Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

The role of the gut in diabetes remission after Roux-en-Y gastric bypass (RYGB) is incompletely understood. We assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Longitudinal, prospective measures of β-cell function were assessed after oral glucose intake and graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n = 29), 12 (n = 24), and 24 (n = 20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. The decreases in body weight, fat mass, waist circumference, and insulin resistance after surgery (all P < 0.001 at 12 and 24 months) did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose intake differed by remission status (P = 0.04): greater (6.5-fold; P < 0.01) and sustained in those in full remission, moderate and not sustained past 12 months in those with partial remission (3.3-fold; P < 0.001), and minimal in those not experiencing remission (2.7-fold; P = not significant). The improvement in β-cell function after IV glucose administration was not apparent until 12 months, significant only in those in full remission, and only ∼33% of that observed after oral glucose intake. Preintervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.