title: High fasting insulin concentrations may be a pivotal predictor for the severity of hepatic fibrosis beyond the glycemic status in non-alcoholic fatty liver disease patients before development of diabetes mellitus.
abstract: BACKGROUND
  Insulin resistance and type 2 diabetes mellitus (T2DM) contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, the relationship between glucose metabolic factors and the histological severity in NAFLD patients before development of T2DM is not well known.
  
  
  METHODS
  In 103 biopsy-proven NAFLD patients (68 men and 35 women) with hemoglobin A1c of <6.5% and fasting blood glucose of <126 mg/dL, we investigated whether glucose metabolic factors influenced the severity of hepatic fibrosis without prior known T2DM.
  
  
  RESULTS
  Female gender, age, serum aspartate aminotransferase, the aspartate aminotransferase/alanine aminotransferase ratio, fasting immunoreactive insulin (f-IRI), homeostasis model assessment - insulin resistance, hemoglobin A1c, hyaluronic acid, and type IV collagen 7 s were significantly higher, and 1,5-anhydroglucitol was significantly lower, in the fibrosis stage F3 group than in the F0-2 group. Multiple logistic regression analysis showed that only f-IRI (P = 0.006; odds ratio, 1.15151; 95% confidence interval, 1.04198-1.27254) was significantly indicated as a predictive factor for F3. As determined by both forward and backward stepwise selection analyses to optimize the model, f-IRI (P = 0001; odds ratio, 1.16788) remained an independent predictive factor for F3. To discriminate the F3 group from the F0-2 group, the area under the receiver operating characteristic curves showed that fasting insulin was 0.7219, and the best cut-off value of f-IRI was 13.2 μU/mL in the receiver operating characteristic curve analysis.
  
  
  CONCLUSIONS
  High fasting insulin concentrations may be a pivotal glucose metabolic predictor for the severity of hepatic fibrosis beyond the glycemic status in NAFLD patients before development of T2DM.
authors: Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors: Kosei
authors: K
authors: Masuda
authors: Department of Environmental Medicine, Kochi Medical School, Kochi, Japan.
authors: Shuhei
authors: S
authors: Noguchi
authors: Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors: Masafumi
authors: M
authors: Ono
authors: Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors: Tsunehiro
authors: T
authors: Ochi
authors: Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors: Kensuke
authors: K
authors: Munekage
authors: Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors: Nobuto
authors: N
authors: Okamoto
authors: Department of Environmental Medicine, Kochi Medical School, Kochi, Japan.
authors: Narufumi
authors: N
authors: Suganuma
authors: Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors: Toshiji
authors: T
authors: Saibara
keywords: NAFLD; fasting insulin; hepatic fibrosis; type 2 diabetes mellitus