Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection.
OBJECTIVE
Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance.


METHODS
Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated.


RESULTS
Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis.


CONCLUSIONS
Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.
Maeno
Tadashi
T
Division of Gastroenterology, Department of Internal Medicine and Research Center for Infectious Diseases, Aichi Medical University School of Medicine, Aichi, Japan.
Okumura
Akihiko
A
Ishikawa
Tetsuya
T
Kato
Koichi
K
Sakakibara
Fumihiko
F
Sato
Ken
K
Ayada
Minoru
M
Hotta
Naoki
N
Tagaya
Tsuneaki
T
Fukuzawa
Yoshitaka
Y
Kakumu
Shinichi
S
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D008954:Models, Biological
D000410:Alanine Transaminase; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin