Obesity in Type 1 Diabetes: A Two-Way Road Filled With Potholes

Miriam E. Tucker

October 05, 2021

Obesity in people with type 1 diabetes hasn't been a focus of research or clinical management in the past, but experts in the United States and Europe now recognize it as a unique problem and are beginning to take a closer look at options for prevention and management.

Bart Van der Schueren, MD, PhD, of the department of endocrinology at University Hospitals Leuven, Belgium, gave a talk entitled, "Type 1 diabetes and obesity: A two-way road filled with potholes," on October 1 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

"I think it's definitely underexposed and that's why we wanted to bring it to the table. We always talk about weight and weight management in the type 2 diabetes setting, but actually in type 1 diabetes, obesity is becoming more and more prevalent," he told Medscape Medical News.

In fact, in some countries the prevalence of overweight and obesity among people with type 1 diabetes exceeds that of the general population, such as for overweight (body mass index [BMI] 25-29.9 kg/m2) in Austria (39.8% vs 33.1%). In other places the prevalence is roughly the same, such as for obesity (≥ 30 kg/m2) in Belgium (17.1% vs 21.2%) and overweight in the United States (29.7% vs 31.1%), compared with the general population.

Regardless, rates appear to be rising, especially among children and adolescents with type 1 diabetes. Overweight or obesity is often present at the time of diagnosis, and rapid increases in weight are common after initiation of intensive insulin therapy, Van der Schueren noted.   

"In all the trials, you see when you intensify insulin treatment to get better glycemic control it comes at the cost of weight gain. It's not talked about often enough by clinicians and endocrinologists because the main focus is on glycemia, but this should be something we take into account when we treat patients," he said.

Van der Schueren has also coauthored a review paper, entitled, "Obesity in people living with type 1 diabetes," which was simultaneously published in The Lancet Diabetes & Endocrinology to coincide with his EASD presentation.

Could Obesity Accelerate Destruction of Beta Cells?

The relationship between type 1 diabetes and obesity may be bidirectional, said Van der Schueren.

The "two-way road" part of the title of his talk refers to the "accelerator hypothesis," which suggests that obesity itself could accelerate beta-cell destruction, which is supported by studies showing earlier onset of type 1 diabetes in people with obesity.

These factors cause a "vicious cycle" of insulin-associated weight gain leading to insulin resistance, necessitating higher doses of insulin.

"It's a bigger circle that needs to be broken," he said.

Asked to comment, M. Sue Kirkman, MD, emerita professor of medicine at the University of North Carolina, Chapel Hill, told Medscape Medical News: "I think it's a very important area...We think of type 1 diabetes in kids...but people are living a long time with it."

"We have to get out of the mindset that we can prevent all these [microvascular] complications and people do just fine. Actually, there's also cardiovascular disease and other things," she added.

Having Type 1 Diabetes Complicates Weight Loss

Compounding the problem, said Van der Schueren, is that weight loss is more challenging for people with type 1 diabetes, in part, because of the risk for hypoglycemia with diet and exercise, necessitating corrective eating to correct and sometimes involving "defensive snacking" to prevent, as well as avoidance of exercise.   

Kirkman noted, "There's no simple solution to obesity, but I think [it's] particularly [difficult] when you have people who have to take insulin and have to treat hypoglycemia and can't just go on a completely restrictive diet without thinking too much about it."

The two newer type 2 diabetes drug classes that have shown weight loss benefits, the glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, are not approved for type 1 diabetes in the United States.

In Europe, the SGLT2 inhibitors sotagliflozin and dapagliflozin are approved as adjuncts to insulin therapy in certain patients with type 1 diabetes.

Overall, Van der Schueren said these drugs are "underused" in people with type 1 diabetes and overweight/obesity because "they have restrictive marketing authorizations across the world, and this is because regulators are still very glucose-centric in their approach. Also, the drugs come at a high cost and often are not reimbursed. And, of course, the type 1 diabetes market is relatively small, so it's less interesting for companies to invest in."

Studies of liraglutide in type 1 diabetes have shown significant weight loss (up to 5 kg) but only modest reductions in A1c (0.2%), "and this is not usually enough to convince regulators of the value of those drugs...I think we should move beyond A1c as the sole measure of effectiveness of these drugs," Van der Schueren said.

The SGLT2 inhibitors are typically less effective at reducing weight compared with GLP-1 receptor agonists and can be problematic in type 1 diabetes due to the increased risk for diabetic ketoacidosis. Patients need to be educated on how to monitor ketones and treat if necessary, he pointed out.

Bariatric surgery has shown some benefit in people with type 1 diabetes, but further investigation is needed, he observed.  

Initiatives Aim to Gather Data, Inform Future Guidelines

Van der Schueren and his coauthors of the review are involved in an initiative called SOPHIA (Stratification of Obese Phenotypes to Optimize Future Obesity Therapy) to study the relationship between type 1 diabetes and weight. SOPHIA is part of the Innovative Medicines Initiative, which is jointly funded by the European Union and European pharmaceutical industry.

In the United States, a consortium called ACT1ON (Advancing Care for Type 1 Diabetes and Obesity Network) began a pilot study in 2016 funded by the National Institutes of Health designed "to identify acceptable and effective dietary strategies to optimize both glycemic control and weight management in young adults with type 1 diabetes."

The COVID-19 pandemic disrupted that trial, but preliminary results will be presented at the upcoming meeting of the International Society for Pediatric and Adolescent Diabetes (ISPAD), lead investigator Elizabeth Mayer-Davis, PhD, director of the Nutrition Obesity Research Center at the University of North Carolina, Chapel Hill, told Medscape Medical News.

The aim of ACT1ON is to produce clinical guidelines for prevention and management of obesity as part of routine type 1 diabetes management, but data will be needed first, Mayer-Davis said.

"The key is evidence base. There are very, very few studies that focus on approaches to weight management in type 1 diabetes, and very few on energy regulation...Any clinical practice guidelines need to be well-founded in rigorous studies to provide a solid evidence base. Our goal is to contribute to that evidence base. This is a long-term effort. More studies will certainly be needed beyond our pilot...done by our group and by others in the field," Mayer-Davis said.

Weight Management: A Brief Mention in New Type 1 Diabetes Guidance

Weight management is mentioned only briefly in the new American Diabetes Association/EASD consensus statement on type 1 diabetes management, also published during the EASD meeting.

In the insulin treatment section, clinicians are advised to review concerns about weight gain with insulin treatment "and discuss strategies to avoid undesirable weight gain."

The nutrition therapy section notes that BMI in individuals with type 1 diabetes is rising faster than the general population and advises that "weight loss and maintenance interventions involving nutritional advice and physical activity should be offered to individuals with type 1 diabetes who have overweight or obesity."

Van der Schueren believes it should have gone farther. "It puts all the responsibility with the patient. 'If you educate the patient, they won't gain weight' — it's not that simple."

Kirkman, a coauthor of the consensus statement, acknowledged: "There was so much to cover, and we didn't want to write a textbook. We made a decision not to cover complications in general and we included cardiovascular disease in that. But I do think it would be good to focus more on it next time."

Van der Schueren said: "I think the main thing is we need more research. We should really see how we can help people with type 1 diabetes control their weight. I think now we leave them a bit too much alone in this."

The review by Van der Schueren and colleagues was supported by SOPHIA. Van der Schueren also received a senior clinical research fellowship from the Flemish Research Council. Mayer-Davis has received research funding from the National Institute of Diabetes and Digestive and Kidney Diseases. Kirkman has reported no relevant financial relationships.

EASD 2021. Presented October 1, 2021.

Lancet Diabetes Endocrinol. Published online September 30, 2021. Abstract

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.

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