kick the tires.”

It’s an “important new observation” that requires further study to fully understand what it means and what the therapeutic implications might be. It is also important to assess any possible confounders and any causal relationship among these factors, Dr. Sanyal added.

“There’s no question it is important to continue to do these types of studies,” he added. “Through this kind of research we find new things that lead to the science that can then significantly change how we approach these issues.”

A version of this article first appeared on Medscape.com. This article was updated on May 18, 2022.

Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) demonstrate highly similar clinical courses and mortality rates, and a name change may not be clinically beneficial, based on data from more than 17,000 patients.

Instead, etiologic subcategorization of fatty liver disease (FLD) should be considered, reported lead author Zobair M. Younossi, MD, of Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Va., and colleagues.

“There is debate about whether NAFLD is an appropriate name as the term ‘non-alcoholic’ overemphasizes the absence of alcohol use and underemphasizes the importance of the metabolic risk factors which are the main drivers of disease progression,” the investigators wrote in Hepatology. “It has been suggested that MAFLD may better reflect these risk factors. However, such a recommendation is made despite a lack of a general consensus on the definition of ‘metabolic health’ and disagreements in endocrinology circles about the term ‘metabolic syndrome.’ Nevertheless, a few investigators have suggested that MAFLD but not NAFLD is associated with increased fibrosis and mortality.”

To look for clinical differences between the two disease entities, Dr. Younossi and colleagues turned to the National Health and Nutrition Examination Survey (NHANES). Specifically, the NHANES III and NHANES 2017-2018 cohorts were employed, including 12,878 and 4,328 participants, respectively.

MAFLD was defined as FLD with overweight/obesity, evidence of metabolic dysregulation, or type 2 diabetes mellitus. NAFLD was defined as FLD without excessive alcohol consumption or other causes of chronic liver disease. Patients were sorted into four groups: NAFLD, MAFLD, both disease types, or neither disease type. Since the categories were not mutually exclusive, the investigators compared clinical characteristics based on 95% confidence intervals. If no overlap was found, then differences were deemed statistically significant.

Diagnoses of NAFLD and MAFLD were highly concordant (kappa coefficient = 0.83-0.94). After a median of 22.8 years follow-up, no significant differences were found between groups for cause-specific mortality, all-cause mortality, or major clinical characteristics except those inherent to the disease definitions (for example, lack of alcohol use in NAFLD). Greatest risk factors for advanced fibrosis in both groups were obesity, high-risk fibrosis, and type 2 diabetes mellitus.

As anticipated, by definition, alcoholic liver disease and excess alcohol use were documented in approximately 15% of patients with MAFLD, but in no patients with NAFLD. As such, alcoholic liver disease predicted liver-specific mortality for MAFLD (hazard ratio, 4.50; 95% confidence interval, 1.89-10.75) but not NAFLD. Conversely, insulin resistance predicted liver-specific mortality in NAFLD (HR, 3.57; 95% CI, 1.35-9.42) but not MAFLD (HR, 0.84; 95% CI, 0.36-1.95).

“These data do not support the notion that a name change from NAFLD to MAFLD will better capture the risk for long-term outcomes of these patients or better define metabolically at-risk patients who present with FLD,” the investigators concluded. “On the other hand, enlarging the definition to FLD with subcategories of ‘alcoholic,’ ‘non-alcoholic,’ ‘drug-induced,’ etc. has merit and needs to be further considered. In this context, a true international consensus group of experts supported by liver and non-liver scientific societies must undertake an evidence-based and comprehensive approach to this issue and assess both the benefits and risks of changing the name.”

According to Rohit Loomba, MD, director of the NAFLD research center and professor of medicine in the division of gastroenterology and hepatology at University of California, San Diego, the study offers a preview of the consequences if NAFLD were changed to MAFLD, most notably by making alcohol a key driver of outcomes.

“If we change the name of a disease entity ... how does that impact natural history?” Dr. Loomba asked in an interview. “This paper gives you an idea. If you start calling it MAFLD, then people are dying from alcohol use, and they’re not dying from what we are currently seeing patients with NAFLD die of.”

He also noted that the name change could disrupt drug development and outcome measures since most drugs currently in development are directed at nonalcoholic steatohepatitis (NASH).

“Is it worth the headache?” Dr. Loomba asked. “How are we going to define NASH-related fibrosis? That probably will remain the same because the therapies that we will use to address that will remain consistent with what we are currently pursuing. ... It’s probably premature to change the nomenclature before assessing the impact on finding new treatment.”

Dr. Younossi disclosed relationships with BMS, Novartis, Gilead, and others. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics.

Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) demonstrate highly similar clinical courses and mortality rates, and a name change may not be clinically beneficial, based on data from more than 17,000 patients.

Instead, etiologic subcategorization of fatty liver disease (FLD) should be considered, reported lead author Zobair M. Younossi, MD, of Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Va., and colleagues.

“There is debate about whether NAFLD is an appropriate name as the term ‘non-alcoholic’ overemphasizes the absence of alcohol use and underemphasizes the importance of the metabolic risk factors which are the main drivers of disease progression,” the investigators wrote in Hepatology. “It has been suggested that MAFLD may better reflect these risk factors. However, such a recommendation is made despite a lack of a general consensus on the definition of ‘metabolic health’ and disagreements in endocrinology circles about the term ‘metabolic syndrome.’ Nevertheless, a few investigators have suggested that MAFLD but not NAFLD is associated with increased fibrosis and mortality.”

To look for clinical differences between the two disease entities, Dr. Younossi and colleagues turned to the National Health and Nutrition Examination Survey (NHANES). Specifically, the NHANES III and NHANES 2017-2018 cohorts were employed, including 12,878 and 4,328 participants, respectively.

MAFLD was defined as FLD with overweight/obesity, evidence of metabolic dysregulation, or type 2 diabetes mellitus. NAFLD was defined as FLD without excessive alcohol consumption or other causes of chronic liver disease. Patients were sorted into four groups: NAFLD, MAFLD, both disease types, or neither disease type. Since the categories were not mutually exclusive, the investigators compared clinical characteristics based on 95% confidence intervals. If no overlap was found, then differences were deemed statistically significant.

Diagnoses of NAFLD and MAFLD were highly concordant (kappa coefficient = 0.83-0.94). After a median of 22.8 years follow-up, no significant differences were found between groups for cause-specific mortality, all-cause mortality, or major clinical characteristics except those inherent to the disease definitions (for example, lack of alcohol use in NAFLD). Greatest risk factors for advanced fibrosis in both groups were obesity, high-risk fibrosis, and type 2 diabetes mellitus.

As anticipated, by definition, alcoholic liver disease and excess alcohol use were documented in approximately 15% of patients with MAFLD, but in no patients with NAFLD. As such, alcoholic liver disease predicted liver-specific mortality for MAFLD (hazard ratio, 4.50; 95% confidence interval, 1.89-10.75) but not NAFLD. Conversely, insulin resistance predicted liver-specific mortality in NAFLD (HR, 3.57; 95% CI, 1.35-9.42) but not MAFLD (HR, 0.84; 95% CI, 0.36-1.95).

“These data do not support the notion that a name change from NAFLD to MAFLD will better capture the risk for long-term outcomes of these patients or better define metabolically at-risk patients who present with FLD,” the investigators concluded. “On the other hand, enlarging the definition to FLD with subcategories of ‘alcoholic,’ ‘non-alcoholic,’ ‘drug-induced,’ etc. has merit and needs to be further considered. In this context, a true international consensus group of experts supported by liver and non-liver scientific societies must undertake an evidence-based and comprehensive approach to this issue and assess both the benefits and risks of changing the name.”

According to Rohit Loomba, MD, director of the NAFLD research center and professor of medicine in the division of gastroenterology and hepatology at University of California, San Diego, the study offers a preview of the consequences if NAFLD were changed to MAFLD, most notably by making alcohol a key driver of outcomes.

“If we change the name of a disease entity ... how does that impact natural history?” Dr. Loomba asked in an interview. “This paper gives you an idea. If you start calling it MAFLD, then people are dying from alcohol use, and they’re not dying from what we are currently seeing patients with NAFLD die of.”

He also noted that the name change could disrupt drug development and outcome measures since most drugs currently in development are directed at nonalcoholic steatohepatitis (NASH).

“Is it worth the headache?” Dr. Loomba asked. “How are we going to define NASH-related fibrosis? That probably will remain the same because the therapies that we will use to address that will remain consistent with what we are currently pursuing. ... It’s probably premature to change the nomenclature before assessing the impact on finding new treatment.”

Dr. Younossi disclosed relationships with BMS, Novartis, Gilead, and others. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics.

Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) demonstrate highly similar clinical courses and mortality rates, and a name change may not be clinically beneficial, based on data from more than 17,000 patients.

Instead, etiologic subcategorization of fatty liver disease (FLD) should be considered, reported lead author Zobair M. Younossi, MD, of Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Va., and colleagues.

