Beneficial Effects of RYGB on ß-Cell Function and Hepatic and Peripheral Insulin Sensitivity Are Maintained Seven Years after Surgery in Both Diabetic and Nondiabetic Subjects

Gastric bypass surgery (RYGB) leads to improvement or remission of type 2 diabetes (T2D). Long-term studies indicate that the remission rate is higher 2 than 10 years post-surgery; whether the positive effects of surgery on ß-cell function (ß-GS) and glucose metabolism are maintained long term after surgery has not been determined. We studied 21 patients (12 T2D and 9 nondiabetic (ND)) before (B), 1 (1y) and 7 years (7ys) after RYGB with the use of a mixed meal test (MTT) in combination with glucose tracers to measure postmeal glucose fluxes and a euglycemic insulin clamp for insulin sensitivity (M). ß-GS (insulin secretion and dose response curve) was assessed by mathematical modelling. Weight loss 1y after RYGB was 30% and 35% of initial weight for ND and T2D respectively, and 24% and 30% at 7ys. T2D was resolved 1y post surgery in T2D and this outcome was maintained at 7ys (HbA1c 58±4 vs. 35±1 vs. 41±2 mmol/mol; B, 1y and 7ys). M value improved at 1y in proportion to the weight lost (5.0±0.8 to 7.2±0.7 in ND, and 4.3±0.8 to 7.5±0.7 mg. kgffm-1. min-1 in T2D, p<0.01 for both), and was maintained at 7ys (7.0±0.8 in ND and 6.9±0.9 mg.kgffm-1. min-1 in T2D, p=ns vs. 1y). Plasma glucose profiles were similar in ND and T2D at 1y and 7ys. After RYGB, most of the oral glucose appeared in the circulation in the first 90 min after meal ingestion in both groups and the dynamic of the oral glucose Ra was unchanged at 7ys. Suppression of endogenous glucose production (EGP) was improved in both groups during the first 90 min at 7ys compared to 1y; in T2D, mean EGP was significantly decreased. In T2D, the improvement in ß-GS seen at 1y (34±6 to 67±11 pmol.min-1.m-2.mM-1, p=0.001) was maintained at 7ys (80±21) at a similar level as in ND (138±18 vs. 87± 9 vs. 82±11, B, 1- and 7ys). Conclusion: In both ND and T2D, RYGB induces marked improvements in glucose tolerance, insulin sensitivity (both muscle and hepatic) and ß-cell function that are maintained 7 years after surgery. Disclosure S. Camastra: None. B.D. Astiarraga: None. C. Barbieri: None. M. Gaggini: None. M. Palumbo: None. R. Berta: None. D. Ciociaro: None. M. Anselmino: None. A. Mari: None. E. Ferrannini: None. A. Gastaldelli: Advisory Panel; Self; Gilead Sciences, Inc.. Other Relationship; Self; European Foundation for the Study of Diabetes. Consultant; Self; INVENTIVA SA.