Obesity

Posted on Diabetes, Obesity, Weight Loss

The potential to enhance the effectiveness of commonly used weight-loss medications.

Weight loss
Weight loss

According to new research from the University of Michigan, a network of proteins found in the central nervous system could be harnessed to increase the effectiveness and reduce the side effects of popular diabetes and weight-loss drugs. 

The study, appearing today in the Journal of Clinical Investigation, focused on two proteins called melanocortin three and melanocortin 4, found primarily on the surface of neurons in the brain. These proteins play a central role in regulating feeding behaviour and maintaining the body’s energy balance.

Melanocortin 3 and melanocortin 4 impact everything from sensing long-term energy stores to processing signals from the gut regarding short-term fullness or satiety, said U-M physiologist Roger Cone, who led the study.

The class of drugs known as GLP-1 agonists, which includes semaglutides (e.g., Ozempic) and tripeptides (e.g., Mounjaro), has received substantial attention recently for their effectiveness in treating not only type 2 diabetes but also obesity, heart disease, and potentially addiction. They work by mimicking a natural hormone that the gut produces when it is full, triggering the brain to reduce feeding behavior.

“So the obvious question for us was: How do these GLP-1 drugs, which work by manipulating satiety signals, function when we prime the melanocortin system?” said Cone, professor of molecular and integrative physiology at the U-M Medical School and director of the U-M Life Sciences Institute where his lab is located.

Working in mouse models, Cone and his colleagues tested the effects of several hormones that reduce food intake. They compared the results in normal mice with mice that genetically lacked the MC3R protein, in mice that were given chemicals to block the activity of MC3R, and in mice that were given a drug to increase the activity of MC4R. (Because MC3R is a natural negative regulator of MC4R, meaning it decreases the activity of MC4R, blocking MC3R and increasing MC4R activity has similar effects.)

In all cases, Naima Dahir, the study’s first author and a postdoctoral research fellow in Cone’s lab, and colleagues found that adjusting the melanocortin system—either by inhibiting MC3R or increasing MC4R activity—made the mice more sensitive to GLP-1 drugs and other hormones that affect feeding behavior. The mice that were given a GLP-1 drug in combination with an MC4R agonist or MC3R antagonist showed up to five times more weight loss and reduced feeding than mice receiving only the GLP-1 drugs.

“We found that activating the central melanocortin system hypersensitizes animals to the effects of not just GLP-1s, but to every anti-feeding hormone we tested,” Cone said.

The researchers also measured activity in parts of the brain thought to trigger nausea in response to GLP-1 drugs and observed no increased activation when GLP-1 drugs were combined with alterations to the melanocortin system. In contrast, priming of the melanocortin neurons significantly increased GLP-1 drug activation of neurons in hypothalamic feeding centers in the brain.

The findings indicate that pairing the existing GLP-1 drugs with an MC4R agonist could increase sensitivity to the desired effects of the drugs by up to fivefold, without increasing unwanted side effects. Ultimately, this approach could enable patients who are sensitive to the side effects to take a lower dose, or could improve the results in patients who have not responded to the existing drug dosages. Further drug development and clinical testing are needed before this can occur.

While this research has been conducted only in mouse models, Cone is optimistic that the results will translate well to humans.

“The melanocortin system is highly conserved in humans,” he said. “Everything we’ve observed in the mouse over the past decades studying these proteins has also been found in humans, so I suspect that these results would also be translatable to patients.”

Posted on Diabetes, Exercise, Obesity

In the evening, physical activity improves glucose regulation in overweight and obese adults.

adult with obesity practicing running

Adults with obesity practising running CREDIT University Of Granada

The results, obtained by a team of scientists from the University of Granada (UGR), could have multiple practical implications, especially for people at risk of developing insulin resistance or type 2 diabetes.

The UGR’s PROFITH CTS-977 Research Group, in collaboration with the “San Cecilio” and “Virgen de las Nieves” University Hospitals in Granada; the Public University of Navarre; the Centre for Networked Biomedical Research on Physiopathology of Obesity and Nutrition (CIBEROBN); and the Centre for Networked Biomedical Research on Frailty and Healthy Ageing (CIBERFES), has studied the effect of accumulating moderate-to-vigorous physical activity on glucose levels in overweight and obese adults.

Physical activity is known to positively affect glucose regulation, but does it matter what time of day we do it? It was previously unknown whether being more active at a particular time of day (morning, afternoon or evening) could maximise the cardiometabolic benefits of physical activity. “Choosing the ideal time of day seems to be an emerging strategy to enhance the benefits of physical activity on glucose metabolism, especially for those with insulin resistance or at risk of developing type 2 diabetes,” the researchers note.

The study results show that accumulating more moderate-to-vigorous physical activity in the evening, i.e. between 18:00 and 00:00, appears to have a positive effect on glucose regulation in men and women who are overweight or obese. In addition, the benefits of physical activity are greater in people with some form of impaired glucose metabolism, such as elevated glucose levels, glycated haemoglobin and/or fasting insulin resistance index. The results were similar for both men and women.

A total of 186 overweight or obese adults (50% of whom were women) with an average age of 47 years took part in the study. These participants wore an accelerometer and a continuous glucose monitor for 14 days to measure their physical activity and glucose levels 24 hours a day. Days were classified as “inactive” if no physical activity was recorded; as “morning”, “afternoon”, or “evening” if more than 50% of the recorded minutes of physical activity for that day were registered between 6:00-12:00, 12:00-18:00 or 18:00-00:00, respectively; or as “mixed” if none of these defined time periods accounted for more than 50% of the physical activity for that day.

The results could have several practical implications, especially for those at risk of developing insulin resistance or type 2 diabetes, and highlight the importance of considering the time of day when prescribing physical activity. This information may be crucial in improving the effectiveness of exercise interventions in these groups.

Posted on Diabetes, Obesity

A new study shows the long-term effectiveness of gastric bypass in treating type 2 diabetes and obesity.

Diabetes in remission for 15 years, weight loss maintained for 20 years in large study
In a large study, diabetes was in remission for 15 years, and weight loss was maintained for 20 years.
Roux-en-Y gastric bypass, a type of weight-loss surgery, kept type 2 diabetes in remission for up to 15 years and most of the weight off for up to 20 years in one of the largest long-term studies of patients undergoing the procedure. The study* was presented today at the American Society for Metabolic and Bariatric Surgery (ASMBS) 2024 Annual Scientific Meeting.

Researchers from Geisinger Medical Center in Danville, PA, analyzed diabetes remission rates and weight-loss outcomes of 2,045 patients who had a gastric bypass at their centre between 2001 and 2008 and followed them for up to 20 years. Before surgery, patients, on average, were 46 years old with a body mass index (BMI) of 47.9.

Of the 677 patients with pre-operative diabetes, remission rates were 54% at the three-year mark but dropped to 38% after 15 years. Only about 10% of patients with insulin-dependent diabetes had remission in the same timeframe, and the rate of persistent diabetes was higher in patients who had insulin-treated diabetes before surgery. 
After 18 months, peak weight loss of 31.8% was achieved, stabilizing at 23% after 10 years and up to the 20-year mark. The overall 15-year mortality rate was 13.3%, which was 37.4% among patients with diabetes and older than 60. No deaths were related to the surgical procedure itself.
“With the availability of medical and endoscopic therapies, the demonstration of the long-term effectiveness of gastric bypass that exceeds that of these alternatives is critical to providing the right intervention for the right patient at the right time,” said study author Anthony T. Petrick, MD, FACS, Director, Division of Bariatric and Foregut Surgery, Geisinger Health System.
The ASMBS reports that nearly 280,000 metabolic and bariatric procedures were performed in 2022, representing only about 1% of those who meet eligibility requirements based on BMI.
“The study is an important contribution to the current understanding of long-term outcomes of gastric bypass because of the extremely high follow-up rates,” said Marina Kurian, MD, ASMBS President, who was not involved in the study.
According to the U.S. Centers for Disease Control and Prevention (CDC), obesity affects 42.4% of Americans. Studies show the disease can weaken or impair the body’s immune system and cause chronic inflammation, and increase the risk of many other diseases and conditions including cardiovascular disease, stroke, type 2 diabetes, and certain cancers. 
About Weight-Loss Surgery
Posted on Diabetes, Obesity

A new study shows metabolic and bariatric surgery prevents pre-diabetes from developing into type 2 diabetes in most patients.

Study: 40-year follow up shows significant reduction in death rates after bariatric surgery

Patients with pre-diabetes and severe obesity who had metabolic and bariatric surgery were 20 times less likely to develop full-blown type 2 diabetes over the course of 15 years than patients with the condition who did not have surgery, according to a new study* presented today at the American Society for Metabolic and Bariatric Surgery (ASMBS) 2024 Annual Scientific Meeting.

Only 1.8% of patients progressed to a diagnosis of diabetes in five years after metabolic surgery (Roux-en-Y gastric bypass or sleeve gastrectomy), which rose to 3.3% in 10 years and 6.7% after 15 years. The protective effect against diabetes was higher among gastric bypass patients. Greater weight loss at three years was associated with a lower risk of progression to diabetes.

“This is the first study to analyze the long-term impact of metabolic and bariatric surgery on the potential progression of prediabetes, and the impact is significant and durable,” said David Parker, MD, study co-author and a bariatric surgeon at Geisinger Medical Center in Danville, PA. “It demonstrates that metabolic surgery is as much a treatment as a prevention for diabetes.”

Prediabetes is a serious condition that occurs when blood sugar levels are higher than normal but not high enough to be considered type 2 diabetes. According to the CDC, approximately 98 million Americans — more than 1 in 3 — have prediabetes and 38.4 million have diabetes.

This retrospective study included 1,326 patients who had prediabetes before undergoing either Roux-en-Y gastric bypass (n= 1,154) or sleeve gastrectomy (n= 172) between 2001 and 2022. Non-surgical controls from a primary care cohort were propensity-matched by haemoglobin A1c, age, sex, and body mass index (BMI). More than 80% of patients were female, an average of 45 with a mean BMI of 46.9 and a median follow-up of 7.2 years.

“Think of all the negative health consequences that diabetes patients may avoid through metabolic surgery,” said Marina Kurian, MD, ASMBS President, who was not involved in the study. “Prevention of diabetes is the best treatment.”

The ASMBS reports that nearly 280,000 metabolic and bariatric procedures were performed in 2022, representing only about 1% of those who meet eligibility requirements based on BMI. According to the U.S. Centers for Disease Control and Prevention (CDC), obesity affects 42.4% of Americans. Studies show the disease can weaken or impair the body’s immune system, cause chronic inflammation, and increase the risk of many other diseases and conditions, including cardiovascular disease, stroke, type 2 diabetes, and certain cancers.

Posted on Obesity, Pain Management

Body Image & Pain

Body image is a psychosocial construct often ignored in health management discussions, even though evidence suggests that it can play an important role in shaping overall well-being. During the March 2024 Pain Science Lecture Series, Dr. Yazmine Huizar outlined the interconnection between pain, obesity, and depression. She also explored how targeted body image interventions can enhance outcomes across multiple domains.