1756-P: ß-Cell Glucose Sensitivity and Intrapancreatic Adipose Tissue as Predictors of Diabetes Onset

Abstract

Several evidences suggest that the functional β cell defects anticipate the onset of hyperglycemia and the reduction of mass. To assess whether the β-cell deterioration corresponds to a loss of β-cell mass, we performed glucose oral tolerance test (OGTT) and hyperglycemic clamp (HC) followed by arginine stimulation, in 16 nondiabetic patients who underwent pancreatoduodenectomy (PD), pre and post-surgery. Based on the post-operative OGTT, the subjects were divided into 3 glucose tolerance groups: normal (NGT, n = 5), altered (IGT, n = 4) or diabetes (DM, n = 7) (8F/8M, 51 ± 15 years). To evaluate β cell function, βcell glucose sensitivity (GS) was calculated during HC, as a ratio between insulin secretion and glucose increase. On surgical pancreas samples, the% of intraparenchymal white adipose tissue (WATi score) was measured. Before surgery, insulin secretion after arginine (AIS) was similar between groups, while GS was lower in IGT and DM compared to NGT subjects (62.9 ± 23.1 and 45.5 ± 11.2 vs. 90.6 ± 18.7 pmol • min-1 • m-2, respectively). After 50% PD, the GS decreased in all patients (p <0.01 for all groups), but the reduction was greater in DM than in patients with IGT and NGT (ΔGS: NGT -0.20 ± 0, 19 vs. IGT -0.27 ± 0.11 vs. DM 0.37 ± 0.08, p <0.003). A similar reduction was observed in ΔAIS (NGT -0.38 ± 0.13 vs. IGT -0.76 ± 0.06 vs. DM -0.90 ± 0.04; p <0.01) and in the second phase of insulin secretion. WAT score was significantly higher in IGT and DM than in NGT (WATi score IGT 37.75 ± 11.07%, DM 44.46 ± 31.83%, NGT 5.8 ± 2.35%, p <0.01 and p <0.05 respectively). The loss of GS is the most sensitive predictive parameter of diabetes onset after a 50% reduction in mass. The accumulation of WATi could in turn predict the loss of GS and represent a new potential target for the preservation of the function. Disclosure F. Cinti: None. T. Mezza: None. C. Cefalo: None. G. Sorice: None. S. Moffa: None. I. Severi: None. S. Cinti: None. A. Giaccari: Advisory Panel; Self; Sanofi. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp., Sanofi.