“There is debate about whether NAFLD is an appropriate name as the term ‘non-alcoholic’ overemphasizes the absence of alcohol use and underemphasizes the importance of the metabolic risk factors which are the main drivers of disease progression,” the investigators wrote in Hepatology. “It has been suggested that MAFLD may better reflect these risk factors. However, such a recommendation is made despite a lack of a general consensus on the definition of ‘metabolic health’ and disagreements in endocrinology circles about the term ‘metabolic syndrome.’ Nevertheless, a few investigators have suggested that MAFLD but not NAFLD is associated with increased fibrosis and mortality.”

To look for clinical differences between the two disease entities, Dr. Younossi and colleagues turned to the National Health and Nutrition Examination Survey (NHANES). Specifically, the NHANES III and NHANES 2017-2018 cohorts were employed, including 12,878 and 4,328 participants, respectively.

MAFLD was defined as FLD with overweight/obesity, evidence of metabolic dysregulation, or type 2 diabetes mellitus. NAFLD was defined as FLD without excessive alcohol consumption or other causes of chronic liver disease. Patients were sorted into four groups: NAFLD, MAFLD, both disease types, or neither disease type. Since the categories were not mutually exclusive, the investigators compared clinical characteristics based on 95% confidence intervals. If no overlap was found, then differences were deemed statistically significant.

Diagnoses of NAFLD and MAFLD were highly concordant (kappa coefficient = 0.83-0.94). After a median of 22.8 years follow-up, no significant differences were found between groups for cause-specific mortality, all-cause mortality, or major clinical characteristics except those inherent to the disease definitions (for example, lack of alcohol use in NAFLD). Greatest risk factors for advanced fibrosis in both groups were obesity, high-risk fibrosis, and type 2 diabetes mellitus.

As anticipated, by definition, alcoholic liver disease and excess alcohol use were documented in approximately 15% of patients with MAFLD, but in no patients with NAFLD. As such, alcoholic liver disease predicted liver-specific mortality for MAFLD (hazard ratio, 4.50; 95% confidence interval, 1.89-10.75) but not NAFLD. Conversely, insulin resistance predicted liver-specific mortality in NAFLD (HR, 3.57; 95% CI, 1.35-9.42) but not MAFLD (HR, 0.84; 95% CI, 0.36-1.95).

“These data do not support the notion that a name change from NAFLD to MAFLD will better capture the risk for long-term outcomes of these patients or better define metabolically at-risk patients who present with FLD,” the investigators concluded. “On the other hand, enlarging the definition to FLD with subcategories of ‘alcoholic,’ ‘non-alcoholic,’ ‘drug-induced,’ etc. has merit and needs to be further considered. In this context, a true international consensus group of experts supported by liver and non-liver scientific societies must undertake an evidence-based and comprehensive approach to this issue and assess both the benefits and risks of changing the name.”

According to Rohit Loomba, MD, director of the NAFLD research center and professor of medicine in the division of gastroenterology and hepatology at University of California, San Diego, the study offers a preview of the consequences if NAFLD were changed to MAFLD, most notably by making alcohol a key driver of outcomes.

“If we change the name of a disease entity ... how does that impact natural history?” Dr. Loomba asked in an interview. “This paper gives you an idea. If you start calling it MAFLD, then people are dying from alcohol use, and they’re not dying from what we are currently seeing patients with NAFLD die of.”

He also noted that the name change could disrupt drug development and outcome measures since most drugs currently in development are directed at nonalcoholic steatohepatitis (NASH).

“Is it worth the headache?” Dr. Loomba asked. “How are we going to define NASH-related fibrosis? That probably will remain the same because the therapies that we will use to address that will remain consistent with what we are currently pursuing. ... It’s probably premature to change the nomenclature before assessing the impact on finding new treatment.”

Dr. Younossi disclosed relationships with BMS, Novartis, Gilead, and others. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, and Viking Therapeutics.

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (10⁹/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (10⁹/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (10⁹/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

Treatment with the diabetes drug exenatide was associated with a significant decrease in hyperglycemia in acute stroke patients, a new study shows.

The research could offer clinicians an alternative to insulin therapy to treat hyperglycemia and reduce glucose levels, which are elevated in up to 60% of stroke patients and associated with worse outcomes after stroke.

“Use of these diabetes drugs to control glucose in acute stroke has enormous potential,” said lead researcher Christopher Bladin, PhD, professor of neurology at Monash University and Eastern Health Clinical School, Australia.

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022 annual meeting in Lyon, France.
 

A better fix than insulin?

Hyperglycemia is common in stroke patients, including those who have no prior history of diabetes. Among stroke patients with normal blood glucose upon admission, about 30% will develop hyperglycemia within 48 hours of stroke onset.

Previous research suggests that hyperglycemia is a poor prognostic factor in patients with stroke and may reduce the efficacy of reperfusion therapies such as thrombolysis and mechanical thrombectomy.

“We’ve been looking for different ways of treating hyperglycemia for quite some time, and one of the obvious ways is to use insulin therapy,” Dr. Bladin said. “But as we’ve seen from multiple studies, insulin therapy is difficult.”

Insulin treatment is resource-heavy, significantly increases the risk for hypoglycemia, and some studies suggest the therapy isn’t associated with better outcomes.

An advantage to a GLP-1 agonist-like exenatide, Dr. Bladin added, is that it’s glucose-dependent. As the glucose level falls, the drug’s efficacy diminishes. It is delivered via an autoinjector and easy to administer.

A case for more study

To study exenatide’s efficacy in reducing hyperglycemia and improving neurologic outcomes, researchers developed the phase 2, international, multicenter, randomized controlled TEXAIS trial.

The study enrolled 350 patients following an ischemic stroke. Within 9 hours of stroke onset, patients received either standard care or a subcutaneous injection of 5 mg of exenatide twice daily for 5 days.

On admission, 42% of patients had hyperglycemia, defined as blood glucose > 7.0 mmol/L.

The study’s primary outcome was at least an 8-point improvement in National Institutes of Health Stroke Scale (NIHSS) score by 7 days after treatment with exenatide. Although there was a trend toward better scores with exenatide, the score was not significantly different between groups (56.7% with standard care versus 61.2% with exenatide; adjusted odds ratio, 1.22; P = .38).

However, when the researchers examined hyperglycemia frequency, they found significantly lower incidence in patients treated with exenatide (P = .002).

There were no cases of hypoglycemia in either group, and only 4% of the study group reported nausea or vomiting.

“Clearly exenatide is having some benefit in terms of keeping glucose under control, reducing hyperglycemia,” Dr. Bladin said. “It certainly lends itself to a larger phase 3 study which can look at this more completely.”
 

Value to clinicians

Commenting on the findings, Yvonne Chun, PhD, honorary senior clinical lecturer at University of Edinburgh, noted that, even though the study didn’t find a significant association with improved neurological outcomes, the reduced risk for hypoglycemia makes exenatide an attractive alternative to insulin therapy in stroke patients.

“The results are of value to clinicians, as exenatide could potentially be a safer medication to administer than an insulin infusion in acute stroke patients with hyperglycemia,” Dr. Chun said. “There is less risk of hypoglycemia with exenatide compared to standard care.”

However, Dr. Chun noted that more study is needed before exenatide can replace standard care. Dr. Bladin agrees and would like to pursue a phase 3 trial with a modified design to answer questions raised by Dr. Chun and others.

“The next phase could consider changing the primary outcome to an ordinal shift analysis on modified Rankin Scale – a very commonly used primary outcome in stroke clinical trials to assess improvement in disability,” Dr. Chun said. “The primary outcome used in the presented trial – an 8-point improvement on NIHSS – seemed too ambitious and does not inform disability of the patient post stroke.”

Dr. Bladin said he would also like to see the next phase enroll more patients, examine a higher dose of exenatide, and include better stratification of patients with a history of diabetes. Such a trial could yield findings demonstrating the drug’s effectiveness at reducing hyperglycemia and improving outcomes after stroke, he said.

“I can see the day patients will come in with acute stroke, and as they’re coming into the emergency department, they’ll simply get their shot of exenatide because we know it’s safe to use, and it doesn’t cause hypoglycemia,” Dr. Bladin said. “And from the moment that patient arrives the glucose control is underway.”

Dr. Bladin and Dr. Chun reported no relevant financial relationships. Study funding was not disclosed.

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

I want to talk about a new continuous glucose monitoring (CGM) metric known as glycemic risk index, or GRI. You may ask why we need another metric. We currently have multiple CGM metrics, including time in range, time below range, time above range, mean glucose, glucose management indicator (GMI), and coefficient of variation, and it seems like an overwhelming number of ways to look at the same data.

The problem is that no single metric tells you exactly what is happening with the patient. For instance, a patient could be at a target time in range of 70%, but that could mean that 30% of that patient’s time is spent too low or even very low, which is a very serious problem, versus if 30% of their time was spent in a somewhat but not very high range, which requires less immediate attention.

Dr. David Klonoff and colleagues, including me, decided to see if one number could be used to identify which patients needed more immediate attention and which needed less. He asked 330 clinicians to evaluate 225 CGM tracings and rank their clinical status in terms of these metrics: very low glucose and low glucose hypoglycemia, very high glucose and high glucose hyperglycemia, time in range, mean glucose, and coefficient of variation.

Then he took all the data and analyzed it in complex ways that I barely understood and came up with one number, the GRI, that captures what the clinicians considered important. The analysis showed that the clinician rankings depended primarily on two components: One related to hypoglycemia, which gives more weight to very low glucose than to low glucose hypoglycemia; and the other related to hyperglycemia, which gives greater weight to very high glucose than to high glucose.

These two components were combined into a single glycemic risk index, the GRI, that corresponds closely to the clinician rankings of the overall quality of glycemia. In terms of numbers, the best GRI is in the zero to 20th percentile and the worst in the 81st to 100th percentile. The GRI grid that is provided in the paper enables users to track sequential changes within an individual over time and compare groups of individuals.

As I said initially, at first I wasn’t sure of the utility of adding yet another number to the mix, but I realized that for triaging what I hope will be increasing amounts of CGM data in a health care system, this could help identify those patients who need the most urgent assistance. It can also help providers have an overall sense of how a patient is doing and whether or not they are improving.

The GRI is not yet in general use and needs to be studied to see if it is actually helpful in clinical practice; however, I like the concept. Given the need to increase provider understanding of CGM metrics overall, I think it is a good way for providers to identify which patients need further analysis of their CGM data for potential treatment modifications.

Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies.

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

I want to talk about a new continuous glucose monitoring (CGM) metric known as glycemic risk index, or GRI. You may ask why we need another metric. We currently have multiple CGM metrics, including time in range, time below range, time above range, mean glucose, glucose management indicator (GMI), and coefficient of variation, and it seems like an overwhelming number of ways to look at the same data.

The problem is that no single metric tells you exactly what is happening with the patient. For instance, a patient could be at a target time in range of 70%, but that could mean that 30% of that patient’s time is spent too low or even very low, which is a very serious problem, versus if 30% of their time was spent in a somewhat but not very high range, which requires less immediate attention.

Dr. David Klonoff and colleagues, including me, decided to see if one number could be used to identify which patients needed more immediate attention and which needed less. He asked 330 clinicians to evaluate 225 CGM tracings and rank their clinical status in terms of these metrics: very low glucose and low glucose hypoglycemia, very high glucose and high glucose hyperglycemia, time in range, mean glucose, and coefficient of variation.

Then he took all the data and analyzed it in complex ways that I barely understood and came up with one number, the GRI, that captures what the clinicians considered important. The analysis showed that the clinician rankings depended primarily on two components: One related to hypoglycemia, which gives more weight to very low glucose than to low glucose hypoglycemia; and the other related to hyperglycemia, which gives greater weight to very high glucose than to high glucose.

These two components were combined into a single glycemic risk index, the GRI, that corresponds closely to the clinician rankings of the overall quality of glycemia. In terms of numbers, the best GRI is in the zero to 20th percentile and the worst in the 81st to 100th percentile. The GRI grid that is provided in the paper enables users to track sequential changes within an individual over time and compare groups of individuals.

As I said initially, at first I wasn’t sure of the utility of adding yet another number to the mix, but I realized that for triaging what I hope will be increasing amounts of CGM data in a health care system, this could help identify those patients who need the most urgent assistance. It can also help providers have an overall sense of how a patient is doing and whether or not they are improving.

The GRI is not yet in general use and needs to be studied to see if it is actually helpful in clinical practice; however, I like the concept. Given the need to increase provider understanding of CGM metrics overall, I think it is a good way for providers to identify which patients need further analysis of their CGM data for potential treatment modifications.

Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies.

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

I want to talk about a new continuous glucose monitoring (CGM) metric known as glycemic risk index, or GRI. You may ask why we need another metric. We currently have multiple CGM metrics, including time in range, time below range, time above range, mean glucose, glucose management indicator (GMI), and coefficient of variation, and it seems like an overwhelming number of ways to look at the same data.

The problem is that no single metric tells you exactly what is happening with the patient. For instance, a patient could be at a target time in range of 70%, but that could mean that 30% of that patient’s time is spent too low or even very low, which is a very serious problem, versus if 30% of their time was spent in a somewhat but not very high range, which requires less immediate attention.

Dr. David Klonoff and colleagues, including me, decided to see if one number could be used to identify which patients needed more immediate attention and which needed less. He asked 330 clinicians to evaluate 225 CGM tracings and rank their clinical status in terms of these metrics: very low glucose and low glucose hypoglycemia, very high glucose and high glucose hyperglycemia, time in range, mean glucose, and coefficient of variation.

Then he took all the data and analyzed it in complex ways that I barely understood and came up with one number, the GRI, that captures what the clinicians considered important. The analysis showed that the clinician rankings depended primarily on two components: One related to hypoglycemia, which gives more weight to very low glucose than to low glucose hypoglycemia; and the other related to hyperglycemia, which gives greater weight to very high glucose than to high glucose.

