Association of nonalcoholic fatty liver disease with insulin resistance

BACKGROUND AND PURPOSE:Nonalcoholic fatty liver disease is frequently assoc iated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some pa tients have normal glucose tolerance or normal weight. We tested the hypoth esis that there is an association between nonalcoholic fatty liver disease and insulin resistance that is independent of diabetes and obesity. SUBJECTS AND METHODS: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, "brig ht liver" on ultrasound scan, and normal glucose tolerance. Indexes of insu lin resistance and secretion were determined using the homeostasis model as sessment method. They were compared with 92 normal subjects who were matche d for age and sex. RESULTS: Patients with nonalcoholic fatty liver disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postlo ad hypoglycemia, and hypertriglyceridemia. Insulin resistance [odds ratio ( OR) = 15 per percent increase, 35% confidence interval (CI): 3.0 to 70], fa sting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/ liter decrease, 95 % CI: 1.6 to 12), and average insulin concentration in response to oral glu cose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were indepe ndently associated with nonalcoholic fatty liver disease. The exclusion of overweight and obese subjects did not change the results. CONCLUSION: Nonalcoholic fatty liver disease is associated with insulin res istance and hyperinsulinemia even in lean subjects with normal glucose tole rance, Genetic factors that reduce insulin sensitivity and increase serum t riglyceride levels may be responsible for its development. Am J Med. 1999;1 07: 450-455. (C) 1999 by Excerpta Medica, Inc.