Clinical Studies
Association of nonalcoholic fatty liver disease with insulin resistance

https://doi.org/10.1016/S0002-9343(99)00271-5Get rights and content

Abstract

BACKGROUND AND PURPOSE: 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.

SUBJECTS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Section snippets

Patients

Since September 1997, all outpatients who visited our Department of Liver and Metabolic Disease for chronically elevated serum aminotransferase levels were screened for hepatitis B, C, and Epstein-Barr virus infection, nonorgan-specific autoantibodies, and hereditary defects (α1-antitrypsin deficiency and iron and copper storage diseases). