A provider toolkit with clinically relevant resources related to diagnosis and management of central precocious puberty.

CPP Provider Toolkit

A pair of experts in the management of diabetes review the role of insulin therapy and review the approval process for biosimilars, including the FDA's approval of the first interchangeable insulin biosimilar.

Interchangeable Insulin Biosimilars: A Game Changer in Diabetes Management

Podcast hosted by Diana Isaacs, PharmD, and Natalie Bellini, DNP aimed at providing real-world perspective on the latest advances in diabetes management.

An analysis of data from the DIRECT-PLUS trial is providing new insight into the effects of a modified Mediterranean on visceral adipose tissue among participants in the 18-month 

Results of the study, which assessed the effects of a modified Mediterranean diet characterized by an increased level of polyphenols, found that adherence to the Mediterranean diet reduced visceral fat by 7% and adherence to the healthy diet reduced it by 4.5% compared with the control diet, while the green Mediterranean diet stood apart with a mean reduction in visceral fat of 14%.

"A healthy lifestyle is a strong basis for any weight loss program. We learned from the results of our experiment that the quality of food is no less important than the number of calories consumed and the goal today is to understand the mechanisms of various nutrients, for example, positive ones such as the polyphenols, and negative ones such as empty carbohydrates and processed red meat, on the pace of fat cell differentiation and their aggregation in the viscera," said Iris Shai, MD, of Ben-Gurion University of the Negev, Israel and an adjunct professor from the Harvard School of Public Health, 

Led by Shai and a team of colleagues from Ben-Gurion University and Harvard School of Public Health, the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed (DIRECT-PLUS) was launched with the intent of exploring the effects of the green Mediterranean diet, which is a modified version of the Mediterranean diet enriched with an addition 800 mg of daily dietary polyphenols via consumption of 3-4 cups of green tea and 100 grams of duckweed green shake each day.

The trial enrolled 294 participants and randomized them in a 1:1:1 ratio to a healthy diet, a Mediterranean diet, or the green Mediterranean diet. The primary outcome of interest for the trial was difference in visceral adiposity, which was quantified using magnetic resonance imaging (MRI). The cohort had a mean age of 51 years, 88% were men, the mean BMI was 31.2 kg/m2, and 29% had visceral adipose tissue. The trial had a retention rate of 89.8% and 79.3% of participants completed eligible MRIs.

Upon analysis, a similar degree of weight loss was observed with both the Mediterranean and the green Mediterranean diets, with mean body weight reductions of -2.7% and -3.9%, respectively, and mean reductions in waist circumference of -4.7% and -5.7%, respectively. However, a more than doubling in mean reduction of visceral adipose tissue was observed with the green Mediterranean diet (-14.1%) compared to Mediterranean diet (-6.0%) and the healthy diet (-4.2%) (

 for trend <.05), with this effect independent of age, sex, waist circumference, or weight loss. Investigators pointed out increased consumption of green tea, walnuts, and 

, lower red meat intake, higher total plasma polyphenols , and elevated urine 

 polyphenol were significantly related to greater visceral adipose tissue reductions (

"A 14% reduction in visceral fat is a dramatic achievement for making simple changes to your diet and lifestyle. Weight loss is an important goal only if it is accompanied by impressive results in reducing adipose tissue," added Hila Zelicha, RD, PhD, of the Health and Nutrition Innovative International Research Center at Ben-Gurion University of the Negev, in the aforementioned statement.

The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial,”

Articles

Results of the DIRECT-PLUS trial provide clinicians with new insights into the impact of the Mediterranean diet and a modified Mediterranean diet as a method for inducing weight loss. 

"Green" Mediterranean Diet Could Reduce Visceral Adiposity by 14%

Data from a retrospective analysis of emergency department visits in Sweden from a decade-long period suggests random glucose level measurements at admission could serve as a prognostic marker for all-cause mortality and cardiovascular disease among people without diabetes.

Using data from more than 600,000 patients with a mean follow-up of 3.9 years, results of the study demonstrate patients with disturbed blood glucose were at a greater mortality risk, with a hyperglycemia associated with a 2-fold increase in long-term mortality and a more than doubling in risk of cardiovascular events compared to their normoglycemic counterparts.

“The present result from this large observational study confirms earlier short-, and long-term studies but also suggests that a random blood glucose level at admission predicts death and cardiovascular outcome in patients without known diabetes at a long follow-up period,” wrote investigators.

Conducted by a team from Karolinska Institutet and Karolinska University Hospital, the current research endeavor was undertaken as with the intent of exploring whether elevated blood glucose levels could predict cardiovascular disease and all-cause mortality risk in people without a history of diabetes. With this in mind, investigators designed their study as a retrospective cohort study of patient data recorded from 2006-2016 obtained from a group of 7 hospitals in Stockholm and Gothenburg, Sweden.

