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Mechanisms for increased risk of diabetes in chronic liver diseases
- Source :
- Liver International, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2019
-
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/m2 ; 91 CHC, BMI = 25.0 kg/m2 ) 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/m2 ). 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.
- Subjects :
- Blood Glucose
endocrine system
medicine.medical_specialty
endocrine system diseases
medicine.medical_treatment
Glucose Tolerance Test
Humans
Insulin
Diabetes Mellitus, Type 2
Insulin Resistance
Non-alcoholic Fatty Liver Disease
Chronic liver disease
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Diabetes mellitus
Internal medicine
medicine
Diabetes Mellitus
Glucose tolerance test
Hepatology
medicine.diagnostic_test
business.industry
Fatty liver
nutritional and metabolic diseases
medicine.disease
3. Good health
030220 oncology & carcinogenesis
Liver biopsy
030211 gastroenterology & hepatology
Steatosis
business
hormones, hormone substitutes, and hormone antagonists
Type 2
Subjects
Details
- ISSN :
- 14783231
- Volume :
- 40
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Liver international : official journal of the International Association for the Study of the LiverREFERENCES
- Accession number :
- edsair.doi.dedup.....ff55a753c4aef2cbba6553c947dc2822