Low Incretin Effect Is Associated with Longitudinal Decline of Beta-Cell Function and Insulin Sensitivity in Obese Youth

Background: We assessed the longitudinal trajectory of beta-cell function with respect to baseline incretin effect in youth with obesity. Methods: At baseline and two years, youth with obesity and 2-h glucose ≥ 120mg/dL underwent a 3-hour OGTT and isoglycemic intravenous glucose infusion (to quantify the incretin effect) . Participants were stratified into three tertiles based on the baseline incretin effect. The oral minimal model quantified beta cell function (oDI) and insulin sensitivity (SI) . Results: Thirty participants completed the assessments [follow-up: age 18.6±2.4y, 19F; BMI 38.6±7.4 kg/m2, NGT/IGT/T2D 12/17/1]. At 2 years, 2-h glucose improved in the high incretin group (p=0.047) , but was stable in the middle- and low- incretin groups (panel G) . At 2 years, the baseline high-incretin group exhibited a lower 60-min glucose (p=0.026) than the low-incretin group, with similar 120-min glucose (p=0.696) , despite the low-incretin cohort’s relative increase in early insulin secretion (panel D, F) . The low-incretin tertile also exhibited a reduced β cell function (oDI) at follow-up (panel I) (p=0.044) mainly due to lower insulin sensitivity (panel H) (p=0.013) . Conclusion: Low incretin effect is associated with a longitudinal decline of beta cell function and decreased insulin sensitivity, despite greater first-phase insulin secretion. Disclosure A.Galderisi: None. J.O.Lat: None. S.Samuels: None. B.Pierpont: None. M.A.Van name: Research Support; Provention Bio, Inc. N.Santoro: None. S.Caprio: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases/NIH/DHHS (16-004945)