Using only the first visit emergency department visit for each individual, investigators identified 618,694 patients with a mean follow-up time of 3.9 years for inclusion in their analysis. Based on baseline blood glucose level patients were categorized into four groups: hypoglycemia (less than 3.9 mmol/L), normal glucose tolerance (3.9-7.8 mmol/L), dysglycemia (7.8-11.1 mmol/L), and hyperglycemia (greater than 11.1 mmol/L). Using this as the exposure of interest, investigators used Cox regression to estimate risk of all-cause mortality and cardiovascular outcomes across these groups.

Of the 618,694 patients included in the study, 0.3% had hypoglycemia, 85% had normal glucose tolerance, 13% had dysglycemia, and 2% patients had hyperglycemia. During the follow-up period, a total of 44,532 deaths occurred among the study cohort. Of these 44,532 patient deaths, 11.5% had hypoglycemia, 6.0% had normal glucose tolerance, 12.7% had dysglycemia, and 20.6% patients had hyperglycemia.

When assessing for risk of all-cause mortality, an increased risk was observed for those with hypoglycemia (HR, 2.58 [95% CI, 2.26-2.96]), hyperglycemia (HR, 1.69 [95% CI, 1.63-1.76]) and dysglycemia (HR 1.16 [95% CI, 1.13-1.19]) when compared to their counterparts with normal glucose tolerance. When assessing for risk of cardiovascular disease events, a more than doubling in risk was observed for hyperglycemia (HR, 2.28 [95% CI, 2.13-2.44]) compared to those with normal glucose tolerance.

“This indicates that a random blood glucose in the ED can help identify patients at risk and further controlled studies to improve their outcome should be considered,” investigators concluded.

Admission glucose as a prognostic marker for all‑cause mortality and cardiovascular disease

An analysis of data from patients admitted to emergency departments from 7 hospitals in Sweden provide insight into the potential of blood glucose at admission for use as a biomarker to predict all-cause mortality and cardiovascular risk in patients without a history of diabetes. 

Blood Glucose at Admission Could Serve as Prognostic Marker in Emergency Departments

An analysis of data from nearly 900,000 women is providing clinicians with an overview of the cardiovascular risk associated with concomitant occurrence of a pair of conditions common among expectant mothers in the US and abroad.

Using data from the Ministry of Health and Long-Term Care of Ontario administrative databases, results of the analysis demonstrated concomitant occurrence gestational diabetes and gestational hypertensive disorder was associated with a 2.4-fold increase in risk of incident cardiovascular disease compared to their counterparts with neither condition, which investigators noted was significantly higher than the increase in risk observed for either condition individually.

“This cohort study found that over time, co-occurrence of [Gestational Diabetes] and [Gestational Hypertensive Disorder] was associated with a much greater postpartum CVD risk than the individual conditions. The systematic identification of both [Gestational Hypertensive Disorder] and [Gestational Diabetes] in obstetrical practice offers an opportunity for a more effective CVD prevention among young women of childbearing age.”

Despite advances across medicine, pitfalls in care and maternal morbidity remain persistent issues for health care systems in North America. With this in mind, a team from Johns Hopkins University School of Medicine, Mount Sinai Hospital, and the Institute for Clinical Evaluative Studies in Toronto, Canada sought to further explore the impact of gestational hypertensive disorders and gestational diabetes on subsequent cardiovascular risk. To do so, they designed a population-based cohort study using data from the Ministry of Health and Long-Term Care of Ontario health care administrative databases, which is that provide investigators with information related to 866,295 women in Ontario with a gestational hypertensive disorder and/or gestational diabetes diagnosis, and a live-birth singleton delivery from July 1, 2007-March 31, 2018 for inclusion in their analyses.

Study participants were identified using diagnostic coding. Investigators pointed out women with pregravid diabetes, hypertension, or cardiovascular disease were excluded from the study. The 866,295-person cohort included in final analyses had a mean age of 30 (SD, 5.6) years.

The primary outcome of interest for the investigators analyses was incident cardiovascular disease, which was a composite of myocardial infarction, acute coronary syndrome, stroke, coronary artery bypass grafting, percutaneous coronary intervention, or carotid endarterectomy. Associations were assessed using Cox regression models, with adjustment for relevant cardiometabolic risk factors.

Overall, 4.9% had an isolated gestational hypertensive disorder, 6.1% had isolated gestational diabetes, and 0.6% had both a gestational hypertensive disorder and gestational diabetes. During the follow-up period, which lasted a mean of 12.8 years and included 7.0 million person-years, a total of 1999 cardiovascular disease events were observed among the study cohort, with 867 occurring during the first 5 years postpartum and 1162 events occurring during the period subsequent to the first 5 years post index delivery.

Results of the investigators’ analysis indicated there was no association of co-occurrence of gestational hypertensive disorders and gestational diabetes (aHR, 1.42 [95% CI, 0.78-2.58]) or gestational diabetes alone (aHR, 0.80 [95% CI, 0.60-1.06]) with incident cardiovascular disease in the first 5 years postpartum. However, investigators noted there was an association observed between isolated gestational hypertensive disorders and incident CVD compared with no gestational hypertensive disorders and no gestational diabetes (aHR, 1.90 [95% CI, 1.51-2.35]) during this time period. 

When assessing risk after the initial 5-year period, results suggested isolated gestational hypertensive disorder (aHR, 1.41 [95% CI, 1.12-1.76]) and co-occurrence of gestational hypertensive disorders and gestational diabetes (aHR, 2.43 [95% CI, 1.60-3.67]) were each associated with a higher risk of incident cardiovascular disease compared to no gestational diabetes and no gestational hypertensive disorder. Investigators pointed out no association was observed between isolated gestational diabetes and incident cardiovascular disease.

“In this large population-based cohort study, extended follow-up after delivery found that while [Gestational Hypertensive Disorder] and [Gestational Diabetes] would each be individually associated with a high risk of CVD, women who experienced both [Gestational Hypertensive Disorder] and [Gestational Diabetes] during a pregnancy were ultimately at significantly higher absolute and relative risk of CVD, as compared to those without either of these conditions,” investigators wrote. “Over time, this risk became more pronounced than that observed among women with each of these conditions separately.”

Association of Concomitant Gestational Hypertensive Disorders and Gestational Diabetes With Cardiovascular Disease

An analysis of more than 800k women in Canada provides insight into the apparent increase in risk of incident cardiovascular disease associated with co-occurrence of gestational diabetes and gestational hypertensive disorders in pregnant women. 

Co-Occuring Gestational Diabetes, Hypertension Linked with Doubling of Future Cardiovascular Risk

The last weekend of each month, our editorial team compiles a list of our most popular endocrinology content from the past month for a month in review recap. The November 2022 endocrinology month in review features coverage of the FDA’s approval of teplizumab, new data related to use of GLP-1 receptor agonists, and a trio of stories on topics pertaining to diabetes technology.

The month of November played host to what some suggest is the greatest advance in diabetes management since the discovery of insulin more than 100 years ago. More than 3 years had elapse since the release of phase 2 data detailing the effects of teplizumab, that included the receipt of a Complete Response Letter and being the subject of an FDA Advisory Committee meeting, but on November 17, 2022 the community witnessed the approval of the first agent indicated to delay the onset of type 1 diabetes in pediatric and adult patients. As part of the month in review, we are highlighting our the 

coverage of the approval announcements from the US FDA and Provention Bio, as well as a special edition episode of 

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives 

that provides in-depth insights into what the approval means for the community and the next steps for education and rollout of the agent.

Teplizumab Receives FDA Approval for Delaying Type 1 Diabetes

On November 17, the US FDA announced the approval of teplizumab (Tzield), which is administered through IV infusion once daily for 14 consecutive days, for delaying the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.

Diabetes Dialogue: What Teplizumab Means for Type 1 Diabetes

Diana Isaacs, PharmD, and Natalie Bellini, DNP, break down what the approval of teplizumab means for type 1 diabetes. During the episode, hosts take a deep dive into type 1 diabetes staging and hypothesize around the role of CDCES in educating primary care and other specialties to optimize the potential of teplizumab.

News & Updates in Use of GLP-1 Receptor Agonists

Recently, not a week goes by without clinically impactful data related to GLP-1 receptor agonists being published. The month of November saw a slew of new studies and information surrounding agents within the class in scientific journals and meetings, such as Obesity Week and the Obesity Medicine Association (OMA) annual meeting. For the November month in review, we’re highlighting our coverage of the STEP TEENS trial, which was published in the 

 featuring Lydia Alexander,president-elect of the OMA, discussing the latest updates in obesity management.

STEP TEENS: Semaglutide 2.4 mg (Wegovy) Weight Loss Benefits Translate to Adolescent Populations

Data from the STEP TEENS trial, which assessed the benefits of semaglutide 2.4 mg (Wegovy) in individuals aged 12-18 years with overweight or obesity, indicates use of the GLP-1 receptor agonist was associated with a mean reduction in body weight of 16% during the 68-week trial.

Diabetes Dialogue: Obesity Updates, with Lydia Alexander, MD

In this episode, Diana Isaacs, PharmD, and Natalie Bellini, DNP, are joined by Lydia Alexander, MD, president-elect of the Obesity Medicine Association, to discuss the updates in the landscape of obesity management as well as a deep dive into the recent American Gastroenterological Association guidelines for pharmacological management and the OMA's annual meeting.

The highlights from our editorial coverage related to diabetes technologies for the month of November include a trio of stories that could be described as the Good, the Bad, and the Ugly. The Good: A new study assessing ease of use of the newest generation of the Dexcom CGM system in older people with type 2 diabetes suggests setup of the Dexcom G7 CGM required half as many steps to set up and deploy as the G6 system. The Bad: On November 17, the US FDA issued a Class I Recall, the most serious type of recall, for Insulet Omnipod DASH Insulin Management System PDMs over issues with device batteries, including instances that led to fires. The Ugly: A new study from Johns Hopkins draws attention to racial disparities in prescription and frequency of patient-provider discussions surrounding CGM and insulin pumps, an unfortunate reality that plagues optimal uptake of these devices.

Study Finds Dexcom G7 Setup is Easier, Requires Fewer Tasks for Older Adults than Previous Generations

A formal task analysis conducted in older adults with type 2 diabetes provides insight into the ease of use and task burden associated with uptake of the Dexcom G7 CGM system, with results indicating use of the system required fewer than half as many steps to initiate as previous generations of the CGM system.

FDA Issues Recall for Insulet Devices for Battery, Overheating Issues that Could Cause Fire

Announced on November 17, the US FDA Class I recall for the Insulet Omnipod DASH Insulin Management System Personal Diabetes Manager comes after the company had received more than 450 complaints related to battery swelling, fluid leakage from battery, and extreme overheating, including 3 instances that included fires.

Black Patients Less Likely to be Prescribed, Have Discussions around CGMs, Insulin Pumps


A Johns Hopkins-led analysis provides a snapshot of trends in racial disparities seen in regard to both uptake and engagement in discussions with providers around continuous glucose monitoring and insulin pumps among adults with type 1 diabetes.

The November 2022 endocrine month in review features coverage of the FDA’s approval of teplizumab, new data related to use of GLP-1 receptor agonists, and a trio of stories on topics pertaining to diabetes technology.

Endocrine Month in Review: November 2022

Integration of weight training into weekly physical activity regimens was linked to a decreased risk of all-cause mortality among people with and without 

, according to an analysis of data from male health professionals in the US.

An analysis of data from the Health Professional Follow-up Study, results of the study, which included more than 30,000 men and 26 years of follow-up data, indicate integration of long-term weight training was associated with a reduction in all-cause mortality among participants without type 2 diabetes, even with adjustment for aerobic activity, while the benefits of weight training on all-cause mortality in those with type 2 diabetes appeared to be more complicated.

“Our study supports the current physical activity guidelines and provides additional evidence for the optimal amount of long-term weight training independently and jointly with aerobic activity to maximize longevity benefits in adults with and without type 2 diabetes," wrote investigators.

As the knowledge base surrounding the impact of different forms of aerobic and anaerobic activities, debate has emerged regarding the ideal amount of each form of activity as part of a person’s lifestyle routine. Without a dedicated randomized controlled trial, clinicians and researchers have turned to observational data and retrospective analyses to better understand what constitutes optimal levels of each form of physical activity in different patient groups.

To develop a greater understanding of the associations of long-term weight training and mortality in men, investigators designed the current study as an analysis of data recorded within the Health Professional Follow-up Study. Launched in 1986, the study enrolled 51,529 male health professionals aged 40-75 years. As part of the follow-up protocol, the study assessed patient information via a biennial questionnaire, which began assessments of weight training as part of their evaluations of physical activity in 1990.

Limiting their analyses to those with at least one 1 measure of weight training at baseline, investigators identified 31,140 men without type 2 diabetes and 2,588 men with type 2 diabetes for inclusion in the current study. The aforementioned questionnaires asked participants to report average weekly time spent weightlifting or using a nautilus or weight machine, with the options including 0 minutes, 1-4 min, 5-19 min, 20-59 min, 1 hour, 1-1.5 hours, 2-3 hours, 4-6 hours, 7-10 hours, or 11 or more hours. Investigators noted up to 13 repeated measures of weight training information were collected during the follow-up period, with a median of 11 measures occurring per participant.

For the purpose of analysis, Cox regression was used to estimate hazard ratios (HRs) for all-cause mortality. These models were adjusted for age, height, race, smoking status, family history of myocardial infarction, family history of cancer, baseline hypertension, alcohol consumption, AHEI score 2010, total calorie intake, time spent sitting to watch television, BMI, and aerobic activity level.

Among the 33,728 individuals included in the study, 12,607 deaths were documented, with 988 deaths occurring among men with type 2 diabetes. Upon analysis, results suggested 1-59 and 60-149 minutes per week of long-term weight training were associated with 14% (HR, 0.86 [95% CI, 0.82-0.89]) and 8% (HR, 0.92 [95% CI, 0.85-0.99]) lower mortality versus no weight training, respectively, among those without type 2 diabetes after adjustment for aerobic activity. Further analysis among men without type 2 diabetes indicated long-term weight training 150 minutes or more per week was not significantly associated with mortality (HR, 1.05 [95% CI, 0.91-1.20]; overall 

Among men with type 2 diabetes, results of the investigators’ analysis indicated those with 1-59 and 60-149 minutes per week of prediagnosis weight training had 32% (HR, 0.68 [95% CI, 0.48-0.96]) and 27% (HR, 0.73 [95% CI, 0.54-0.99]) lower risks of all-cause mortality, respectively. No decreased risk of mortality was observed for those with 150 minutes or more of per week weight training prediagnosis (HR, 1.11 [95% CI, 0.80-1.55]). Further analysis of this cohort suggested a weak inverse association between moderate levels of postdiagnosis weight training with all-cause mortality, but the association became nonsignificant after additional adjustment for postdiagnosis aerobic activity.

“Engaging in 30-60 minutes per week of long-term weight training was associated with lower risks of all-cause and cause-specific mortality, independently of aerobic activities. Moreover, the optimal benefit of mortality risk reduction was found in individuals performing above the recommended aerobic activity and any weight training,” investigators concluded. “Similar findings were observed in adults with type 2 diabetes, suggesting the benefit of engaging in moderate levels of pre- and postdiagnosis weight training, with aerobic activity, to reduce mortality.”

Long-term Weight Training and Mortality in U.S. Male Health Professionals With and Without Type 2 Diabetes

An analysis of data from the Health Professionals Follow-Up Study suggests incorporating weight training into physical activity regimens was associated with reduced mortality in patients with or without type 2 diabetes, with the association in those without diabetes present even after adjustment for aerobic activity levels. 

Incorporating Weight Training Into Physical Activity Regimen Linked to Reduced Mortality in Type 2 Diabetes

New data suggests empagliflozin (Jardiance) use was associated with significant improvements in glycemic control among pediatric patients with 

December 7 statement from Eli Lilly and Company

, results of the phase 3 DINAMO trial indicate use of empagliflozin was associated with a statistically significant reduction in HbA1c and also with a clinically meaningful reduction in fasting plasma glucose among a population of patients aged 10-17 years of age living with type 2 diabetes.

"Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it's important to recognize and treat diabetes early in its course," said Lori Laffel, MD, principal investigator of the DINAMO study and chief of the Pediatric, Adolescent, and Young Adult Section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, in Eli Lilly and Company’s statement. "Today's results from the DINAMO global clinical trial demonstrated that the SGLT2 inhibitor Jardiance compared with placebo significantly improved overall blood sugar control in children and adolescents with type 2 diabetes. These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin is the only globally available oral treatment for youth."

As the prevalence of type 2 diabetes continues to rise in adults and pediatric populations, the introduction of a therapy with the potential cardiorenal benefits, such as those demonstrated in EMPA-Kidney and EMPEROR-Reduced, for pediatric populations could stand to provide substantial benefit on a population level. Named the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO), the trial enrolled children and adolescents aged 10-17 years with type 2 diabetes an HbA1c equal to or greater than 6.5% and equal to or less than 10.5%. These participants underwent subsequent screening and randomized in a 1:1:1 manner to linagliptin 5 mg, placebo therapy, or empagliflozin in a 10 or 25 mg dose.

Overall, 262 participants underwent screening and 158 underwent randomization. Of these 158, 52 were randomized to Empagliflozin, 53 were randomized to linagliptin, and 53 were randomized to placebo therapy. Of note, all patients in the trial were treated with diet and exercise plus metformin and/or insulin or no background if considered to be metformin intolerant. The primary endpoint of interest in the trial was change in HbA1c at 26 weeks. The trial also included multiple secondary endpoints examining efficacy and safety.

Upon analysis, results of the trial demonstrated use of empagliflozin was associated with a 0.84% reduction in HbA1c relative to placebo therapy at week 26 (95% CI –1.50 to –0.19; 

=.012). The release form Eli Lilly and Company noted use of linagliptin was not associated with a statistically significant reduction in HbA1c compared with placebo therapy, with a numerical reduction of 0.34% (

In an analysis of secondary endpoints, results indicated use of empagliflozin was associated with a 35.2 mg/dL reduction in fasting plasma glucose (

=.0035). In their release, Eli Lilly and Company pointed out the overall safety data from DINAMO was generally consistent with findings in adults with type 2 diabetes.

