MDedge Endocrinology

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

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

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

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

STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.

Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.

Balkonsky/Thinkstock

Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.

Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.

However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).

Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.

“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.

“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
 

Study across 27 sites in India

Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care.  Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.

Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m² and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm², two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.

After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).

Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.

The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.

The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.

Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.

Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
 

50% more patients on esmolol had complete ulcer closure

The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).  

“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).

Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).

The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.

In wounds less than 5 cm², the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm², these proportions were 47.6% vs. 26.9%.

Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.

Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.

Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
 

A class effect of beta blockers?

The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).

Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.

“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.

Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.

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

In a small cross-sectional study of 10- to 16-year-old girls with and without type 1 diabetes, both groups were equally physically active, based on their replies to the bone-specific physical activity questionnaire (BPAQ).

However, among the more sedentary girls (with BPAQ scores below the median), those with type 1 diabetes had worse markers of bone health in imaging tests compared with the girls without diabetes.

“The deleterious effect of [type 1 diabetes] on bone health in girls is most pronounced in those with less weight-bearing activity,” the researchers summarize in a poster presented at the annual meeting of the American Society of Bone and Mineral Research.

However, this is early research and further study is needed, the group cautions.

“Ongoing studies with objective measures of physical activity as well as interventional studies will clarify whether increasing physical activity may improve bone health and reduce fracture risk in this vulnerable group,” they conclude.

“If you look at the sedentary kids, there’s a big discrepancy between the kids who have diabetes and the control kids, and that’s if we’re looking at radius or tibia or trabecular bone density or estimated failure load,” senior author Deborah M. Mitchell, MD, said in an interview at the poster session.

However, “when we look at the kids who are more physically active, we’re really not seeing as much difference [in bone health] between the kids with and without diabetes,” said Dr. Mitchell, a pediatric endocrinologist at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

But she also acknowledged, “There’s all sorts of caveats, including that this is retrospective questionnaire data.”

However, if further, rigorous studies confirm these findings, “physical activity is potentially a really effective means of improving bone quality in kids with type 1 diabetes.”

“This study suggests that bone-loading physical activity can substantially improve skeletal health in children with [type 1 diabetes] and should provide hope for patients and their families that they can take some action to prevent or mitigate the effects of diabetes on bone,” coauthor and incoming ASBMR President Mary L. Bouxsein, PhD, told this news organization in an email.

“We interpret these data as an important reason to advocate for increased time in moderate to vigorous bone-loading activity,” said Dr. Bouxsein, professor, department of orthopedic surgery, Harvard Medical School, Boston, “though the ‘dose’ in terms of hours per day or episodes per week to promote optimal bone health is still to be determined.”
 

“Ongoing debate,” “need stronger proof”

Asked for comment, Laura K. Bachrach, MD, who was not involved with the research, noted: “Activity benefits the development of bone strength through effects on bone geometry more than ‘density,’ and conversely, lack of physical activity can compromise gains in cortical bone diameter and thickness.”

However, “there is ongoing debate about the impact of type 1 diabetes on bone health and the factor(s) determining risk,” Dr. Bachrach, a pediatric endocrinologist at Stanford Children’s Health, Palo Alto, Calif., told this news organization in an email.  

The current findings suggest “that physical activity in adolescent girls provided protection against potential adverse effects of type 1 diabetes,” said Dr. Bachrach, who spoke about bone fragility in childhood in a video commentary in 2021.

Study strengths, she noted, “include the rigor and expertise of the investigators, use of multiple surrogate measures that capture bone geometry/microarchitecture, as well as the inclusion of healthy local controls.”  

“The study is limited by the cross-sectional design and subjects who opted, or not, to be active,” she added. “Stronger proof of the protective effects of activity on bone health in type 1 diabetes would require a randomized longitudinal intervention study, as alluded to by the authors of the study.”
 

Hypothesis: Those with type 1 diabetes acquire less bone mass in early 20s

The excess fracture risk in children with type 1 diabetes has been previously reported and is 14%-35% higher than the fracture risk in children without diabetes, Dr. Bouxsein explained. And “between 30% to 50% of kids [with type 1 diabetes] will have a fracture before the age of 18, so the excess fracture risk in diabetes is not clinically obvious,” she added.

However, “several lines of evidence strongly suggest that bone mass and microarchitecture at the time of peak bone mass (early 20s) is a major determinant of fracture risk throughout the lifespan,” she noted.

“Our hypothesis,” Dr. Bouxsein said, “is that the metabolic disruptions of diabetes, when they are present during the acquisition of peak bone mass, interfere with optimal bone development, and therefore may contribute to increased fracture risk later in life.”

Dr. Bachrach agreed that “peak bone strength is achieved by early adulthood, making childhood and adolescence important times to optimize bone health,” and that “peak bone strength is a predictor of lifetime risk of osteoporosis.”

“The diagnosis of pediatric osteoporosis is made when a child or teen sustains a vertebral fracture or femur fracture with minimal or no trauma,” she explained. “The diagnosis can also be made in a pediatric patient with low BMD [bone mineral density] for age in combination with a history of several long-bone fractures.”

Dr. Mitchell noted that type 1 diabetes is associated with a higher risk of fractures, which is sixfold in adults. In another study, she said, the group showed that in 10- to 16-year-old girls who’ve only had diabetes for a few years, “trabecular bone density is lower, they have lower estimated failure load, and longitudinally when we follow them, at least at the radius, we’re seeing bone loss at a relatively young age when we wouldn’t be expecting to see bone loss.”
 

80 girls enrolled, half had type 1 diabetes

Researchers enrolled 36 girls with type 1 diabetes and 44 girls without type 1 diabetes (controls) who were a mean age of 14.7 years and most (92%) were White. The girls with and without diabetes had similar rates of previous fractures (44% and 51%).

Those with diabetes had been diagnosed at a mean age of 9 years and had had diabetes for a mean of 4.6 years.

Researchers calculated participants’ total BPAQ scores based on type, duration, and frequency of bone-loading activities. 

Participants had dual-energy X-ray absorptiometry scans to determine areal bone mineral density (BMD) at the total hip, femoral neck, lumbar spine, and whole body less head.

They also had high-resolution peripheral quantitative computed tomography at the distal tibia and radius to determine volumetric BMD, bone microarchitecture, and estimated bone strength (calculated using microfinite element analysis).

The two groups had similar total BPAQ scores (57.3 and 64.6), with a median score of 49.

BPAQ scores were positively associated with areal BMD at all sites (whole body, lumbar spine, total hip, femoral neck, and 1/3 radius) and with trabecular BMD and estimated failure load at the distal radius and tibia (P < .05 for all, adjusted for bone age).

Among participants with low physical activity (BPAQ below the median), compared with controls, those with type 1 diabetes had 6.6% lower aerial BMD at the lumbar spine (0.868 vs. 0.929 g/cm³; P = .04), 8% lower trabecular volumetric BMD at the distal radius (128.5 vs. 156.8 mg/cm³; P = .01), and 12% lower estimated failure load. Results at the distal tibia were similar.
 

Next steps

“More observational studies in males and females across a broader age spectrum would be helpful,” Dr. Bachrach noted. “The ‘gold standard’ model would be a long-term randomized controlled activity intervention study.”

“Further studies are underway [in girls and boys] using objective measures of activity including accelerometry and longitudinal observation to help confirm the findings from the current study,” Dr. Bouxsein said. “Ultimately, trials of activity interventions in children with [type 1 diabetes] will be the gold standard to determine to what extent physical activity can mitigate bone disease in [type 1 diabetes],” she agreed.

The study authors and Dr. Bachrach have reported no relevant financial relationships.

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

In a small cross-sectional study of 10- to 16-year-old girls with and without type 1 diabetes, both groups were equally physically active, based on their replies to the bone-specific physical activity questionnaire (BPAQ).

However, among the more sedentary girls (with BPAQ scores below the median), those with type 1 diabetes had worse markers of bone health in imaging tests compared with the girls without diabetes.

“The deleterious effect of [type 1 diabetes] on bone health in girls is most pronounced in those with less weight-bearing activity,” the researchers summarize in a poster presented at the annual meeting of the American Society of Bone and Mineral Research.

However, this is early research and further study is needed, the group cautions.

“Ongoing studies with objective measures of physical activity as well as interventional studies will clarify whether increasing physical activity may improve bone health and reduce fracture risk in this vulnerable group,” they conclude.

“If you look at the sedentary kids, there’s a big discrepancy between the kids who have diabetes and the control kids, and that’s if we’re looking at radius or tibia or trabecular bone density or estimated failure load,” senior author Deborah M. Mitchell, MD, said in an interview at the poster session.

However, “when we look at the kids who are more physically active, we’re really not seeing as much difference [in bone health] between the kids with and without diabetes,” said Dr. Mitchell, a pediatric endocrinologist at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

But she also acknowledged, “There’s all sorts of caveats, including that this is retrospective questionnaire data.”

However, if further, rigorous studies confirm these findings, “physical activity is potentially a really effective means of improving bone quality in kids with type 1 diabetes.”

“This study suggests that bone-loading physical activity can substantially improve skeletal health in children with [type 1 diabetes] and should provide hope for patients and their families that they can take some action to prevent or mitigate the effects of diabetes on bone,” coauthor and incoming ASBMR President Mary L. Bouxsein, PhD, told this news organization in an email.

“We interpret these data as an important reason to advocate for increased time in moderate to vigorous bone-loading activity,” said Dr. Bouxsein, professor, department of orthopedic surgery, Harvard Medical School, Boston, “though the ‘dose’ in terms of hours per day or episodes per week to promote optimal bone health is still to be determined.”
 

“Ongoing debate,” “need stronger proof”

Asked for comment, Laura K. Bachrach, MD, who was not involved with the research, noted: “Activity benefits the development of bone strength through effects on bone geometry more than ‘density,’ and conversely, lack of physical activity can compromise gains in cortical bone diameter and thickness.”

However, “there is ongoing debate about the impact of type 1 diabetes on bone health and the factor(s) determining risk,” Dr. Bachrach, a pediatric endocrinologist at Stanford Children’s Health, Palo Alto, Calif., told this news organization in an email.  

The current findings suggest “that physical activity in adolescent girls provided protection against potential adverse effects of type 1 diabetes,” said Dr. Bachrach, who spoke about bone fragility in childhood in a video commentary in 2021.

Study strengths, she noted, “include the rigor and expertise of the investigators, use of multiple surrogate measures that capture bone geometry/microarchitecture, as well as the inclusion of healthy local controls.”  

“The study is limited by the cross-sectional design and subjects who opted, or not, to be active,” she added. “Stronger proof of the protective effects of activity on bone health in type 1 diabetes would require a randomized longitudinal intervention study, as alluded to by the authors of the study.”
 

Hypothesis: Those with type 1 diabetes acquire less bone mass in early 20s

The excess fracture risk in children with type 1 diabetes has been previously reported and is 14%-35% higher than the fracture risk in children without diabetes, Dr. Bouxsein explained. And “between 30% to 50% of kids [with type 1 diabetes] will have a fracture before the age of 18, so the excess fracture risk in diabetes is not clinically obvious,” she added.

However, “several lines of evidence strongly suggest that bone mass and microarchitecture at the time of peak bone mass (early 20s) is a major determinant of fracture risk throughout the lifespan,” she noted.

“Our hypothesis,” Dr. Bouxsein said, “is that the metabolic disruptions of diabetes, when they are present during the acquisition of peak bone mass, interfere with optimal bone development, and therefore may contribute to increased fracture risk later in life.”

Dr. Bachrach agreed that “peak bone strength is achieved by early adulthood, making childhood and adolescence important times to optimize bone health,” and that “peak bone strength is a predictor of lifetime risk of osteoporosis.”

“The diagnosis of pediatric osteoporosis is made when a child or teen sustains a vertebral fracture or femur fracture with minimal or no trauma,” she explained. “The diagnosis can also be made in a pediatric patient with low BMD [bone mineral density] for age in combination with a history of several long-bone fractures.”

Dr. Mitchell noted that type 1 diabetes is associated with a higher risk of fractures, which is sixfold in adults. In another study, she said, the group showed that in 10- to 16-year-old girls who’ve only had diabetes for a few years, “trabecular bone density is lower, they have lower estimated failure load, and longitudinally when we follow them, at least at the radius, we’re seeing bone loss at a relatively young age when we wouldn’t be expecting to see bone loss.”
 

80 girls enrolled, half had type 1 diabetes

Researchers enrolled 36 girls with type 1 diabetes and 44 girls without type 1 diabetes (controls) who were a mean age of 14.7 years and most (92%) were White. The girls with and without diabetes had similar rates of previous fractures (44% and 51%).

Those with diabetes had been diagnosed at a mean age of 9 years and had had diabetes for a mean of 4.6 years.

Researchers calculated participants’ total BPAQ scores based on type, duration, and frequency of bone-loading activities. 

Participants had dual-energy X-ray absorptiometry scans to determine areal bone mineral density (BMD) at the total hip, femoral neck, lumbar spine, and whole body less head.

They also had high-resolution peripheral quantitative computed tomography at the distal tibia and radius to determine volumetric BMD, bone microarchitecture, and estimated bone strength (calculated using microfinite element analysis).

The two groups had similar total BPAQ scores (57.3 and 64.6), with a median score of 49.

BPAQ scores were positively associated with areal BMD at all sites (whole body, lumbar spine, total hip, femoral neck, and 1/3 radius) and with trabecular BMD and estimated failure load at the distal radius and tibia (P < .05 for all, adjusted for bone age).

Among participants with low physical activity (BPAQ below the median), compared with controls, those with type 1 diabetes had 6.6% lower aerial BMD at the lumbar spine (0.868 vs. 0.929 g/cm³; P = .04), 8% lower trabecular volumetric BMD at the distal radius (128.5 vs. 156.8 mg/cm³; P = .01), and 12% lower estimated failure load. Results at the distal tibia were similar.
 

Next steps

“More observational studies in males and females across a broader age spectrum would be helpful,” Dr. Bachrach noted. “The ‘gold standard’ model would be a long-term randomized controlled activity intervention study.”

“Further studies are underway [in girls and boys] using objective measures of activity including accelerometry and longitudinal observation to help confirm the findings from the current study,” Dr. Bouxsein said. “Ultimately, trials of activity interventions in children with [type 1 diabetes] will be the gold standard to determine to what extent physical activity can mitigate bone disease in [type 1 diabetes],” she agreed.

The study authors and Dr. Bachrach have reported no relevant financial relationships.

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

In a small cross-sectional study of 10- to 16-year-old girls with and without type 1 diabetes, both groups were equally physically active, based on their replies to the bone-specific physical activity questionnaire (BPAQ).

However, among the more sedentary girls (with BPAQ scores below the median), those with type 1 diabetes had worse markers of bone health in imaging tests compared with the girls without diabetes.

“The deleterious effect of [type 1 diabetes] on bone health in girls is most pronounced in those with less weight-bearing activity,” the researchers summarize in a poster presented at the annual meeting of the American Society of Bone and Mineral Research.

However, this is early research and further study is needed, the group cautions.

“Ongoing studies with objective measures of physical activity as well as interventional studies will clarify whether increasing physical activity may improve bone health and reduce fracture risk in this vulnerable group,” they conclude.

“If you look at the sedentary kids, there’s a big discrepancy between the kids who have diabetes and the control kids, and that’s if we’re looking at radius or tibia or trabecular bone density or estimated failure load,” senior author Deborah M. Mitchell, MD, said in an interview at the poster session.

However, “when we look at the kids who are more physically active, we’re really not seeing as much difference [in bone health] between the kids with and without diabetes,” said Dr. Mitchell, a pediatric endocrinologist at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

But she also acknowledged, “There’s all sorts of caveats, including that this is retrospective questionnaire data.”

However, if further, rigorous studies confirm these findings, “physical activity is potentially a really effective means of improving bone quality in kids with type 1 diabetes.”

“This study suggests that bone-loading physical activity can substantially improve skeletal health in children with [type 1 diabetes] and should provide hope for patients and their families that they can take some action to prevent or mitigate the effects of diabetes on bone,” coauthor and incoming ASBMR President Mary L. Bouxsein, PhD, told this news organization in an email.

“We interpret these data as an important reason to advocate for increased time in moderate to vigorous bone-loading activity,” said Dr. Bouxsein, professor, department of orthopedic surgery, Harvard Medical School, Boston, “though the ‘dose’ in terms of hours per day or episodes per week to promote optimal bone health is still to be determined.”
 

“Ongoing debate,” “need stronger proof”

Asked for comment, Laura K. Bachrach, MD, who was not involved with the research, noted: “Activity benefits the development of bone strength through effects on bone geometry more than ‘density,’ and conversely, lack of physical activity can compromise gains in cortical bone diameter and thickness.”

However, “there is ongoing debate about the impact of type 1 diabetes on bone health and the factor(s) determining risk,” Dr. Bachrach, a pediatric endocrinologist at Stanford Children’s Health, Palo Alto, Calif., told this news organization in an email.  

The current findings suggest “that physical activity in adolescent girls provided protection against potential adverse effects of type 1 diabetes,” said Dr. Bachrach, who spoke about bone fragility in childhood in a video commentary in 2021.

Study strengths, she noted, “include the rigor and expertise of the investigators, use of multiple surrogate measures that capture bone geometry/microarchitecture, as well as the inclusion of healthy local controls.”  

“The study is limited by the cross-sectional design and subjects who opted, or not, to be active,” she added. “Stronger proof of the protective effects of activity on bone health in type 1 diabetes would require a randomized longitudinal intervention study, as alluded to by the authors of the study.”
 

Hypothesis: Those with type 1 diabetes acquire less bone mass in early 20s

The excess fracture risk in children with type 1 diabetes has been previously reported and is 14%-35% higher than the fracture risk in children without diabetes, Dr. Bouxsein explained. And “between 30% to 50% of kids [with type 1 diabetes] will have a fracture before the age of 18, so the excess fracture risk in diabetes is not clinically obvious,” she added.

However, “several lines of evidence strongly suggest that bone mass and microarchitecture at the time of peak bone mass (early 20s) is a major determinant of fracture risk throughout the lifespan,” she noted.

“Our hypothesis,” Dr. Bouxsein said, “is that the metabolic disruptions of diabetes, when they are present during the acquisition of peak bone mass, interfere with optimal bone development, and therefore may contribute to increased fracture risk later in life.”

Dr. Bachrach agreed that “peak bone strength is achieved by early adulthood, making childhood and adolescence important times to optimize bone health,” and that “peak bone strength is a predictor of lifetime risk of osteoporosis.”

“The diagnosis of pediatric osteoporosis is made when a child or teen sustains a vertebral fracture or femur fracture with minimal or no trauma,” she explained. “The diagnosis can also be made in a pediatric patient with low BMD [bone mineral density] for age in combination with a history of several long-bone fractures.”

Dr. Mitchell noted that type 1 diabetes is associated with a higher risk of fractures, which is sixfold in adults. In another study, she said, the group showed that in 10- to 16-year-old girls who’ve only had diabetes for a few years, “trabecular bone density is lower, they have lower estimated failure load, and longitudinally when we follow them, at least at the radius, we’re seeing bone loss at a relatively young age when we wouldn’t be expecting to see bone loss.”
 

80 girls enrolled, half had type 1 diabetes

Researchers enrolled 36 girls with type 1 diabetes and 44 girls without type 1 diabetes (controls) who were a mean age of 14.7 years and most (92%) were White. The girls with and without diabetes had similar rates of previous fractures (44% and 51%).

Those with diabetes had been diagnosed at a mean age of 9 years and had had diabetes for a mean of 4.6 years.

Researchers calculated participants’ total BPAQ scores based on type, duration, and frequency of bone-loading activities. 

Participants had dual-energy X-ray absorptiometry scans to determine areal bone mineral density (BMD) at the total hip, femoral neck, lumbar spine, and whole body less head.

They also had high-resolution peripheral quantitative computed tomography at the distal tibia and radius to determine volumetric BMD, bone microarchitecture, and estimated bone strength (calculated using microfinite element analysis).

The two groups had similar total BPAQ scores (57.3 and 64.6), with a median score of 49.

BPAQ scores were positively associated with areal BMD at all sites (whole body, lumbar spine, total hip, femoral neck, and 1/3 radius) and with trabecular BMD and estimated failure load at the distal radius and tibia (P < .05 for all, adjusted for bone age).

Among participants with low physical activity (BPAQ below the median), compared with controls, those with type 1 diabetes had 6.6% lower aerial BMD at the lumbar spine (0.868 vs. 0.929 g/cm³; P = .04), 8% lower trabecular volumetric BMD at the distal radius (128.5 vs. 156.8 mg/cm³; P = .01), and 12% lower estimated failure load. Results at the distal tibia were similar.
 

Next steps

“More observational studies in males and females across a broader age spectrum would be helpful,” Dr. Bachrach noted. “The ‘gold standard’ model would be a long-term randomized controlled activity intervention study.”

“Further studies are underway [in girls and boys] using objective measures of activity including accelerometry and longitudinal observation to help confirm the findings from the current study,” Dr. Bouxsein said. “Ultimately, trials of activity interventions in children with [type 1 diabetes] will be the gold standard to determine to what extent physical activity can mitigate bone disease in [type 1 diabetes],” she agreed.

The study authors and Dr. Bachrach have reported no relevant financial relationships.

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

STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.

“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.

baibaz/iStock/Getty Images

She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.

The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.

Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.

“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.

The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.

Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”

And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.

“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
 

Red meat damages, dairy protects

The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.

Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).

The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).

Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.

And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.

Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
 

What are the mechanisms?

The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.

In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”

Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”

Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”

And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.

What about vegan diets? The devil is in the details

Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”

“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”

Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.

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

STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.

“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.

baibaz/iStock/Getty Images

She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.

The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.

Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.

“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.

The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.

Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”

And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.

“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
 

Red meat damages, dairy protects

The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.

Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).

The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).

Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.

And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.

Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
 

What are the mechanisms?

The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.

In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”

Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”

Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”

And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.

What about vegan diets? The devil is in the details

Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”

“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”

Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.

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

STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.

“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.

baibaz/iStock/Getty Images

She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.

The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.

Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.

“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.

The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.

Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”

And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.

“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
 

Red meat damages, dairy protects

The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.

Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).

The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).

Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.

And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.

Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
 

What are the mechanisms?

The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.

In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”

Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”

Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”

And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.

What about vegan diets? The devil is in the details

Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”

“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”

Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.

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

Patients with iron overload – serum ferritin greater than 1,000 mcg/L or a diagnosis of hemochromatosis or thalassemia – were 60% more likely to have an osteoporotic fracture during an up to 10-year follow-up than matched control patients, in a large study.

Compared with control patients, those with iron overload had a roughly twofold increased risk of a vertebral fracture, as well as an increased risk of a hip or humerus fracture, but not a forearm fracture.

The increased risk of fracture in men with iron overload (compared with other matched men) was greater than the increased risk of fracture in women with iron overload (compared with other matched women).

Andrea Burden, PhD, presented the findings during a late-breaking clinical science session at the annual meeting of the American Society of Bone and Mineral Research.
 

‘We should worry about the bones as well as the liver’

Based on these results, clinicians should probably do earlier bone mineral density (BMD) determinations to screen for osteoporosis and perhaps consider prophylaxis with vitamin D and calcium, said Dr. Burden, assistant professor, Institute of Pharmaceutical Sciences, ETH Zürich.

“However, I say that with a bunch of caution,” she added, “because we actually don’t have much evidence of the impact of these treatment differences on fracture risk.”

“This is the first large population study on this topic,” although there have been a few case reports, Dr. Burden explained in an interview.

However, “the high iron overload of greater than 1,000 mcg/L is not common, and hereditary hemochromatosis or thalassemia also are very rare,” she noted.

“The study shows that, once patients have an iron overload of more than 1,000 mcg/L, we need to be doing regular checks for their BMD and figuring how to best minimize their fracture risk,” she said.

“A twofold risk for a vertebral fracture” in patients with iron overload “is really high,” she noted. It is known that men with iron overload have loss of testosterone, but it may be less well known that they have an increased fracture risk.

“We worry about the liver,” she said, “not so much about the bones, and this shows us that we really should.”

Session comoderator Michael J. Econs, MD, who was not involved with the research, agreed. “Iron overload does occur, and it is a clinically important problem and can lead to hemochromatosis, which can lead to a whole host of diseases, but the most common is liver disease,” he told this news organization.

“So, it is a clinically important problem, not only in people who are genetically predisposed but in people who get frequent transfusion,” said Dr. Econs, distinguished professor of medicine and medical and molecular genetics at Indiana University, Indianapolis.

Now this new study has found an increase in fractures in such people, he noted.
 

Large case-control study used U.K. database

Using data from the IQVIA Medical Research Database, researchers identified 21,166 iron overload patients aged 18 years and older who saw a general practitioner in the United Kingdom between 2010 and 2020 and had a serum ferritin level above 1,000 mcg/L or a diagnostic code for hemochromatosis or nonanemic thalassemia.

They matched each iron overload patient with up to 10 control patients based on age, sex, year, and general practitioner, for a total of 198,037 control patients.

Patients were a mean age of 59 years and 59% were men.

During follow-up there were 777 fractures in the iron-overload patients (9.61 fractures per 1,000 patient-years) and 4,344 fractures in the control group (4.68 fractures per 1,000 patient-years).

In adjusted hazard ratio models, researchers adjusted for age, sex, body mass index, alcohol, smoking, history of fractures earlier than 365 days prior to study entry, hypogonadism, osteoporosis, medications, and comorbidities.

Overall, patients in the iron overload group had a 60% higher risk of an osteoporotic fracture (aHR, 1.60).

Among women, the incidence of osteoporotic fracture was 12.63 per 1,000 patient-years in the iron overload group and 7.09 per 1,000 patient-years in the control group.

Women with iron overload had a 48% higher risk of osteoporotic fracture, compared with other women (aHR, 1.48).

Among men, the incidence of osteoporotic fracture was 6.71 per 1,000 patient-years in the iron overload group and 3.01 per 1,000 patient-years in the control group.

Men with iron overload therefore had an 82% higher risk of osteoporotic fracture, compared with other men (aHR, 1.82).

Compared with patients without iron overload, patients with iron overload had an increased risk of a vertebral (aHR, 2.18), hip (aHR, 1.60), and humerus (aHR, 1.82) fracture but not a forearm fracture.

The researchers acknowledge that study limitations include they did not look at phlebotomy or changes in ferritin levels, and they excluded patients with hereditary hemochromatosis diagnosed before age 18.

The work was funded by the German Research Foundation. One of the researchers has reported receiving an independent grant from Pharmacosmos. The other researchers as well as Dr. Econs have reported no relevant financial relationships.

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

Patients with iron overload – serum ferritin greater than 1,000 mcg/L or a diagnosis of hemochromatosis or thalassemia – were 60% more likely to have an osteoporotic fracture during an up to 10-year follow-up than matched control patients, in a large study.

Compared with control patients, those with iron overload had a roughly twofold increased risk of a vertebral fracture, as well as an increased risk of a hip or humerus fracture, but not a forearm fracture.

The increased risk of fracture in men with iron overload (compared with other matched men) was greater than the increased risk of fracture in women with iron overload (compared with other matched women).

Andrea Burden, PhD, presented the findings during a late-breaking clinical science session at the annual meeting of the American Society of Bone and Mineral Research.
 

‘We should worry about the bones as well as the liver’

Based on these results, clinicians should probably do earlier bone mineral density (BMD) determinations to screen for osteoporosis and perhaps consider prophylaxis with vitamin D and calcium, said Dr. Burden, assistant professor, Institute of Pharmaceutical Sciences, ETH Zürich.

“However, I say that with a bunch of caution,” she added, “because we actually don’t have much evidence of the impact of these treatment differences on fracture risk.”

“This is the first large population study on this topic,” although there have been a few case reports, Dr. Burden explained in an interview.

However, “the high iron overload of greater than 1,000 mcg/L is not common, and hereditary hemochromatosis or thalassemia also are very rare,” she noted.

“The study shows that, once patients have an iron overload of more than 1,000 mcg/L, we need to be doing regular checks for their BMD and figuring how to best minimize their fracture risk,” she said.

“A twofold risk for a vertebral fracture” in patients with iron overload “is really high,” she noted. It is known that men with iron overload have loss of testosterone, but it may be less well known that they have an increased fracture risk.

“We worry about the liver,” she said, “not so much about the bones, and this shows us that we really should.”

Session comoderator Michael J. Econs, MD, who was not involved with the research, agreed. “Iron overload does occur, and it is a clinically important problem and can lead to hemochromatosis, which can lead to a whole host of diseases, but the most common is liver disease,” he told this news organization.

“So, it is a clinically important problem, not only in people who are genetically predisposed but in people who get frequent transfusion,” said Dr. Econs, distinguished professor of medicine and medical and molecular genetics at Indiana University, Indianapolis.

Now this new study has found an increase in fractures in such people, he noted.
 

Large case-control study used U.K. database

Using data from the IQVIA Medical Research Database, researchers identified 21,166 iron overload patients aged 18 years and older who saw a general practitioner in the United Kingdom between 2010 and 2020 and had a serum ferritin level above 1,000 mcg/L or a diagnostic code for hemochromatosis or nonanemic thalassemia.

They matched each iron overload patient with up to 10 control patients based on age, sex, year, and general practitioner, for a total of 198,037 control patients.

Patients were a mean age of 59 years and 59% were men.

During follow-up there were 777 fractures in the iron-overload patients (9.61 fractures per 1,000 patient-years) and 4,344 fractures in the control group (4.68 fractures per 1,000 patient-years).

In adjusted hazard ratio models, researchers adjusted for age, sex, body mass index, alcohol, smoking, history of fractures earlier than 365 days prior to study entry, hypogonadism, osteoporosis, medications, and comorbidities.

Overall, patients in the iron overload group had a 60% higher risk of an osteoporotic fracture (aHR, 1.60).

Among women, the incidence of osteoporotic fracture was 12.63 per 1,000 patient-years in the iron overload group and 7.09 per 1,000 patient-years in the control group.

Women with iron overload had a 48% higher risk of osteoporotic fracture, compared with other women (aHR, 1.48).

Among men, the incidence of osteoporotic fracture was 6.71 per 1,000 patient-years in the iron overload group and 3.01 per 1,000 patient-years in the control group.

Men with iron overload therefore had an 82% higher risk of osteoporotic fracture, compared with other men (aHR, 1.82).

Compared with patients without iron overload, patients with iron overload had an increased risk of a vertebral (aHR, 2.18), hip (aHR, 1.60), and humerus (aHR, 1.82) fracture but not a forearm fracture.

The researchers acknowledge that study limitations include they did not look at phlebotomy or changes in ferritin levels, and they excluded patients with hereditary hemochromatosis diagnosed before age 18.

The work was funded by the German Research Foundation. One of the researchers has reported receiving an independent grant from Pharmacosmos. The other researchers as well as Dr. Econs have reported no relevant financial relationships.

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

Patients with iron overload – serum ferritin greater than 1,000 mcg/L or a diagnosis of hemochromatosis or thalassemia – were 60% more likely to have an osteoporotic fracture during an up to 10-year follow-up than matched control patients, in a large study.

Compared with control patients, those with iron overload had a roughly twofold increased risk of a vertebral fracture, as well as an increased risk of a hip or humerus fracture, but not a forearm fracture.

The increased risk of fracture in men with iron overload (compared with other matched men) was greater than the increased risk of fracture in women with iron overload (compared with other matched women).

Andrea Burden, PhD, presented the findings during a late-breaking clinical science session at the annual meeting of the American Society of Bone and Mineral Research.
 

‘We should worry about the bones as well as the liver’

Based on these results, clinicians should probably do earlier bone mineral density (BMD) determinations to screen for osteoporosis and perhaps consider prophylaxis with vitamin D and calcium, said Dr. Burden, assistant professor, Institute of Pharmaceutical Sciences, ETH Zürich.

“However, I say that with a bunch of caution,” she added, “because we actually don’t have much evidence of the impact of these treatment differences on fracture risk.”

“This is the first large population study on this topic,” although there have been a few case reports, Dr. Burden explained in an interview.

However, “the high iron overload of greater than 1,000 mcg/L is not common, and hereditary hemochromatosis or thalassemia also are very rare,” she noted.

“The study shows that, once patients have an iron overload of more than 1,000 mcg/L, we need to be doing regular checks for their BMD and figuring how to best minimize their fracture risk,” she said.

“A twofold risk for a vertebral fracture” in patients with iron overload “is really high,” she noted. It is known that men with iron overload have loss of testosterone, but it may be less well known that they have an increased fracture risk.

“We worry about the liver,” she said, “not so much about the bones, and this shows us that we really should.”

Session comoderator Michael J. Econs, MD, who was not involved with the research, agreed. “Iron overload does occur, and it is a clinically important problem and can lead to hemochromatosis, which can lead to a whole host of diseases, but the most common is liver disease,” he told this news organization.

“So, it is a clinically important problem, not only in people who are genetically predisposed but in people who get frequent transfusion,” said Dr. Econs, distinguished professor of medicine and medical and molecular genetics at Indiana University, Indianapolis.

Now this new study has found an increase in fractures in such people, he noted.
 

Large case-control study used U.K. database

Using data from the IQVIA Medical Research Database, researchers identified 21,166 iron overload patients aged 18 years and older who saw a general practitioner in the United Kingdom between 2010 and 2020 and had a serum ferritin level above 1,000 mcg/L or a diagnostic code for hemochromatosis or nonanemic thalassemia.

They matched each iron overload patient with up to 10 control patients based on age, sex, year, and general practitioner, for a total of 198,037 control patients.

Patients were a mean age of 59 years and 59% were men.

During follow-up there were 777 fractures in the iron-overload patients (9.61 fractures per 1,000 patient-years) and 4,344 fractures in the control group (4.68 fractures per 1,000 patient-years).

In adjusted hazard ratio models, researchers adjusted for age, sex, body mass index, alcohol, smoking, history of fractures earlier than 365 days prior to study entry, hypogonadism, osteoporosis, medications, and comorbidities.

Overall, patients in the iron overload group had a 60% higher risk of an osteoporotic fracture (aHR, 1.60).

Among women, the incidence of osteoporotic fracture was 12.63 per 1,000 patient-years in the iron overload group and 7.09 per 1,000 patient-years in the control group.

Women with iron overload had a 48% higher risk of osteoporotic fracture, compared with other women (aHR, 1.48).

Among men, the incidence of osteoporotic fracture was 6.71 per 1,000 patient-years in the iron overload group and 3.01 per 1,000 patient-years in the control group.

Men with iron overload therefore had an 82% higher risk of osteoporotic fracture, compared with other men (aHR, 1.82).

Compared with patients without iron overload, patients with iron overload had an increased risk of a vertebral (aHR, 2.18), hip (aHR, 1.60), and humerus (aHR, 1.82) fracture but not a forearm fracture.

The researchers acknowledge that study limitations include they did not look at phlebotomy or changes in ferritin levels, and they excluded patients with hereditary hemochromatosis diagnosed before age 18.

The work was funded by the German Research Foundation. One of the researchers has reported receiving an independent grant from Pharmacosmos. The other researchers as well as Dr. Econs have reported no relevant financial relationships.

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

Children born after frozen-thawed embryo transfer (FET) may have a higher risk of cancer than children born through fresh embryo transfer or spontaneous conception, a large registry study suggests.

The results, however, “should be interpreted cautiously,” the authors noted, given the low number of cancer cases reported among children born using FET.

Still, the findings do “raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications,” the authors concluded.

The study was published online in PLOS Medicine.

The number of children born after FET has increased globally and even exceeds the number of those born after fresh embryo transfer in many countries. In the United States, for instance, the FET rate has doubled since 2015; FETs constituted almost 80% of all embryo transfers using assisted reproductive technology (ART) without a donor in 2019.

Despite the benefits associated with FET, which include improved embryo survival and higher live birth rates, some previous research has hinted at a higher risk of childhood cancer in this population.

In the current study, researchers from the University of Gothenburg, Sweden, wanted to better understand the risk of childhood cancer following FET. The investigators analyzed data from 171,774 children born via ART, including 22,630 born after FET, as well as roughly 7.7 million children born after spontaneous conception in Denmark, Finland, Norway, and Sweden.

After a mean follow-up of about 10 years, the incidence rate of cancer diagnosed before age 18 years was 16.7 per 100,000 person-years for children born after spontaneous conception (16,184 cases) and 19.3 per 100,000 person-years for children born after ART (329 cases).

The researchers found no increased risk of cancer before age 18 years in the group of children conceived via ART compared with those conceived spontaneously.

However, children born after FET had a significantly higher risk of cancer compared with children born after fresh embryo transfer (adjusted hazard ratio [aHR], 1.59) and spontaneous conception (aHR, 1.65). Specifically with regard to ART, the incidence rate for those born after FET was 30.1 per 100,000 person-years – 48 total cases – compared with 18.8 per 1000,000 person-years after fresh embryo transfer.

Adjustment for macrosomia, birth weight, or major birth defects influenced the association only marginally.

For specific cancer types, children born after FET had more than a twofold higher risk for leukemia in comparison with those born after fresh embryo transfer (aHR, 2.25) and spontaneous conception (aHR, 2.22).

Still, the authors said these results should be interpreted “cautiously,” given the small number of children diagnosed with cancer after FET. The researchers also acknowledged that they do not know why children born after FET would face a higher risk of cancer.

These findings, however, do align with those from a 2019 Dutch population-based study. In the Dutch study, which included more than 24,000 ART-conceived children and more than 23,000 naturally conceived children, the risk of cancer after ART was not higher overall, but it was greater when only those conceived after FET were considered (aHR 1.80); this increased risk, however, was not statistically significant.

“Since the use of FET is substantially increasing, it is important to tease out whether the increased cancer risk is a true risk increase due to the ART procedures using FET, or due to chance or confounding by other factors,” authors of the 2019 Dutch study, Mandy Spaan, PhD, and Flora E. van Leeuwen, PhD, said in an interview.

“But, as childhood cancer is (fortunately) a rare disease, it is very difficult to study this research question among ART children due to limited numbers,” said Dr. Spaan and Dr. van Leeuwen, who are with the Netherlands Cancer Institute.

Given this, the two experts call for additional large population-based cohort studies to investigate the risk of cancer after ART, especially FET, and for a subsequent analysis that pools these data. They hope this strategy “will lead to reliable estimates” and provide information on the risks of FET in comparison with approaches that involve fresh embryos.

The current study had no commercial funding. The study authors as well as Dr. Spaan and Dr. van Leeuwen have disclosed no relevant financial relationships.

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

Children born after frozen-thawed embryo transfer (FET) may have a higher risk of cancer than children born through fresh embryo transfer or spontaneous conception, a large registry study suggests.

The results, however, “should be interpreted cautiously,” the authors noted, given the low number of cancer cases reported among children born using FET.

Still, the findings do “raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications,” the authors concluded.

The study was published online in PLOS Medicine.

The number of children born after FET has increased globally and even exceeds the number of those born after fresh embryo transfer in many countries. In the United States, for instance, the FET rate has doubled since 2015; FETs constituted almost 80% of all embryo transfers using assisted reproductive technology (ART) without a donor in 2019.

Despite the benefits associated with FET, which include improved embryo survival and higher live birth rates, some previous research has hinted at a higher risk of childhood cancer in this population.

In the current study, researchers from the University of Gothenburg, Sweden, wanted to better understand the risk of childhood cancer following FET. The investigators analyzed data from 171,774 children born via ART, including 22,630 born after FET, as well as roughly 7.7 million children born after spontaneous conception in Denmark, Finland, Norway, and Sweden.

After a mean follow-up of about 10 years, the incidence rate of cancer diagnosed before age 18 years was 16.7 per 100,000 person-years for children born after spontaneous conception (16,184 cases) and 19.3 per 100,000 person-years for children born after ART (329 cases).

The researchers found no increased risk of cancer before age 18 years in the group of children conceived via ART compared with those conceived spontaneously.

However, children born after FET had a significantly higher risk of cancer compared with children born after fresh embryo transfer (adjusted hazard ratio [aHR], 1.59) and spontaneous conception (aHR, 1.65). Specifically with regard to ART, the incidence rate for those born after FET was 30.1 per 100,000 person-years – 48 total cases – compared with 18.8 per 1000,000 person-years after fresh embryo transfer.

Adjustment for macrosomia, birth weight, or major birth defects influenced the association only marginally.

For specific cancer types, children born after FET had more than a twofold higher risk for leukemia in comparison with those born after fresh embryo transfer (aHR, 2.25) and spontaneous conception (aHR, 2.22).

Still, the authors said these results should be interpreted “cautiously,” given the small number of children diagnosed with cancer after FET. The researchers also acknowledged that they do not know why children born after FET would face a higher risk of cancer.

These findings, however, do align with those from a 2019 Dutch population-based study. In the Dutch study, which included more than 24,000 ART-conceived children and more than 23,000 naturally conceived children, the risk of cancer after ART was not higher overall, but it was greater when only those conceived after FET were considered (aHR 1.80); this increased risk, however, was not statistically significant.

“Since the use of FET is substantially increasing, it is important to tease out whether the increased cancer risk is a true risk increase due to the ART procedures using FET, or due to chance or confounding by other factors,” authors of the 2019 Dutch study, Mandy Spaan, PhD, and Flora E. van Leeuwen, PhD, said in an interview.

“But, as childhood cancer is (fortunately) a rare disease, it is very difficult to study this research question among ART children due to limited numbers,” said Dr. Spaan and Dr. van Leeuwen, who are with the Netherlands Cancer Institute.

Given this, the two experts call for additional large population-based cohort studies to investigate the risk of cancer after ART, especially FET, and for a subsequent analysis that pools these data. They hope this strategy “will lead to reliable estimates” and provide information on the risks of FET in comparison with approaches that involve fresh embryos.

The current study had no commercial funding. The study authors as well as Dr. Spaan and Dr. van Leeuwen have disclosed no relevant financial relationships.

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

Children born after frozen-thawed embryo transfer (FET) may have a higher risk of cancer than children born through fresh embryo transfer or spontaneous conception, a large registry study suggests.

The results, however, “should be interpreted cautiously,” the authors noted, given the low number of cancer cases reported among children born using FET.

Still, the findings do “raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications,” the authors concluded.

The study was published online in PLOS Medicine.

The number of children born after FET has increased globally and even exceeds the number of those born after fresh embryo transfer in many countries. In the United States, for instance, the FET rate has doubled since 2015; FETs constituted almost 80% of all embryo transfers using assisted reproductive technology (ART) without a donor in 2019.

Despite the benefits associated with FET, which include improved embryo survival and higher live birth rates, some previous research has hinted at a higher risk of childhood cancer in this population.

In the current study, researchers from the University of Gothenburg, Sweden, wanted to better understand the risk of childhood cancer following FET. The investigators analyzed data from 171,774 children born via ART, including 22,630 born after FET, as well as roughly 7.7 million children born after spontaneous conception in Denmark, Finland, Norway, and Sweden.

After a mean follow-up of about 10 years, the incidence rate of cancer diagnosed before age 18 years was 16.7 per 100,000 person-years for children born after spontaneous conception (16,184 cases) and 19.3 per 100,000 person-years for children born after ART (329 cases).

The researchers found no increased risk of cancer before age 18 years in the group of children conceived via ART compared with those conceived spontaneously.

However, children born after FET had a significantly higher risk of cancer compared with children born after fresh embryo transfer (adjusted hazard ratio [aHR], 1.59) and spontaneous conception (aHR, 1.65). Specifically with regard to ART, the incidence rate for those born after FET was 30.1 per 100,000 person-years – 48 total cases – compared with 18.8 per 1000,000 person-years after fresh embryo transfer.

Adjustment for macrosomia, birth weight, or major birth defects influenced the association only marginally.

For specific cancer types, children born after FET had more than a twofold higher risk for leukemia in comparison with those born after fresh embryo transfer (aHR, 2.25) and spontaneous conception (aHR, 2.22).

Still, the authors said these results should be interpreted “cautiously,” given the small number of children diagnosed with cancer after FET. The researchers also acknowledged that they do not know why children born after FET would face a higher risk of cancer.

These findings, however, do align with those from a 2019 Dutch population-based study. In the Dutch study, which included more than 24,000 ART-conceived children and more than 23,000 naturally conceived children, the risk of cancer after ART was not higher overall, but it was greater when only those conceived after FET were considered (aHR 1.80); this increased risk, however, was not statistically significant.

“Since the use of FET is substantially increasing, it is important to tease out whether the increased cancer risk is a true risk increase due to the ART procedures using FET, or due to chance or confounding by other factors,” authors of the 2019 Dutch study, Mandy Spaan, PhD, and Flora E. van Leeuwen, PhD, said in an interview.

“But, as childhood cancer is (fortunately) a rare disease, it is very difficult to study this research question among ART children due to limited numbers,” said Dr. Spaan and Dr. van Leeuwen, who are with the Netherlands Cancer Institute.

Given this, the two experts call for additional large population-based cohort studies to investigate the risk of cancer after ART, especially FET, and for a subsequent analysis that pools these data. They hope this strategy “will lead to reliable estimates” and provide information on the risks of FET in comparison with approaches that involve fresh embryos.

The current study had no commercial funding. The study authors as well as Dr. Spaan and Dr. van Leeuwen have disclosed no relevant financial relationships.

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

STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.

Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.

Lisovskaya/iStock/Getty Images Plus

Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
 

Diet also has role in improving survival in those with type 2 diabetes

Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.

By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.

“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”

She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.

“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”

Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.

The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
 

High versus low intake of various dietary factors

The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.  

Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.

Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).

A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).

Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).

Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.

“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.

She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.  

Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.

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

STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.

Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.

Lisovskaya/iStock/Getty Images Plus

Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
 

Diet also has role in improving survival in those with type 2 diabetes

Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.

By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.

“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”

She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.

“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”

Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.

The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
 

High versus low intake of various dietary factors

The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.  

Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.

Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).

A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).

Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).

Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.

“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.

She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.  

Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.

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

STOCKHOLM – Higher consumption of whole grains, fish, fiber, and omega-3 polyunsaturated fatty acids reduces deaths from all causes in people with type 2 diabetes, show new data.

Results from the systematic review and meta-analysis were presented at the annual meeting of the European Association for the Study of Diabetes by lead author Janett Barbaresko, PhD, a researcher from the German Diabetes Center in Düsseldorf.

Lisovskaya/iStock/Getty Images Plus

Adding just one serving (around 20 g/day) of whole grains from foods such as brown bread, brown rice, or breakfast cereals was associated with about a 16% reduction in all-cause mortality, and each portion of fish consumed per week was associated with a 5% lower risk of all-cause mortality. In addition, eating 5 g/day of fiber was associated with a 14% reduction in all-cause mortality, and 0.1 g/day of omega-3 polyunsaturated fatty acids with a 13% reduction.
 

Diet also has role in improving survival in those with type 2 diabetes

Dr. Barbaresko explained that most dietary recommendations for people with type 2 diabetes are not evidence based or are derived from studies of the general population, and that the degree to which different components of diet are associated with all-cause mortality, or indeed the prevention of morbidity and mortality, remains unknown.

By way of example, she noted the American Diabetes Association 2022 guidelines for the prevention and management of diabetes complications advises limited intake of saturated and trans fatty acids, higher intake of polyunsaturated fatty acids, and following the Mediterranean or DASH (Dietary Approaches to Stop Hypertension) diets.

“Our findings show that dietary factors not only play a role in the prevention of type 2 diabetes, but also seem to be relevant for improving survival in people with diagnosed diabetes,” she said, adding that, “in particular, we found some key aspects of a healthy diet such as higher intakes of whole grains, fiber, fish, and omega-3 polyunsaturated fatty acids may improve survival of individuals with type 2 diabetes.”

She noted that individuals with type 2 diabetes are known to be more prone to circulatory diseases, dementia, cancer, and bone fractures, and that lifestyle modifications, including diet – with or without medications – underpin most management strategies.

“For the first time, we have provided a summary of all published studies on any dietary factor in association to all-cause mortality in individuals with type 2 diabetes,” said Dr. Barbaresko. “Moreover, the certainty of evidence has been evaluated for the first time.”

Matthias Schulze, MD, head of the German Institute of Human Nutrition, Berlin, moderated the session.

The new work “summarizes the available evidence, providing important dietary advice for patients with diabetes, for example, recommending whole grains,” he remarked. “However, the study also points to gaps in knowledge, so for many diet factors, we have either no or few studies, or study quality considered to be low, which calls for more research to fill the gap.”
 

High versus low intake of various dietary factors

The researchers performed meta-analyses based on published studies of all-cause mortality in individuals with type 2 diabetes aged 18 years and over, as associated with dietary patterns, macronutrients (carbohydrates, protein, fat), micronutrients (vitamins and minerals), secondary plant compounds (for example, polyphenols), and supplements.  

Studies were conducted mainly in the United States and Europe with a mean follow-up of 10 years. Low and high intake were compared, and a dose-response relationship between different dietary factors and all-cause mortality was explored to generate summary risk ratios. The researchers also explored how the certainty of evidence was determined.

Decreased mortality from any cause was found for a higher intake of fish (SRR per serving/week, 0.95; over six studies); whole grain (SRR per 20 g/day, 0.84; two studies); fiber (SRR per 5 g/day, 0.86; three studies), and omega-3 polyunsaturated fatty acids (SRR per 0.1 g/day, 0.87; two studies).

A low certainty of evidence was found for an inverse association between all-cause mortality and vegetable consumption (SRR per 100 g/day, 0.88; two studies) and plant protein intake (SRR per 10 g/day, 0.91; three studies).

Eggs were associated with an increased risk of all-cause mortality (SRR per 10 g/day, 1.05; seven studies), as was dietary cholesterol (SRR per 300 mg/day, 1.19; two studies).

Regarding other dietary patterns, including the Mediterranean diet and low-carbohydrate diet, either no association was found and/or the evidence was very uncertain. Likewise, evidence was uncertain for foods including nuts, dairy, meat, sugar and sweets; macronutrients, including carbohydrates; and micronutrients, such as caffeine and vitamin D.

“With the Mediterranean diet, we saw an inverse association [with all-cause mortality] comparing high adherence with low adherence to the Mediterranean diet, but the certainty of evidence was very low, indicating a really uncertain meta-evidence,” remarked Dr. Barbaresko.

She concluded that a greater number of studies is needed to investigate the association of dietary factors with all-cause mortality in type 2 diabetes to strengthen the evidence for several other dietary factors. She also cautioned that meta-analyses are affected by unmeasured and residual confounding.  

Dr. Barbaresko and Dr. Schulze reported no relevant financial relationships.

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

Takeaway

• Early or delayed menopause and a history of irregular menstrual cycles were significantly associated with a greater risk of new-onset atrial fibrillation (AF) in women.
• Women with nulliparity and multiparity had a greater risk of new-onset AF compared with those with one to two live births.

Why this matters

• Findings highlight the significance of considering the reproductive history of women while developing tailored screening and prevention strategies for AF.

Study design

• A population-based cohort study of 235,191 women (age, 40-69 years) without AF and a history of hysterectomy and/or bilateral oophorectomy, identified from the UK Biobank (2006-2010).
• Funding: Gender and Prevention Grant from ZonMw and other.

Key results

• During a median follow-up of 11.6 years, 4,629 (2.0%) women were diagnosed with new-onset AF.
• A history of irregular menstrual cycle was associated with higher risk of new-onset AF (adjusted HR, 1.34; 95% confidence interval, 1.01-1.79; P = .04).
• Compared with women who experienced menarche at the age of 12 years, the risk of new-onset AF was significantly higher in those who experienced menarche:
• –Earlier between the ages of 7 and 11 years (aHR, 1.10; 95% CI, 1.00-1.21; P = .04) and
• –Later between the ages of 13 and 18 years (aHR, 1.08; 95% CI, 1.00-1.17; P = .05).

• The risk of new-onset AF was significantly higher in women who experienced menopause:
• –At the age of < 35 years (aHR, 2.25; 95% CI, 1.48-3.43; P < .001);
• –Between the ages of 35 and 44 years (aHR, 1.24; 95% CI, 1.10-1.39; P < .001); and
• –At the age of ≥ 60 years (aHR, 1.34; 95% CI, 1.10-1.78; P = .04).
• Women with no live births (aHR, 1.13; 95% CI, 1.04-1.24; P < .01), four to six live births (aHR, 1.12; 95% CI, 1.01-1.24; P = .04), and ≥ seven live births (aHR, 1.67; 95% CI, 1.03-2.70; P = .03) vs. those with one to two live births had a significantly higher risk of new-onset AF.

Limitations

• Observational design.

A version of this article first appeared on Medscape UK.

Reference

Lu Z, Aribas E, Geurts S, Roeters van Lennep JE, Ikram MA, Bos MM, de Groot NMS, Kavousi M. Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women. JAMA Netw Open. 2022;5(9):e2229716. doi: 10.1001/jamanetworkopen.2022.29716. PMID: 36048441.

Takeaway

• Early or delayed menopause and a history of irregular menstrual cycles were significantly associated with a greater risk of new-onset atrial fibrillation (AF) in women.
• Women with nulliparity and multiparity had a greater risk of new-onset AF compared with those with one to two live births.

Why this matters

• Findings highlight the significance of considering the reproductive history of women while developing tailored screening and prevention strategies for AF.

Study design

• A population-based cohort study of 235,191 women (age, 40-69 years) without AF and a history of hysterectomy and/or bilateral oophorectomy, identified from the UK Biobank (2006-2010).
• Funding: Gender and Prevention Grant from ZonMw and other.

Key results

• During a median follow-up of 11.6 years, 4,629 (2.0%) women were diagnosed with new-onset AF.
• A history of irregular menstrual cycle was associated with higher risk of new-onset AF (adjusted HR, 1.34; 95% confidence interval, 1.01-1.79; P = .04).
• Compared with women who experienced menarche at the age of 12 years, the risk of new-onset AF was significantly higher in those who experienced menarche:
• –Earlier between the ages of 7 and 11 years (aHR, 1.10; 95% CI, 1.00-1.21; P = .04) and
• –Later between the ages of 13 and 18 years (aHR, 1.08; 95% CI, 1.00-1.17; P = .05).

• The risk of new-onset AF was significantly higher in women who experienced menopause:
• –At the age of < 35 years (aHR, 2.25; 95% CI, 1.48-3.43; P < .001);
• –Between the ages of 35 and 44 years (aHR, 1.24; 95% CI, 1.10-1.39; P < .001); and
• –At the age of ≥ 60 years (aHR, 1.34; 95% CI, 1.10-1.78; P = .04).
• Women with no live births (aHR, 1.13; 95% CI, 1.04-1.24; P < .01), four to six live births (aHR, 1.12; 95% CI, 1.01-1.24; P = .04), and ≥ seven live births (aHR, 1.67; 95% CI, 1.03-2.70; P = .03) vs. those with one to two live births had a significantly higher risk of new-onset AF.

Limitations

• Observational design.

A version of this article first appeared on Medscape UK.

Reference

Lu Z, Aribas E, Geurts S, Roeters van Lennep JE, Ikram MA, Bos MM, de Groot NMS, Kavousi M. Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women. JAMA Netw Open. 2022;5(9):e2229716. doi: 10.1001/jamanetworkopen.2022.29716. PMID: 36048441.

Takeaway

• Early or delayed menopause and a history of irregular menstrual cycles were significantly associated with a greater risk of new-onset atrial fibrillation (AF) in women.
• Women with nulliparity and multiparity had a greater risk of new-onset AF compared with those with one to two live births.

Why this matters

• Findings highlight the significance of considering the reproductive history of women while developing tailored screening and prevention strategies for AF.

Study design

• A population-based cohort study of 235,191 women (age, 40-69 years) without AF and a history of hysterectomy and/or bilateral oophorectomy, identified from the UK Biobank (2006-2010).
• Funding: Gender and Prevention Grant from ZonMw and other.

Key results

• During a median follow-up of 11.6 years, 4,629 (2.0%) women were diagnosed with new-onset AF.
• A history of irregular menstrual cycle was associated with higher risk of new-onset AF (adjusted HR, 1.34; 95% confidence interval, 1.01-1.79; P = .04).
• Compared with women who experienced menarche at the age of 12 years, the risk of new-onset AF was significantly higher in those who experienced menarche:
• –Earlier between the ages of 7 and 11 years (aHR, 1.10; 95% CI, 1.00-1.21; P = .04) and
• –Later between the ages of 13 and 18 years (aHR, 1.08; 95% CI, 1.00-1.17; P = .05).

• The risk of new-onset AF was significantly higher in women who experienced menopause:
• –At the age of < 35 years (aHR, 2.25; 95% CI, 1.48-3.43; P < .001);
• –Between the ages of 35 and 44 years (aHR, 1.24; 95% CI, 1.10-1.39; P < .001); and
• –At the age of ≥ 60 years (aHR, 1.34; 95% CI, 1.10-1.78; P = .04).
• Women with no live births (aHR, 1.13; 95% CI, 1.04-1.24; P < .01), four to six live births (aHR, 1.12; 95% CI, 1.01-1.24; P = .04), and ≥ seven live births (aHR, 1.67; 95% CI, 1.03-2.70; P = .03) vs. those with one to two live births had a significantly higher risk of new-onset AF.

Limitations

• Observational design.

A version of this article first appeared on Medscape UK.

Reference

Lu Z, Aribas E, Geurts S, Roeters van Lennep JE, Ikram MA, Bos MM, de Groot NMS, Kavousi M. Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women. JAMA Netw Open. 2022;5(9):e2229716. doi: 10.1001/jamanetworkopen.2022.29716. PMID: 36048441.

STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.

A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.

MDedge News/Mitchel L. Zoler

Moving away from BMI-centric obesity

“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).

MDedge News/Mitchel L. Zoler

For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.

But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
 

1 standard deviation increase in WHR linked with a 41% increased mortality

The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.

Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.

Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.

One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.

The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.

[email protected]

STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.

A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.

MDedge News/Mitchel L. Zoler

Moving away from BMI-centric obesity

“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).

MDedge News/Mitchel L. Zoler

For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.

But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
 

1 standard deviation increase in WHR linked with a 41% increased mortality

The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.

Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.

Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.

One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.

The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.

[email protected]

STOCKHOLM – New evidence continues to show that alternative measures of adiposity than body mass index, such as waist-to-hip ratio, work better for predicting the risk a person with overweight or obesity faces from their excess weight.

A direct comparison of waist-to-hip ratio (WHR), body mass index (BMI), and fat mass index (FMI) in a total of more than 380,000 United Kingdom residents included in the UK Biobank showed that WHR had the strongest and most consistent relationship to all-cause death, compared with the other two measures, indicating that clinicians should pay more attention to adiposity distribution than they do to BMI when prioritizing obesity interventions, Irfan Khan said at the annual meeting of the European Association for the Study of Diabetes.

MDedge News/Mitchel L. Zoler

Moving away from BMI-centric obesity

“This is a timely topic, because guidelines for treating people with obesity have depended so much on BMI. We want to go from a BMI-centric view to a view of obesity that depends more on disease burden,” commented Matthias Blüher, MD, professor of molecular endocrinology and head of the Obesity Outpatient Clinic for Adults at the University of Leipzig (Germany).

MDedge News/Mitchel L. Zoler

For example, the 2016 obesity management guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology called for a “complications-centric” approach to assessing and intervening in people with obesity rather than a “BMI-centric” approach.

But Dr. Blüher went a step further in an interview, adding that “waist-to-hip ratio is now outdated,” with adjusted measures of WHR such as waist-to-height ratio “considered a better proxy for all-cause death.” He also gave high marks to the Edmonton Obesity Staging System, which independently added to BMI as well as to a diagnosis of metabolic syndrome for predicting mortality in a sample from the U.S. National Health and Nutrition Examination Survey (NHANES). The Edmonton System also surpassed BMI for disease-severity staging using data from more than 23,000 Canadians with a BMI that denoted obesity.
 

1 standard deviation increase in WHR linked with a 41% increased mortality

The study reported by Mr. Khan used both epidemiologic and Mendelian randomization analyses on data collected from more than 380,000 U.K. residents included in the UK Biobank database to examine the statistical associations between BMI, FMI, and WHR and all-cause death. This showed that while BMI and FMI both had significant, independent associations with all-cause mortality, with hazard ratios of 1.14 for each 1 standard deviation increase in BMI and of 1.17 for each standard deviation increase in FMI, the link was a stronger 1.41 per standard deviation increase in WHR, he said.

Another analysis that divided the entire UK Biobank study cohort into 20 roughly similar subgroups by their BMI showed that WHR had the most consistent association across the BMI spectrum.

Further analyses showed that WHR also strongly and significantly linked with cardiovascular disease death and with other causes of death that were not cardiovascular, cancer-related, or associated with respiratory diseases. And the WHR link to all-cause mortality was strongest in men, and much less robust in women, likely because visceral adiposity is much more common among men, even compared with the postmenopausal women who predominate in the UK Biobank cohort.

One more feature of WHR that makes it an attractive metric is its relative ease of measurement, about as easy as BMI, Mr. Khan said.

The study received no commercial funding, and Mr. Khan had no disclosures. Dr. Blüher has been a consultant to or speaker on behalf of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, and Sanofi.

[email protected]

Queen Elizabeth is everywhere. She was even on the last slide of a presentation on COVID, monkeypox, and influenza vaccines given by our physician in charge of quality. This was odd. The presenter wasn’t English. The Queen had nothing to do with vaccines. Nor apparently would she have said even if she did have an opinion about them. But there we were, an audience of physicians and staff pausing for a moment of remembrance of her.

I’m not a Monarchist – except perhaps for the Kennedys. I grew up in New England. I don’t have an opinion on whether or not the British Crown should endure. But I do marvel at the astounding effect Queen Elizabeth’s passing had on so many around the world. Her personal qualities, particularly her steadiness and humane sympathy, might explain why so many are sad hearing the news. But also I think there was something in her role that we all wished for: Not the owning of palaces and sceptres, but rather, the respect that was given to her.

She was a stateswoman of “unmatched dignity,” the White House wrote. That was true, but it seems being the Queen might have been the last job on earth where such dignity is still possible. Certainly in politics, education, and even health care, there doesn’t seem to be much left lately.

The same day of that presentation I walked into the room of a patient 22 minutes late, she held her arm forth tapping her watch to indicate the time and my tardiness. Unnecessary, if not impertinent. Covering for one of my female physician colleagues, I read an email from a patient which began, “Dear Julie, With all due respect …” Another patient submitted a photo for us to review that was clearly taken from her car while waiting at a stop light. Hardly the consideration a clinical encounter should be given.

Much has been lost for patients. too. There are patients trying to make appointments lately who are told: “There are none. Call back later.” Gone it seems are the days of a two-part office visit, the first part fully clothed in the physician’s office, then the exam. There is no dignified way to remove exam paper stuck to your backside before introducing yourself to the doctor. Maybe that last slide of Her Majesty was in fact for us to have a moment of silence for what we’ve all lost.

Walter Bagehot (pronounce it “Baj-et” if you tell this story to your Harlan wine friends) was a political writer and editor of The Economist in the 1860s. He famously said that the secret to the English government was having two kinds of institutions, the dignified and the efficient. The efficient, Parliament, was responsible for all the work. The dignified, the Crown, gives significance and holds everyone’s respect. If medicine ever once was both dignified and efficient, we aren’t lately. We push to reduce backlogs, offer same-time virtual care, work to reduce costs. We’ve driven medicine to the efficient and left little of the dignity it seems.

The Queen will be remembered for her lifelong dedication to the laborious service of others. Even though each of us in medicine pledges the same, we also mourn this week the loss of dignity that once came with it.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Queen Elizabeth is everywhere. She was even on the last slide of a presentation on COVID, monkeypox, and influenza vaccines given by our physician in charge of quality. This was odd. The presenter wasn’t English. The Queen had nothing to do with vaccines. Nor apparently would she have said even if she did have an opinion about them. But there we were, an audience of physicians and staff pausing for a moment of remembrance of her.

I’m not a Monarchist – except perhaps for the Kennedys. I grew up in New England. I don’t have an opinion on whether or not the British Crown should endure. But I do marvel at the astounding effect Queen Elizabeth’s passing had on so many around the world. Her personal qualities, particularly her steadiness and humane sympathy, might explain why so many are sad hearing the news. But also I think there was something in her role that we all wished for: Not the owning of palaces and sceptres, but rather, the respect that was given to her.

She was a stateswoman of “unmatched dignity,” the White House wrote. That was true, but it seems being the Queen might have been the last job on earth where such dignity is still possible. Certainly in politics, education, and even health care, there doesn’t seem to be much left lately.

The same day of that presentation I walked into the room of a patient 22 minutes late, she held her arm forth tapping her watch to indicate the time and my tardiness. Unnecessary, if not impertinent. Covering for one of my female physician colleagues, I read an email from a patient which began, “Dear Julie, With all due respect …” Another patient submitted a photo for us to review that was clearly taken from her car while waiting at a stop light. Hardly the consideration a clinical encounter should be given.

Much has been lost for patients. too. There are patients trying to make appointments lately who are told: “There are none. Call back later.” Gone it seems are the days of a two-part office visit, the first part fully clothed in the physician’s office, then the exam. There is no dignified way to remove exam paper stuck to your backside before introducing yourself to the doctor. Maybe that last slide of Her Majesty was in fact for us to have a moment of silence for what we’ve all lost.

Walter Bagehot (pronounce it “Baj-et” if you tell this story to your Harlan wine friends) was a political writer and editor of The Economist in the 1860s. He famously said that the secret to the English government was having two kinds of institutions, the dignified and the efficient. The efficient, Parliament, was responsible for all the work. The dignified, the Crown, gives significance and holds everyone’s respect. If medicine ever once was both dignified and efficient, we aren’t lately. We push to reduce backlogs, offer same-time virtual care, work to reduce costs. We’ve driven medicine to the efficient and left little of the dignity it seems.

