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 (G(120)) was used as the index for glucose intolerance. RESULTS: Stepwise multiple regression analysis using G(120) as a dependent variable and log(e)-IGI, QUICKI, sex, BMI, age, NAFL/NASH as independent variables revealed that log(e)-IGI (β = −0.595) and QUICKI (β = −0.323) are significant factors predicting glucose intolerance (R(2) = 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 (R(2) = 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.