Long Term Effects on Metabolic Parameters of Significant Weight Reduction (>25%) by Very Low Calorie Diet Compared to Roux-en-Y Gastric Bypass in Diabetic Obese vs Obese Without Diabetes (Patients vs Nonhuman Primates)

Abstract

Background: Obesity has similar effects in both monkeys and humans, including the development of metabolic syndrome, which is often followed by type 2 diabetes mellitus (DM). The effects of short term and intermittent very low-calorie diets (VLCD) suggest improvement in glycemic control, however, the long term (two year or more) effects of a VLCD have not been examined in obesity with or without diabetes. Methods: The metabolic and glycemic effects of major weight reduction in nonhuman primates using VLCD was compared to major weight reduction in humans using gastric bypass at 2 years post-surgery. In 14 spontaneously obese rhesus monkeys, half with overt T2DM were compared to 18 obese humans, ten with DM and eight without (OB). All humans underwent Roux-en-Y gastric bypass surgery and were followed for two years. The metabolic indices of the NHP and humans were obtained at the beginning and end of the two-year period. Results: All four groups experienced significant weight loss ranging from 22% to 37% reduction. Fasting glucose decreased significantly in both DM groups but were unchanged in both obese groups. In both humans and monkeys, fasting glucose of the DM and OB groups initially differed significantly from each other, but after surgery and after VLCD, did not differ. ß cell function, assessed by the acute insulin response to IV glucose, decreased in both OB groups and increased in both DM groups. In both species, after weight loss, the OB groups retained a higher acute insulin response compared to the DM groups, however, the differences between the OB and DM groups were significant (p-value of 0.032 for monkeys and 0.03 in humans). Insulin sensitivity in humans increased in both DM and OB groups (p <0.001 and 0.003, respectively). However, there was a larger change in the OB group. Conclusion: These results demonstrate a significant improvement in glycemic control (temporarily) from both long-term very low-calorie diets and gastric bypass. Pancreatic ß-cell function, however, cannot be restored to normal, even after significant weight loss (and sustained weight loss maintenance) in the diabetic groups. These results strongly support much earlier intervention to reduce obesity long before T2DM develops, as the reversibility of ß-cell defects disappears with overt T2DM, despite some limited improvement in glycemia. NIH grants NO1AG3 1012, NIA, and NIDDK This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.