Nonalcoholic fatty liver disease is frequently associated with type 2 diabetes mellitus,
obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal
weight. We tested the hypothesis that there is an association between nonalcoholic
fatty liver disease and insulin resistance that is independent of diabetes and obesity.
We measured anthropometric and metabolic variables in 46 patients with chronically
elevated serum aminotransferase levels, "bright liver" on ultrasound scan, and normal
glucose tolerance. Indexes of insulin resistance and secretion were determined using
the homeostasis model assessment method. They were compared with 92 normal subjects
who were matched for age and sex.
Patients with nonalcoholic fatty liver disease were characterized by fasting and glucose-induced
hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia.
Insulin resistance [odds ratio (OR) = 15 per percent increase, 95% confidence interval
(CI): 3.0 to 70], fasting 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 glucose
(OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated
with nonalcoholic fatty liver disease. The exclusion of overweight and obese subjects
did not change the results.
Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia
even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin
sensitivity and increase serum triglyceride levels may be responsible for its development.