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Symposium compares models for unlocking the mechanisms of obesity

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As researchers continue to work to identify the mechanisms of obesity, two competing models have emerged: the carbohydrate-insulin model (CIM) and the energy-balance model (EBM). As with many scientific debates and controversies these days, much of the discussion plays out through social media.

During the session Twitter Bugs—Dancing between the Carbohydrate-Insulin and Energy-Balance Models, a pair of renowned researchers who also both happen to be active users of X (the social media platform formerly known as Twitter), discussed the scientific merit of and the hypotheses driving the two models, which have significantly different implications for clinical management.

The session can be viewed on-demand by registered meeting participants at ADA2023.org. If you haven’t registered for the 83rd Scientific Sessions, register today to access the valuable meeting content through August 28.

James D. Johnson, PhD
James D. Johnson, PhD

James D. Johnson, PhD (@JimJohnsonSci), Professor of Medicine in the Department of Cellular and Physiological Sciences and Director of the Life Sciences Institute at the University of British Columbia in Vancouver, Canada, began with an overview of CIM, which suggests that obesity is driven by the consumption of rapidly digestible carbohydrates.

“When we talk about obesity, I think it’s really important to think about whether we are discussing weight gain, that is, how somebody from the time they’re born or even before they’re born develops adipocytes, or if we are talking about the maintenance of body weight or how weight loss happens,” Dr. Johnson said. “I think this is really important because sometimes we find a mechanism for weight loss and we infer that it’s the reverse of the mechanism of weight gain. But I think the mechanisms of these three things can be, in some cases, completely distinct.”

In both models of obesity, the hypotheses and the questions being studied center around understanding the primary driver, or drivers, of obesity and defining causality, he noted.

“It really comes down to a question of directionality,” Dr. Johnson said. “The key thing to remember is that what’s called the carbohydrate-insulin model is really two parts: Do the carbs affect the insulin, and then does the insulin affect the obesity? It’s really a hormone-centric, adipocyte-centric model with insulin as a somewhat tissue-specific growth factor.”

Kevin D. Hall, PhD
Kevin D. Hall, PhD

Kevin D. Hall, PhD (@KevinH_PhD), Senior Investigator at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, followed with an overview of EBM, which argues that the increased prevalence of obesity has resulted from changes in the food environment leading to increased intake.

Body weight is regulated by the brain in response to external signals from the food environment that are integrated with neuroendocrine signals to control food intake below conscious awareness, he explained.

“CIM focuses on adipose tissue, but I believe that is unlikely to explain the increasing prevalence of obesity,” Dr. Hall said. “It might very well be important for some individuals and explain why some individuals are susceptible to diets that increase insulin; although it’s probably basal insulin and not postprandial insulin.”

In contrast, he said EBM focuses on the brain and suggests that increasing obesity prevalence results from multifactorial changes in the increasingly ultra-processed food environment. He cited findings from a study that suggested that both carbohydrate and fat restriction can lead to changes in basal insulin. 

“We still have a lot to learn about how changes in the food environment are actually affecting the neuroendocrine systems regulating body weight. These internal signals that are being integrated as part of this—changes in gut hormones, changes in insulin—might be very important,” Dr. Hall said.