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Mechanisms for increased risk of diabetes in chronic liver diseases
Author(s) -
SvegliatiBaroni Gianluca,
Gaggini Melania,
Carli Fabrizia,
Barbieri Chiara,
Cucco Monica,
Younes Ramy,
Rosso Chiara,
Bugianesi Elisabetta,
Gastaldelli Amalia
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14556
Subject(s) - medicine , insulin resistance , steatosis , fatty liver , type 2 diabetes , gastroenterology , liver biopsy , nonalcoholic fatty liver disease , endocrinology , homeostatic model assessment , diabetes mellitus , insulin , chronic liver disease , liver disease , disease , biopsy , cirrhosis
Abstract Objective Patients with chronic liver disease (CLD), both non‐alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), are at high risk of diabetes (T2D), but mechanisms are still unknown. Muscle/liver insulin resistance (IR) and pancreatic dysfunction are the major metabolic defects leading to T2D. However, if the risk of T2D in CLD patients is because of reduced insulin response and/or to IR, and the impact of liver histology has not been investigated. Design We studied 220 non‐T2D patients with chronic liver disease (129 NAFLD, BMI = 27.3 kg/m 2 ; 91 CHC, BMI = 25.0 kg/m 2 ) that received a 75‐gram oral glucose tolerance test (OGTT) with the measurement of glucose and insulin concentrations for 2 hours, glucose tolerance (NGT vs IGT) and liver biopsy. The results were compared to 26 controls (CT‐NGT, BMI = 25.6 kg/m 2 ). We evaluated peripheral insulin sensitivity (OGIS), OGTT‐insulin response (ΔAUC‐I/ΔAUC‐G) and disposition‐index (DI = OGIS∙ΔAUC‐I/ΔAUC‐G) for the risk to develop T2D. Results NAFLD had increased muscle IR (associated to NASH, steatosis and fibrosis), higher than in CHC or CT‐NGT (OGIS = 8.9 vs 11.3 and 10.5 mL/min kg, P < .0001). In NAFLD, OGTT‐insulin response (ΔAUC‐I/ΔAUC‐G) was the highest while it was significantly decreased in CHC (2.2 vs 1.1 and 1.6, NAFLD vs. CHC and CT‐NGT, P < .005). The highest T2D risk (low DI) was observed in CHC‐IGT (7.5), CHC‐NGT (13.5) and NAFLD‐IGT (10.8) vs CT‐NGT (14.9, all P < .0001), but not in NAFL‐NGT or NASH‐NGT. Conclusion We observed an increased T2D risk in NAFLD‐IGT, CHC‐IGT and CHC‐NGT mainly because of reduced OGTT‐insulin response, while insulin response in NAFLD‐NGT compensates the IR thus maintaining normal glycaemia.