The Queen will be remembered for her lifelong dedication to the laborious service of others. Even though each of us in medicine pledges the same, we also mourn this week the loss of dignity that once came with it.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Queen Elizabeth is everywhere. She was even on the last slide of a presentation on COVID, monkeypox, and influenza vaccines given by our physician in charge of quality. This was odd. The presenter wasn’t English. The Queen had nothing to do with vaccines. Nor apparently would she have said even if she did have an opinion about them. But there we were, an audience of physicians and staff pausing for a moment of remembrance of her.

I’m not a Monarchist – except perhaps for the Kennedys. I grew up in New England. I don’t have an opinion on whether or not the British Crown should endure. But I do marvel at the astounding effect Queen Elizabeth’s passing had on so many around the world. Her personal qualities, particularly her steadiness and humane sympathy, might explain why so many are sad hearing the news. But also I think there was something in her role that we all wished for: Not the owning of palaces and sceptres, but rather, the respect that was given to her.

She was a stateswoman of “unmatched dignity,” the White House wrote. That was true, but it seems being the Queen might have been the last job on earth where such dignity is still possible. Certainly in politics, education, and even health care, there doesn’t seem to be much left lately.

The same day of that presentation I walked into the room of a patient 22 minutes late, she held her arm forth tapping her watch to indicate the time and my tardiness. Unnecessary, if not impertinent. Covering for one of my female physician colleagues, I read an email from a patient which began, “Dear Julie, With all due respect …” Another patient submitted a photo for us to review that was clearly taken from her car while waiting at a stop light. Hardly the consideration a clinical encounter should be given.

Much has been lost for patients. too. There are patients trying to make appointments lately who are told: “There are none. Call back later.” Gone it seems are the days of a two-part office visit, the first part fully clothed in the physician’s office, then the exam. There is no dignified way to remove exam paper stuck to your backside before introducing yourself to the doctor. Maybe that last slide of Her Majesty was in fact for us to have a moment of silence for what we’ve all lost.

Walter Bagehot (pronounce it “Baj-et” if you tell this story to your Harlan wine friends) was a political writer and editor of The Economist in the 1860s. He famously said that the secret to the English government was having two kinds of institutions, the dignified and the efficient. The efficient, Parliament, was responsible for all the work. The dignified, the Crown, gives significance and holds everyone’s respect. If medicine ever once was both dignified and efficient, we aren’t lately. We push to reduce backlogs, offer same-time virtual care, work to reduce costs. We’ve driven medicine to the efficient and left little of the dignity it seems.

The Queen will be remembered for her lifelong dedication to the laborious service of others. Even though each of us in medicine pledges the same, we also mourn this week the loss of dignity that once came with it.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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

Treatment of people with obesity but without diabetes with the glucagon-like peptide-1 (GLP-1) agonist semaglutide (Wegovy) – hailed at its approval in 2021 as a “game changer” for the treatment of obesity – led to beneficial changes in body mass index (BMI), glycemic control, and other clinical measures.

This collectively cut the calculated risk for possible future development of type 2 diabetes in study participants by more than half, based on post-hoc analysis of data from two pivotal trials that compared semaglutide with placebo.

The findings “suggest that semaglutide could help prevent type 2 diabetes in people with overweight or obesity,” said W. Timothy Garvey, MD, in a presentation at the annual meeting of the European Association for the Study of Diabetes.

Asked to comment, Rodolfo J. Galindo, MD, said: “We devote a significant amount of effort to treating people with diabetes but very little effort for diabetes prevention. We hope that further scientific findings showing the benefits of weight loss, as illustrated by [Dr.] Garvey [and colleagues], for diabetes prevention will change the pandemic of adiposity-based chronic disease.”
 

GLP-1 agonists as complication-reducing agents

Finding a link between treatment with semaglutide and a reduced future risk of developing type 2 diabetes is important because it shows that this regimen is not just a BMI-centric approach to treating people with obesity but is also a way to potentially reduce complications of obesity such as diabetes onset, explained Dr. Garvey, a professor and director of the Diabetes Research Center at the University of Alabama at Birmingham.

Recent obesity-management recommendations have focused on interventions aimed at avoiding complications, as in 2016 guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology, he noted.

Having evidence that treatment with a GLP-1 agonist such as semaglutide can reduce the incidence of diabetes in people with obesity might also help convince payers to more uniformly reimburse for this type of obesity intervention, which up to now has commonly faced coverage limitations, especially in the United States, he said in an interview.

Dr. Garvey added that evidence for a reduction in the incidence of cardiovascular disease complications such as myocardial infarction and stroke may need to join diabetes prevention as proven effects from obesity intervention before coverage decisions change.

He cited the SELECT trial, which is testing the hypothesis that semaglutide treatment of people with overweight or obesity can reduce the incidence of cardiovascular events in about 17,500 participants and with expected completion toward the end of 2023.

“A complication-centric approach to management of people with obesity needs prediction tools that allow a focus on prevention strategies for people with obesity who are at increased risk of developing diabetes,” commented Dr. Galindo, an endocrinologist at Emory University, Atlanta, in an interview.
 

Combined analysis of STEP 1 and STEP 4 data

The analysis conducted by Dr. Garvey and colleagues used data from the STEP 1 trial, which compared semaglutide 2.4 mg subcutaneous once weekly with placebo for weight loss in more than 1,500 people predominantly with obesity (about 6% were overweight) and showed that after 68 weeks semaglutide cut the calculated risk of developing type 2 diabetes over the subsequent 10 years from 18% at baseline to 7%, compared with a drop from 18% at baseline to 16% among those who received placebo.

A second, similar analysis of data from people predominantly with obesity in the STEP 4 trial – which treated around 800 people with semaglutide 2.4 mg for 20 weeks and then randomized them to placebo or continued semaglutide treatment – showed that semaglutide treatment cut their calculated 10-year risk for incident type 2 diabetes from 20% at baseline to about 11% after 20 weeks. The risk rebounded in the study participants who then switched from semaglutide to placebo. Among those randomized to remain on semaglutide for a total of 68 weeks, the 10-year risk fell further to 8%.

Dr. Garvey and associates used a validated prognostic formula, the cardiometabolic disease staging (CMDS) tool, they had previously developed and reported to calculate 10-year risk for development of type 2 diabetes based on three unmodifiable factors (age, sex, and race) and five modifiable factors (BMI, blood pressure, glucose level, HDL cholesterol, and triglycerides). They applied the analysis to data from 1,561 of the STEP 1 participants and 766 participants in the STEP 4 study.

“There is no better tool I know of to predict diabetes incidence,” commented Michael A. Nauck, MD, professor and chief of clinical research, diabetes division, St. Josef Hospital, Bochum, Germany.

In his opinion, the CMDS tool is appropriate for estimating the risk of developing incident type 2 diabetes in populations but not in specific individuals.

The new analyses also showed that, in STEP 1, the impact of semaglutide on reducing future risk of developing type 2 diabetes was roughly the same regardless of whether participants entered the study with prediabetes or were normoglycemic at entry.

Blood glucose changes confer the biggest effect

The biggest contributor among the five modifiable components of the CMDS tool for altering the predicted risk for incident diabetes was the reduction in blood glucose produced by semaglutide treatment, which influenced just under half of the change in predicted risk, Dr. Garvey said. The four other modifiable components had roughly similar individual effects on predicted risk, with change in BMI influencing about 15% of the observed effect.

“Our analysis shows that semaglutide treatment is preventing diabetes via several mechanisms. It’s not just a reduction in glucose,” Dr. Garvey said.

Dr. Nauck cautioned, however, that it is hard to judge the efficacy of an intervention like semaglutide for preventing incident diabetes when one of its effects is to dampen down hyperglycemia, the signal indicator of diabetes onset.

Indeed, semaglutide was first approved as a treatment for type 2 diabetes (known as Ozempic, Novo Nordisk) at slightly lower doses than it is approved for obesity. It is also available as an oral agent to treat diabetes (Rybelsus).  

Dr. Nauck also noted that the results from at least one previously reported study had already shown the same relationship between treatment with the GLP-1 agonist liraglutide as an anti-obesity agent (3.0 mg dose daily, known as Saxenda) and a reduced subsequent incidence of type 2 diabetes but using actual clinical outcomes during 3 years of follow-up rather than a calculated projection of diabetes likelihood.

The SCALE Obesity and Prediabetes trial randomized 2,254 people with prediabetes and overweight or obesity to weekly treatment with 3.0 mg of liraglutide or placebo. After 160 weeks on treatment, the cumulative incidence of type 2 diabetes was 2% in those who received liraglutide and 6% among those on placebo, with a significant hazard ratio reduction of 79% in the incidence of diabetes on liraglutide treatment.

The STEP 1 and STEP 4 trials were sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Garvey has reported serving as an advisor without compensation to Novo Nordisk as well as Boehringer Ingelheim, Eli Lilly, Jazz, and Pfizer. He is also a site principal investigator for multicentered clinical trials sponsored by the University of Alabama at Birmingham and funded by Novo Nordisk, Eli Lilly, Epitomee, and Pfizer. Dr .Galindo has reported being a consultant or advisor for Boehringer Ingelheim, Eli Lilly, Pfizer, Sanofi, and Weight Watchers and receiving research funding from Dexcom, Eli Lilly, and Novo Nordisk. Dr. Nauck has reported being an advisor or consultant to Novo Nordisk as well as to Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, MSD, Regor, and ShouTi/Gasherbrum, receiving research funding from MSD, being a member of a data monitoring and safety board for Inventiva, and being a speaker on behalf of Novo Nordisk as well as for Eli Lilly, Menarini/Berlin Chemie, MSD, and Sun Pharmaceuticals.

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