These two components were combined into a single glycemic risk index, the GRI, that corresponds closely to the clinician rankings of the overall quality of glycemia. In terms of numbers, the best GRI is in the zero to 20th percentile and the worst in the 81st to 100th percentile. The GRI grid that is provided in the paper enables users to track sequential changes within an individual over time and compare groups of individuals.

As I said initially, at first I wasn’t sure of the utility of adding yet another number to the mix, but I realized that for triaging what I hope will be increasing amounts of CGM data in a health care system, this could help identify those patients who need the most urgent assistance. It can also help providers have an overall sense of how a patient is doing and whether or not they are improving.

The GRI is not yet in general use and needs to be studied to see if it is actually helpful in clinical practice; however, I like the concept. Given the need to increase provider understanding of CGM metrics overall, I think it is a good way for providers to identify which patients need further analysis of their CGM data for potential treatment modifications.

Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies.

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

After hospitalization, COVID-19 patients 9 hours per day of sedentary time at 3-6 months after discharge, according to data from 37 individuals.

COVID-19 patients experience a wide range of clinical manifestations, and roughly half of those who were hospitalized for COVID-19 report persisting symptoms both physical and mental up to a year after discharge, Bram van Bakel, MD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in a presentation at the presentation at the annual congress of the European Association of Preventive Cardiology.

However, data on physical activity patterns and the impact on recovery after postinfection hospital discharge are limited, he said. Dr. van Bakel and colleagues aimed to assess physical activity, sedentary behavior, and sleep duration in COVID-19 patients at 3-6 months after hospital discharge to explore the association with patient characteristics, disease severity and cardiac dysfunction.

“We hypothesized that COVID-19 survivors will demonstrate low volumes of physical activity and a high sedentary time, especially those with a more severe disease course,” such as longer hospital duration and admission to intensive care, cardiac dysfunction, and persistent symptoms at 3-6 months post discharge, he said.

Dr. van Bakel and colleagues enrolled 37 adult patients in a cross-sectional cohort study. They objectively assessed physical activity, sedentary behavior, and sleep duration for 24 hrs/day during 8 subsequent days in COVID-19 survivors at 3-6 months post hospitalization. The average age of the patients was 60 years, 78% were male, and the average assessment time was 125 days after hospital discharge.

The researchers compared activity patterns based on patient and disease characteristics, cardiac biomarker release during hospitalization, abnormal transthoracic echocardiogram regarding left and right ventricular function and volumes at 3-6 months of follow-up, and the persistence of symptoms after discharge.

Overall, patients spent a median of 4.2 hours per day in light-intensity physical activity, and 1 hour per day in moderate to vigorous physical activity. The overall median time spent sitting was 9.8 hours per day; this was accumulated in approximately 6 prolonged sitting periods of 30 minutes or more and 41.1 short sitting periods of less than 30 minutes.

The median sleep duration was 9.8 hours per day; sleep duration was significantly higher in women, compared with men (9.2 vs. 8.5 hours/day; P = .03), and in patients with persistent symptoms, compared with those without persistent symptoms (9.1 hrs/day vs. 8.3 hrs/day; P = .02). No other differences in activity or sitting patterns appeared among subgroups. Sedentary time of 10 hours or more per day overall puts individuals at increased risk for detrimental health effects, Dr. van Bakel said.

The study findings were limited by the small sample and cross-sectional design, he noted.

However, the results suggest that COVID-19 patients spent most of their time sedentary within the first 3-6 months after hospital discharge. The similar activity patterns across subgroups support a uniform approach to rehabilitation for these patients to target persisting symptoms and prevent long-term health consequences, said Dr. van Bakel. Further studies are warranted in a larger cohort with a prospective design and longitudinal follow-up.

The current study “highlights the need for ongoing rehabilitation in severe COVID-19 survivors after hospitalization to restore premorbid function and endurance,” Alba Miranda Azola, MD, of Johns Hopkins University, Baltimore, said in an interview.

“The findings regarding inactivity are not surprising,” said Dr. Azola. “Immobility during hospitalization results in muscle atrophy and marked decreased endurance. The need for prolonged use of sedation and paralytics during intensive care stays of severe COVID-19 patients is associated with critical illness myopathy. Also, many patients continue to experience hypoxia and dyspnea on exertion for several months after leaving the hospital. The functional impairments and limited activity tolerance often preclude patients from engaging on outpatient rehabilitation programs.

“I do think it surprising that the level of inactivity observed was independent of disease severity and patient factors, but it definitely speaks to the importance of establishing post hospitalization follow-up care that focuses on restoring function and mobility,” Dr. Azola noted.

