Glycemic Variability Is an Independent Predictive Factor for Development of Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease

Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) often have metabolic disorders including insulin resistance and type 2 diabetes mellitus (T2DM). We clarified the predictive factors in glucose metabolism for progression of hepatic fibrosis in patients with NAFLD by the 75-g oral glucose tolerance test (75gOGTT) and a continuous glucose monitoring system (CGMS). One hundred sixty-nine patients (68 female and 101 male patients) with biopsy-proven NAFLD with performance with 75gOGTT were enrolled and divided into four groups according to the stage of hepatic fibrosis (F0-3). The proportion of patients with T2DM significantly gradually increased, HbA1c and the homeostasis model assessment of insulin resistance were significantly elevated, and 1,5-anhydroglucitol (1,5-AG) was remarkably decreased with the progression of fibrosis. In the 75gOGTT, both plasma glucose and insulin secretion were remarkably increased with the progression of fibrosis. The only factor significantly associated with advanced fibrosis was 1,5-AG (P = 0.008) as determined by multivariate logistic regression analysis. We next evaluated the changes in blood glucose during 24 hours by monitoring with the CGMS to confirm the relationship between glycemic variability and progression of fibrosis. Variability of median glucose, standard deviation of median glucose (P = 0.0022), maximum blood glucose (P = 0.0019), and Delta Min-max blood glucose (P = 0.0029) were remarkably higher in severe fibrosis than in mild fibrosis. Conclusion: Hyperinsulinemia and hyperglycemia, especially glycemic variability, are important predictive factors in glucose impairment for the progression of hepatic fibrosis in NAFLD.