Analysis of factors influencing glucose tolerance in Japanese patients with non-alcoholic fatty liver disease.

BACKGROUND: While the association of the prevalence of non-alcoholic fatty liver disease (NAFLD) with impaired glucose metabolism has been reported, the factors influencing glucose tolerance in NAFLD remain to be clarified.

METHODS: Glucose tolerance of 131 Japanese patients diagnosed as NAFLD by histological findings of liver biopsy specimen was examined using 75 g-OGTT. According to Matteoni's classification, patients were divided to 4 groups [M1 ~ 4, M1, 2: non-alcoholic fatty liver (NAFL); and M3, 4: non-alcoholic steatohepatitis (NASH)]. Based on the OGTT data, insulinogenic index (IGI) and QUICKI were calculated as indices of insulin secretion and insulin sensitivity, respectively. Plasma glucose 120 min after glucose loading (G120 ) was used as the index for glucose intolerance.

RESULTS: Stepwise multiple regression analysis using G120 as a dependent variable and loge -IGI, QUICKI, sex, BMI, age, NAFL/NASH as independent variables revealed that loge -IGI (β = -0.595) and QUICKI (β = -0.323) are significant factors predicting glucose intolerance (R2  = 0.403), indicating an important role of insulin secretion in glucose tolerance. These findings accord with glucose intolerance as high as 89.7% in patients with impaired insulin secretion defined by ≤43.2 pmol/mmol (40 μU/mg) IGI. Stepwise multiple regression analysis using QUICKI as a dependent variable and NAFL/NAFLD, sex, BMI, and age as independent variables revealed that BMI (β = -0.469) and NAFL/NAFLD (β = -0.204) are significant factors predicting insulin sensitivity (R2  = 0.248).

CONCLUSION: Impairment of insulin secretion is the most important factor to predict glucose intolerance in NAFLD; severity of histological findings is associated with insulin sensitivity independent of adiposity in NAFLD.