• Mihoko Yoshino, Brandon D Kayser, Jun Yoshino, Richard I Stein, Dominic Reeds, EagonJ ChristopherJCFrom the Center for Human Nutrition (M.Y., B.D.K., J.Y., R.I.S., D.R., K.S., B.W.P., S.K.) and the Department of Surgery (J.C.E., S.R.E.), Washington University School of Medicine, St. Louis; and the Departments of Medicine (J.D.W., M., Shaina R Eckhouse, Jeramie D Watrous, Mohit Jain, Rob Knight, Kenneth Schechtman, Bruce W Patterson, and Samuel Klein.
• From the Center for Human Nutrition (M.Y., B.D.K., J.Y., R.I.S., D.R., K.S., B.W.P., S.K.) and the Department of Surgery (J.C.E., S.R.E.), Washington University School of Medicine, St. Louis; and the Departments of Medicine (J.D.W., M.J.), Pharmacology (J.D.W., M.J.), Pediatrics (R.K.), and Computer Science and Engineering (R.K.), University of California San Diego, San Diego.
• N. Engl. J. Med. 2020 Aug 20; 383 (8): 721732721-732.

BackgroundSome studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.MethodsWe evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp). Secondary outcomes were changes in muscle insulin sensitivity, beta-cell function, and 24-hour plasma glucose and insulin profiles.ResultsWeight loss was associated with increases in mean suppression of glucose production from baseline, by 7.04 μmol per kilogram of fat-free mass per minute (95% confidence interval [CI], 4.74 to 9.33) in the diet group and by 7.02 μmol per kilogram of fat-free mass per minute (95% CI, 3.21 to 10.84) in the surgery group during clamp stage 1, and by 5.39 (95% CI, 2.44 to 8.34) and 5.37 (95% CI, 2.41 to 8.33) μmol per kilogram of fat-free mass per minute in the two groups, respectively, during clamp stage 2; there were no significant differences between the groups. Weight loss was associated with increased insulin-stimulated glucose disposal, from 30.5±15.9 to 61.6±13.0 μmol per kilogram of fat-free mass per minute in the diet group and from 29.4±12.6 to 54.5±10.4 μmol per kilogram of fat-free mass per minute in the surgery group; there was no significant difference between the groups. Weight loss increased beta-cell function (insulin secretion relative to insulin sensitivity) by 1.83 units (95% CI, 1.22 to 2.44) in the diet group and by 1.11 units (95% CI, 0.08 to 2.15) in the surgery group, with no significant difference between the groups, and it decreased the areas under the curve for 24-hour plasma glucose and insulin levels in both groups, with no significant difference between the groups. No major complications occurred in either group.ConclusionsIn this study involving patients with obesity and type 2 diabetes, the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, with no evident clinically important effects independent of weight loss. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02207777.).Copyright © 2020 Massachusetts Medical Society.

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