The study findings may have long-term clinical implications, as COVID-19 survivors who experience functional decline that limits activity and who continue to lead a sedentary lifestyle may be at increased risk for health issues such as heart disease and type 2 diabetes, Dr. Azola said. 

Rigorous research is needed to study the functional and health impact of rehabilitation interventions during and after hospitalization, she emphasized. “Additionally, studies are needed on innovative rehabilitation interventions that improve accessibility to services to patients.”

The study received no outside funding. The researchers and Dr. Azola had no financial conflicts to disclose. Dr. Azola had no financial conflicts to disclose.

After hospitalization, COVID-19 patients 9 hours per day of sedentary time at 3-6 months after discharge, according to data from 37 individuals.

COVID-19 patients experience a wide range of clinical manifestations, and roughly half of those who were hospitalized for COVID-19 report persisting symptoms both physical and mental up to a year after discharge, Bram van Bakel, MD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in a presentation at the presentation at the annual congress of the European Association of Preventive Cardiology.

However, data on physical activity patterns and the impact on recovery after postinfection hospital discharge are limited, he said. Dr. van Bakel and colleagues aimed to assess physical activity, sedentary behavior, and sleep duration in COVID-19 patients at 3-6 months after hospital discharge to explore the association with patient characteristics, disease severity and cardiac dysfunction.

“We hypothesized that COVID-19 survivors will demonstrate low volumes of physical activity and a high sedentary time, especially those with a more severe disease course,” such as longer hospital duration and admission to intensive care, cardiac dysfunction, and persistent symptoms at 3-6 months post discharge, he said.

Dr. van Bakel and colleagues enrolled 37 adult patients in a cross-sectional cohort study. They objectively assessed physical activity, sedentary behavior, and sleep duration for 24 hrs/day during 8 subsequent days in COVID-19 survivors at 3-6 months post hospitalization. The average age of the patients was 60 years, 78% were male, and the average assessment time was 125 days after hospital discharge.

The researchers compared activity patterns based on patient and disease characteristics, cardiac biomarker release during hospitalization, abnormal transthoracic echocardiogram regarding left and right ventricular function and volumes at 3-6 months of follow-up, and the persistence of symptoms after discharge.

Overall, patients spent a median of 4.2 hours per day in light-intensity physical activity, and 1 hour per day in moderate to vigorous physical activity. The overall median time spent sitting was 9.8 hours per day; this was accumulated in approximately 6 prolonged sitting periods of 30 minutes or more and 41.1 short sitting periods of less than 30 minutes.

The median sleep duration was 9.8 hours per day; sleep duration was significantly higher in women, compared with men (9.2 vs. 8.5 hours/day; P = .03), and in patients with persistent symptoms, compared with those without persistent symptoms (9.1 hrs/day vs. 8.3 hrs/day; P = .02). No other differences in activity or sitting patterns appeared among subgroups. Sedentary time of 10 hours or more per day overall puts individuals at increased risk for detrimental health effects, Dr. van Bakel said.

The study findings were limited by the small sample and cross-sectional design, he noted.

However, the results suggest that COVID-19 patients spent most of their time sedentary within the first 3-6 months after hospital discharge. The similar activity patterns across subgroups support a uniform approach to rehabilitation for these patients to target persisting symptoms and prevent long-term health consequences, said Dr. van Bakel. Further studies are warranted in a larger cohort with a prospective design and longitudinal follow-up.

The current study “highlights the need for ongoing rehabilitation in severe COVID-19 survivors after hospitalization to restore premorbid function and endurance,” Alba Miranda Azola, MD, of Johns Hopkins University, Baltimore, said in an interview.

“The findings regarding inactivity are not surprising,” said Dr. Azola. “Immobility during hospitalization results in muscle atrophy and marked decreased endurance. The need for prolonged use of sedation and paralytics during intensive care stays of severe COVID-19 patients is associated with critical illness myopathy. Also, many patients continue to experience hypoxia and dyspnea on exertion for several months after leaving the hospital. The functional impairments and limited activity tolerance often preclude patients from engaging on outpatient rehabilitation programs.

“I do think it surprising that the level of inactivity observed was independent of disease severity and patient factors, but it definitely speaks to the importance of establishing post hospitalization follow-up care that focuses on restoring function and mobility,” Dr. Azola noted.

The study findings may have long-term clinical implications, as COVID-19 survivors who experience functional decline that limits activity and who continue to lead a sedentary lifestyle may be at increased risk for health issues such as heart disease and type 2 diabetes, Dr. Azola said. 

Rigorous research is needed to study the functional and health impact of rehabilitation interventions during and after hospitalization, she emphasized. “Additionally, studies are needed on innovative rehabilitation interventions that improve accessibility to services to patients.”

The study received no outside funding. The researchers and Dr. Azola had no financial conflicts to disclose. Dr. Azola had no financial conflicts to disclose.

After hospitalization, COVID-19 patients 9 hours per day of sedentary time at 3-6 months after discharge, according to data from 37 individuals.

COVID-19 patients experience a wide range of clinical manifestations, and roughly half of those who were hospitalized for COVID-19 report persisting symptoms both physical and mental up to a year after discharge, Bram van Bakel, MD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in a presentation at the presentation at the annual congress of the European Association of Preventive Cardiology.

However, data on physical activity patterns and the impact on recovery after postinfection hospital discharge are limited, he said. Dr. van Bakel and colleagues aimed to assess physical activity, sedentary behavior, and sleep duration in COVID-19 patients at 3-6 months after hospital discharge to explore the association with patient characteristics, disease severity and cardiac dysfunction.

“We hypothesized that COVID-19 survivors will demonstrate low volumes of physical activity and a high sedentary time, especially those with a more severe disease course,” such as longer hospital duration and admission to intensive care, cardiac dysfunction, and persistent symptoms at 3-6 months post discharge, he said.

Dr. van Bakel and colleagues enrolled 37 adult patients in a cross-sectional cohort study. They objectively assessed physical activity, sedentary behavior, and sleep duration for 24 hrs/day during 8 subsequent days in COVID-19 survivors at 3-6 months post hospitalization. The average age of the patients was 60 years, 78% were male, and the average assessment time was 125 days after hospital discharge.

The researchers compared activity patterns based on patient and disease characteristics, cardiac biomarker release during hospitalization, abnormal transthoracic echocardiogram regarding left and right ventricular function and volumes at 3-6 months of follow-up, and the persistence of symptoms after discharge.

Overall, patients spent a median of 4.2 hours per day in light-intensity physical activity, and 1 hour per day in moderate to vigorous physical activity. The overall median time spent sitting was 9.8 hours per day; this was accumulated in approximately 6 prolonged sitting periods of 30 minutes or more and 41.1 short sitting periods of less than 30 minutes.

The median sleep duration was 9.8 hours per day; sleep duration was significantly higher in women, compared with men (9.2 vs. 8.5 hours/day; P = .03), and in patients with persistent symptoms, compared with those without persistent symptoms (9.1 hrs/day vs. 8.3 hrs/day; P = .02). No other differences in activity or sitting patterns appeared among subgroups. Sedentary time of 10 hours or more per day overall puts individuals at increased risk for detrimental health effects, Dr. van Bakel said.

The study findings were limited by the small sample and cross-sectional design, he noted.

However, the results suggest that COVID-19 patients spent most of their time sedentary within the first 3-6 months after hospital discharge. The similar activity patterns across subgroups support a uniform approach to rehabilitation for these patients to target persisting symptoms and prevent long-term health consequences, said Dr. van Bakel. Further studies are warranted in a larger cohort with a prospective design and longitudinal follow-up.

The current study “highlights the need for ongoing rehabilitation in severe COVID-19 survivors after hospitalization to restore premorbid function and endurance,” Alba Miranda Azola, MD, of Johns Hopkins University, Baltimore, said in an interview.

“The findings regarding inactivity are not surprising,” said Dr. Azola. “Immobility during hospitalization results in muscle atrophy and marked decreased endurance. The need for prolonged use of sedation and paralytics during intensive care stays of severe COVID-19 patients is associated with critical illness myopathy. Also, many patients continue to experience hypoxia and dyspnea on exertion for several months after leaving the hospital. The functional impairments and limited activity tolerance often preclude patients from engaging on outpatient rehabilitation programs.

“I do think it surprising that the level of inactivity observed was independent of disease severity and patient factors, but it definitely speaks to the importance of establishing post hospitalization follow-up care that focuses on restoring function and mobility,” Dr. Azola noted.

The study findings may have long-term clinical implications, as COVID-19 survivors who experience functional decline that limits activity and who continue to lead a sedentary lifestyle may be at increased risk for health issues such as heart disease and type 2 diabetes, Dr. Azola said. 

Rigorous research is needed to study the functional and health impact of rehabilitation interventions during and after hospitalization, she emphasized. “Additionally, studies are needed on innovative rehabilitation interventions that improve accessibility to services to patients.”

The study received no outside funding. The researchers and Dr. Azola had no financial conflicts to disclose. Dr. Azola had no financial conflicts to disclose.