2295-PUB: Impaired First-Phase Insulin Secretion Predicts the Development of Hyperglycemia in a Human Model of Acute Beta-Cell Mass Reduction

β-cell functional defects temporally anticipate (and eventually cause) the subsequent development of hyperglycemia, whereas a significant reduction (∼50%) of beta-cell mass is observed at diagnosis of T2D. To further investigate the relative role of beta-cell mass reduction/dysfunction in the development of T2D, we performed, pre- and post-surgery, oral glucose tolerance tests (OGTT) and hyperglycemic clamps (HC), followed by arginine stimulation and mixed meal test (MMT), in 39 patients undergoing pancreatoduodenectomy (PD), as model of acute mass reduction. Based on post-surgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal (NGT, n=11), impaired (IGT, n=10) or diabetic (DM, n=18) (23 F/16 M, 63±13.7 yrs, BMI 23.9±4.5 kg/m2). To evaluate β-cell function, β-cell glucose sensitivity (GS) was calculated during HC, MMT e OGTT as the ratio of insulin secretion (IS) and glucose increments. Comparison among the 3 groups revealed that PD had a significantly different effect on time-dependent change of glucose and insulin levels during all tests (P Disclosure T. Mezza: None. P. Ferraro: None. G. Di Giuseppe: None. C. Cefalo: None. S. Moffa: None. G. Quero: None. F. Cinti: None. F. Impronta: None. U. Capece: None. S. Alfieri: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. A. Giaccari: Speaker’s Bureau; Self; Amgen, AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi-Aventis.