Mechanisms for increased risk of diabetes in chronic liver diseases
- 1 October 2020
- journal article
- research article
- Published by Wiley in Liver International
- Vol. 40 (10), 2489-2499
- https://doi.org/10.1111/liv.14556
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 (Delta AUC-I/Delta AUC-G) and disposition-index (DI = OGIS center dot Delta AUC-I/Delta AUC-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 (Delta AUC-I/Delta AUC-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, allP < .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.Funding Information
- H2020 Health (634413)
- H2020 Marie Skłodowska-Curie Actions (691042, 722619, 734719)
This publication has 53 references indexed in Scilit:
- Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th editionDiabetes Research and Clinical Practice, 2019
- Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysisDiabetes Care, 2018
- Global burden of NAFLD and NASH: trends, predictions, risk factors and preventionNature Reviews Gastroenterology & Hepatology, 2018
- Extrahepatic Morbidity and Mortality of Chronic Hepatitis CGastroenterology, 2015
- Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart DiseaseNutrients, 2013
- Longitudinal Effects of MRI-Measured Hepatic Steatosis on Biomarkers of Glucose Homeostasis and Hepatic Apoptosis in Obese YouthDiabetes Care, 2012
- Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis CHepatology, 2009
- Hepatitis C infection and risk of diabetes: A systematic review and meta-analysisJournal of Hepatology, 2008
- Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) studyDiabetologia, 2003
- HCV and diabetes mellitus: evidence for a negative associationThe American Journal of Gastroenterology, 1998