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.

Figure 1

Glucostatic and pancreatic hormone changes. Changes in glucose (A), insulin (B), C-peptide (C), and glucagon (D). E: Changes in insulin secretion relative to glucose. F: Changes in metabolic insulin clearance. G: MI at baseline. H: MI after 1 year. I: Regression analysis of MI after 1 year and percentage of weight loss. J: Regression analysis of oDI after 1 year and percentage of weight loss. LS/IMM is depicted in blue and RYGB is depicted in red. Open shapes and dashed lines denote baseline values, and closed shapes and solid lines denote values at 1 year. Hatched bars denote baseline values, and solid bars denote values at 1 year. AUC is calculated from 0 to 120 min and is expressed ×10³. M0, month 0 (baseline); M12, month 12. *P < 0.05 for within-group change. §P < 0.05 for difference in change between groups.

Figure 2

Fasting and postprandial changes in GLP-1 (A), GIP (B), and GLP-2 (C). Values are depicted in blue for LS/IMM and in red for RYGB. Open shapes and dashed lines denote baseline values, and closed shapes and solid lines reflect values at 1 year. Hatched bars denote baseline values, and solid bars denote values at 1 year. AUC is calculated from 0 to 120 min and is expressed ×10³. M0, month 0 (baseline); M12, month 12. *P < 0.05 for within-group change. §P < 0.05 for difference in change between groups.