“The rise in the prevalence of type 2 diabetes in the pediatric population highlights a clear unmet need,” said Jeff Emmick, MD, PhD, vice president, Product Development, Eli Lilly & Company, in the aforementioned release. “Having overcome the challenges in recruitment and design that pediatric trials tend to face, the outcomes of DINAMO represent another positive step forward in Boehringer Ingelheim and Lilly’s commitment to improve the lives of people living with cardio-renal and metabolic conditions such as type 2 diabetes.”

This study, “Diabetes study of Linagliptin and Empagliflozin in Children and Adolescents,” was presented at the International Diabetes Federation World Diabetes Congress 2022.

Eli Lilly and Company and Boehringer Ingelheim announced their SGLT2 inhibitor, empagliflozin, was associated with statistically significant reductions in HbA1c relative to placebo therapy among a population of pediatric patients with type 2 diabetes in the DINAMO trial.

Empagliflozin Proves Benefit in Pediatric Type 2 Diabetes in Phase 3 DINAMO Trial

Data from a randomized trial examining oral butyrate supplementation in pediatric populations suggests use of the gut microbiome-derived metabolite could be an effective strategy for treating 

Named the Butyrate Against Pediatric Obesity (BAPO) trial, results of the study, which used a decrease of at least 0.25 BMI SD scores at 6 months as the primary outcome, demonstrate use of oral butyrate 20 mg/kg body weight per day was associated with a 40% absolute increase in the rate of the primary outcome compared to placebo, with results also suggesting use was associated with superior reductions in weight circumference, HOMA-IR, and IL-6 levels.

“The findings of this study suggest that in children with obesity, oral butyrate supplementation may produce a reduction of BMI and exerts beneficial effects on glucose metabolism and inflammation,” wrote investigators. “These data support the importance of the [gut microbiome]-derived metabolite butyrate as a protective factor against obesity, highlighting the central role of a healthy diet and GM function to achieve an optimal endogenous production of butyrate.”

In recent years, both weight management and the role of gut microbiome in overall health have undergone complete revolutions. As the fields have progressed, research into the impact of gut microbiome on metabolic health, including promotion of obesity has become a focal point of many research endeavors. Citing a 2020 literature review outlining the effects of butyrate production on incidence of obesity, the BAPO trial was designed to examine whether butyrate supplementation could be an effective treatment for obesity in pediatric populations.

A randomized, quadruple-blind, parallel-group, placebo-controlled trial, BAPO randomized patients aged 5-17 years with a BMI greater than the 95th percentile to oral butyrate supplementation at 20 mg/kg body weight per day or placebo therapy for 6 months, with a decrease of at least 0.25 BMI SD scores at 6 months as the primary outcome of interest. The trial randomized 54 children with obesity to the butyrate and placebo therapy groups, with 6 patients being lost to follow-up prior to completion of the trial. The overall study population had mean age of 11 (SD, 2.91) years and 57% were female.

Investigators pointed out the trial’s intention-to-treat analysis also included multiple secondary outcomes of interest, such as changes in waist circumference, fasting glucose, insulin, total cholesterol, LDL-C, HDL-C, triglyceride, ghrelin, microRNA-221, IL-6 levels, HOMA-IR, dietary and lifestyle habits, and gut microbiome structure.

Upon analysis, results suggest those randomized to treatment with butyrate had a greater rate of BMI decrease greater than or equal to 0.25 SD at 6 months, with such a decline occurring among 96% of those receiving butyrate compared to 56% among the placebo arm (absolute benefit increase, 40% [95% CI, 21 to 61%]; 

 <.01). In the per-protocol analysis, which included the 48 not lost to follow-up, results indicated those in the butyrate arm experienced greater changes in waist circumference (−5.07 cm [95% CI −7.68 to −2.46 cm]; 

<.001), insulin level (−5.41 μU/mL [95% CI, −10.49 to −0.34 μU/mL]; 

=.03), HOMA-IR (−1.14 [95%CI, −2.13 to −0.15]; 

=.02), ghrelin level (−47.89 μg/mL [95% CI, −91.80 to −3.98 μg/mL]; 

<.001), microRNA221 relative expression (−2.17 [95% CI,−3.35 to −0.99]; 

<.001), and IL-6 level (−4.81pg/mL [95% CI, −7.74 to −1.88 pg/mL]; 

<.001) compared to their counterparts receiving placebo therapy.

Further analysis demonstrated similar patterns of adherence to standard care was observed across both study arms and baseline gut microbiome signature predictable of therapeutic response were identified as part of the analyses. Investigators pointed out mild nausea and headache were reported by 2 patients during the first month of the butyrate intervention.

“The lower adherence rate and higher frequency of mild adverse effects observed in patients treated with butyrate suggest that the unpleasant organoleptic features of this compound may limit its clinical application,” investigators concluded. “Hence, development of new butyrate-based compounds free of these unpleasant features is advocated for a more effective therapeutic action of butyrate against pediatric obesity.”

Therapeutic Effects of Butyrate on Pediatric Obesity,

Data from the BAPO trial suggests use of oral butyrate supplementation was associated with a 40% absolute increase in rate of the trial's BMI-based primary outcome at 6 months relative to placebo therapy in a population of pediatric patients with obesity. 

Oral Butyrate Supplementation Could Be Effective in Treating Pediatric Obesity

A woman in her early 40s with a history of diabetes mellitus presents to the emergency department for a flu-like illness with multiple symptoms. This morning she woke with chills, subjective fever, cough, and headache, and vomited once. She is also feeling weak all over and has dyspnea, pleuritic chest pain, and epigastric pain. She denies diarrhea, dysuria, or other symptoms.

 Temperature 102.3, Pulse 126, BP 105/45, Pulse-ox 98%. 

 is notable for a positive jolt sign but no photophobia or neck stiffness, clear lungs, epigastric tenderness and tachycardia.

Chem 7: normal except for glucose 203 and bicarb of 21

Other: UA normal. LP to rule out meningitis normal.

Re-eval: Feels a little better. Repeat vitals: Temp 100.1, HR 97, BP 96/55

Diagnose a viral syndrome and discharge home

Our latest endocrine case report features a woman in her 40s with a history of diabetes mellitus presenting with flu-like illness with multiple symptoms. Can you determine the correct diagnosis?

Endocrine Case Report: What's the Dif?

It has been nearly 30 years since the last consensus guidelines were published by the bariatric or weight loss surgery community back in 1991. While the original guidelines were heralded as a breakthrough in weight reduction therapy, Teresa LaMasters, MD, president of the American Society for Metabolic and Bariatric Surgery states,

It’s time for a change in thinking and in practice for the sake of patients. It is long overdue.

There are some important differences from 1991 to now among them a more inclusive selection criterion. But before we visit the new guidelines let’s go back to 1991 see what brought us here today. While the origins of weight loss surgery can be traced back to the 1950s when the first intestinal bypasses were performed widespread use of the modern iteration of that procedure didn’t see broad acceptance and use until the late 80s and early 1990s. With an emphasis on comorbidities such as diabetes and cardiovascular disease, weight loss surgery came into its own. Initial outcomes showed promise while complications still hindered efforts to reach a larger population of obese patients.

As with most new procedures, bariatric surgery in the early years was reserved for the most extreme cases of obesity and only included patients with body mass indices (BMI) of greater than 40 or greater than 35 if they also had several comorbid obesity-related conditions. The new guidelines suggest including patients with BMI >35 and as low as 30 when metabolic diseases are present.

Another key point in the 2022 update to bariatric guidelines is a long overdue validation of the safety and effectiveness of the collection of procedures. Central to the coming-of-age story here is the collective sentiments that:

“Metabolic and bariatric surgery is currently the most effective evidence-based treatment for obesity across all BMI classes”

“Studies with long-term follow up, published in the decades following the 1991 NIH Consensus Statement, have consistently demonstrated that metabolic and bariatric surgery produces superior weight loss outcomes compared with non-operative treatments.”

With greater than 90% of current weight loss procedures consisting of the modern Roux-en-Y Gastric Bypass and the sleeve gastrectomy, older operations have effectively been replaced with safer and more effective ones.1 While combating obesity itself is a worthwhile endeavor we are learning that weight reduction surgery dramatically changes outcomes related to metabolic diseases including diabetes and cardiovascular disease.

A recent study by scientists at Rutgers looked at cardiovascular outcomes after bariatric surgery in obese patients with nonalcoholic fatty liver diseases (NAFLD).

 They found a striking 50% reduction in cardiovascular events such as heart attacks, chest pain, and stroke after bariatric surgery.

The high prevalence of obesity in the United States coupled with cardiovascular disease remaining the leading cause of death for men and women in this country highlights the importance of this update and what it means for obese patients at risk.

Unfortunately, we are reaching far too few patients with obesity. Even before the inclusion criteria for bariatric surgery was broadened only 1 to 2% of the worlds eligible patient population end up getting weight reduction surgery each year.

 This statistic should give us all pause. That means that the vast majority of patients who may realize significant weight loss and freedom from life-threatening comorbidities are not being reached. The impact of doubling and then tripling the number of qualifying patients who receive weight loss surgery could have a staggering impact on so many diseases as well as real reductions in morbidity and mortality related to obesity.

The ASMBS guidelines serve as a wakeup call to all clinicians from the general practitioner to the general surgeon. We must share the benefits of weight reduction surgery with all our obese patients and have a frank discussion with them about the benefits versus the small risks of proceeding with surgery. While a concerted campaign to identify suitable patients is in order, we must be cautious not to ignore the guidelines. While bariatric surgery is by far the most effective and long-lasting weight reduction method for many, regular encouragement and lifestyle modification must still be the foundation on which we build better outcomes for our obese patient population.

https://asmbs.org/articles/after-30-years-new-guidelines-for-weight-loss-surgery

Elsaid MI, Li Y, Bridges JFP, Brock G, Minacapelli CD, Rustgi VK. Association of Bariatric Surgery With Cardiovascular Outcomes in Adults With Severe Obesity and Nonalcoholic Fatty Liver Disease. 

 2022;5(10):e2235003. doi:10.1001/jamanetworkopen.2022.35003

Gregory Weiss, MD, provides perspective on how improved safety of these procedures has revolutionized the way clinicians view use of bariatric and metabolic surgeries as a method for inducing weight loss in people with overweight and obesity. 

How Evolving Safety Has Changed the Outlook on Bariatric, Metabolic Surgery, with Gregory Weiss, MD

In one of the largest studies on long COVID from the United Kingdom since the pandemic began, a new analysis suggests those with an 

 and women were more likely to experience long COVID.

A community-based, web-survey study conducted in Norfolk, East England, results of the 1487-patient study demonstrate men had a 25% lower risk of post-COVID symptoms compared to women and each 1 kg/m

 increase in BMI was associated with a 3% increase in risk.

“We show that more than a half of the survey respondents who tested positive for Covid in the East of England during the first year of the pandemic went on to report long Covid symptoms,” said Vassilios Vassiliou, MD, PhD, a clinical professor of cardiac medicine atthe University of East Anglia’s Norwich Medical School, 

 “All of these people were infected in the months before the Covid vaccination programme was rolled out and they suffered from numerous new symptoms that were not present before their Covid infection.

As wave after wave of the pandemic came and went, the prominent focus among researchers and clinicians has changed as well. From use of masks to prevent spread, to the risk of thrombosis with vaccines or infection, and more, the focus for many has, now, shifted to the effects of long COVID and potential risk factors for predicting those with increased susceptibility to long COVID symptoms following infection.

Vassiliou and a team of colleagues designed the current study with the intent of developing a more comprehensive understanding of long COVID in the area surrounding University of East Anglia. With this in mind, investigators created a web-based survey that was sent to patients in Protect Norfolk and Waveney post-COVID-19 syndrome Project, which included adults with a confirmed COVID-19 infection via RT-PCR prior to December 6, 2020. This survey contains questions related to both pre-COVID health and post-COVID symptoms as well as questions pertaining to healthcare use.

The survey was sent to 6318 patients and responses were obtained from 23.5% (n=1487) of this cohort. At the time of the survey, 11 respondents had received their first dose of the COVID mRNA BNT162b2 vaccine. The cohort of respondents had a mean age of 50 (SD, 18.1), 61% were female, and, among the 879 with BMI measurements available, the mean BMI was 28.4 (SD, 6.9) kg/m

. Of the 1487 respondents, 774 experienced post-COVID-19 syndrome symptoms.

For the purpose of analysis, investigators used logistic regression analysis to estimate associations between potential predictors for long COVID symptoms and future healthcare utilization. Investigators pointed out baseline characteristics of the study cohort were obtained from National Health Service digital databases.

Upon analysis, results indicated male sex compared to female sex was considered a protective factor against post-COVID symptoms (RR, 0.748 [95% CI, 0.605-0.924]) while BMI was associated with an increased risk of developing symptoms (Per 1 kg/m

: RR, 1.031 [95% CI, 1.016-1.047]). Of the 1487 respondents, 25.4% reported use of health care services following their index COVID-19 infection, with 73.2% of these patients reporting post-COVID symptoms.

When assessing factors associated with further health care service use, results suggested male sex (RR, 0.618 [95% CI, 0.464-0.818]) was associated with a reduction in risk while BMI (RR, 1.027 [95% CI, 1.009-1.046]) was associated with an increased likelihood of using further health care services. Investigators highlighted experiencing post-COVID-19 symptoms was associated with a more than 3-fold increase in likelihood of using health care services (RR, 3.280 [95% CI, 2.540-4.262]).

“We hope that our work will help policymakers plan local services and also inform the wider public of the scale of the long COVID pandemic,” Vassiliou added in the aforementioned statement.

Post-COVID-19 syndrome risk factors and further use of health services in East England