Chronic hepatitis C virus infection without cirrhosis induces insulin resistance in patients with alpha-thalassaemia major.

Abstract

The aim of this study was to investigate the cause of increased incidence of impaired glucose tolerance and diabetes mellitus in patients with alpha-thalassaemia major and chronic hepatitis C virus (HCV) infection without cirrhosis of the liver. The study included 28 alpha-thalassaemic multi-transfused patients (14 females and 14 males; age, 25.7 +/- 6.3 years) with normal fasting glucose levels. Sixteen were seropositive for HCV and they had biopsy proven chronic hepatitis C without cirrhosis. An oral glucose tolerance test (OGTT) was performed. Glucose, insulin and C-peptide levels were measured every 30 min for 2 h. Fasting insulin resistance index (FIRI) was calculated according to the formula: FIRI = (fasting glucose x fasting insulin)/25. All patients had a normal OGTT except for two HCV positive and two HCV negative patients who had impaired glucose tolerance. HCV positive patients had higher fasting insulin levels (P = 0.02), higher fasting insulin/fasting glucose ratio (P = 0.017) and higher FIRI (P = 0.016) than HCV negative patients. During the OGTT, peak insulin levels occurred at 30 min in HCV negative patients but at 60 min in HCV positive. HCV infected patients had higher mean value of insulin at 60 (P = 0.017), 90 (P = 0.04), and 120 min (P = 0.04), and higher mean increment above basal at 60 (P = 0.015), 90 (P = 0.018) and 120 min (P = 0.05). The area under the curve (AUC) of insulin was also greater in HCV positive patients as compared to HCV negative (P = 0.04), although the AUC of glucose and the glucose levels at all time points of the OGTT were similar in both groups. The findings of this study show that alpha-thalassaemic patients with HCV infection without liver cirrhosis are more insulin resistant and have delayed insulin secretion compared to HCV negative alpha-thalassaemic patients. These changes in insulin action and secretion are evident before the development of impaired glucose tolerance and may explain the higher prevalence of diabetes mellitus in this group.