Effects of Gastric Bypass on Beta-cell function and Insulin sensitivity in Patients with Non-Severe Obesity (BMI<35 kg/m2) and Insulin-treated Type 2 Diabetes.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes (T2D), but the physiological mechanisms underlying sustained improvements in glycemic control remain incompletely understood. OBJECTIVE: To descriptively compare short- and long-term changes in glycemic control and insulin secretion dynamics following RYGB or best medical care (BMC) using an intravenous glucagon stimulation test (GST) in patients with non-severe obesity (BMI <35 kg/m2) and insulin-treated T2D. METHODS: Thirty-five patients with long-standing insulin-dependent T2D were enrolled from two prospective studies and received either BMC or RYGB. GST was performed at baseline and repeated after 3, 6, 12 and 24 months. Changes in glucose, insulin, and C-peptide responses were analyzed. Exploratory indices derived from the GST were used to assess longitudinal within-subject changes. RESULTS: Diabetes remission occurred in 10% of patients in the RYGB group versus 0% in the BMC group. Insulin therapy was discontinued in 73% versus 33%, while oral antidiabetic medication was discontinued in 33% vs. 0%. After 24 months HbA1c, BMI and use of antidiabetic medication were lower in the RYGB group. Insulin secretion rapidly decreased and remained lower over 24 months after RYGB, while C-peptide responses were largely stable and glycemic control improved. Exploratory GST-derived indices increased after RYGB but not after BMC. CONCLUSION: In this descriptive and exploratory analysis, RYGB was associated with changes consistent with improved metabolic efficiency, reflected by enhanced glycemic control and reduced insulin secretion requirements under intravenous stimulation testing conditions. These findings are hypothesis-generating and warrant confirmation in larger, methodologically controlled studies.