Nonalcoholic Steatohepatitis (NASH) Significantly Contribute to beta-Cell Function Impairment Independently of Glucose Tolerance Status

ß-cell dysfunction is a strong risk factor for type 2 diabetes (T2D). The liver plays a central role since insulin clearance (ClearIns) is up to 80% of the insulin secretion rate (ISR). ClearIns is reduced with insulin resistance (IR) and in patients with nonalcoholic fatty liver disease (NAFLD) . Our aim was to evaluate if ISR and ß-cell function were decreased in NASH vs. NAFL thus increasing their risk of T2D and the impact of ClearIns and IR. We measured glucose, insulin and c-peptide during a 3h oral glucose tolerance test in 341 subjects with liver biopsy and evaluated ISR (from deconvolution of c-peptide), ClearIns, Matsuda insulin sensitivity index (ISI) and disposition index (DI=ISI∙ΔAUC-I/ΔAUC-G); a low DI indicates a risk to develop T2D. Subjects were grouped according to glucose tolerance, normal (NGT), impaired (IGT) or T2D, and liver histology (noNAFL, NAFL, NASH-Fibrosis F0-F1 and F2-F4). The groups had similar BMI (∼34kg/m2). Severity of NAFLD was associated with increased IR, fasting and postprandial ISR and decreased ClearIns, after adjusting for age and BMI. DI was significantly lower in NASH-F24 in each glucose tolerance group (Figure). Conclusion: Disposition index is reduced in relation to presence and severity of NASH independent of glucose tolerance status supporting an independent role of NASH in the development of T2D. Disclosure L. Vonghia: None. E. Dirinck: None. F. Carli: None. A. Verrijken: None. J. Weyler: None. P. Michielsen: None. T. Vanwolleghem: None. A. Driessen: None. L. Van Gaal: None. S. Francque: None. C. De Block: Advisory Panel; Self; A. Menarini Diagnostics, Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD, Novartis AG, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S. A. Gastaldelli: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Inventiva Pharma, Novo Nordisk Inc. Funding Horizon2020 (634413)