Preserved Insulin Secretory Capacity and Weight Loss Are the Predominant Predictors of Glycemic Control in Patients With Type 2 Diabetes Randomized to Roux-en-Y Gastric Bypass

Abstract

Improvement in type 2 diabetes after Roux-en-Y gastric bypass (RYGB) has been attributed partly to weight loss, but mechanisms beyond weight loss remain unclear. We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins, insulin sensitivity, and secretion 1 year after randomization to lifestyle modification and intensive medical management (LS/IMM) alone (n = 34) or in conjunction with RYGB (n = 34). The RYGB group lost more weight and had greater improvement in HbA1c. Fasting glucose was lower after RYGB than after LS/IMM, although the glucose area under the curve decreased comparably for both groups. Insulin sensitivity increased in both groups. Insulin secretion was unchanged after LS/IMM but decreased after RYGB, except for a rapid increase during the first 30 min after meal ingestion. Glucagon-like peptide 1 (GLP-1) was substantially increased after RYGB, while gastric inhibitory polypeptide and glucagon decreased. Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups. At baseline, a greater C-peptide index and 90-min postprandial C-peptide level were predictive of lower HbA1c at 1 year after RYGB. β-Cell glucose sensitivity, which improved only after RYGB, and improved disposition index were associated with lower HbA1c in both groups, independent of weight loss. Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB.

Effect of Laparoscopic Sleeve Gastrectomy on Fasting Gastrointestinal, Pancreatic, and Adipose-Derived Hormones and on Non-Esterified Fatty Acids

“…Similar findings have been reported for RYGB [35, 36]. Another study demonstrated an early attenuation of the glucagon response to a mixed meal early after both LSG and RYGB, but fasting glucagon levels were similar to preoperative values at 1 year after either operation type [13].…”

Beta‐cell sensitivity to glucose is impaired after gastric bypass surgery

“…The hyperinsulinaemia that accompanies rapid rates of prandial glucose appearance and clearance in GB patients has been taken as evidence that surgery enhances β‐cell function. In fact, previous studies implicate increased incretin stimulation, as well as greater β‐cell glucose responsiveness after eating, to explain higher rates of insulin secretion. The findings presented here support a dramatically different model of surgical effects on insulin secretion.…”

“…Indeed, GB increases the incretin effect in both diabetic and non‐diabetic individuals, and the effect of GLP‐1 to stimulate insulin release increases more than 2‐fold . Modelling of plasma C‐peptide concentrations in GB subjects after meals also suggests increased β‐cell sensitivity to glucose . However, the complexity of insulinotropic stimuli in surgical patients makes attribution of factors controlling insulin secretion difficult.…”

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations

“…However, T2D is a progressive disease associated with increased risk for CVD and microvascular complications. Furthermore, evidence shows that metabolic improvement following surgery in patients with T2D correlates with shorter diabetes duration at baseline, possibly reflecting more preserved b-cell function (19,52,96). This suggests that unnecessarily delaying access to surgery might reduce health benefits and cost-effectiveness of surgery in patients with diabetes.…”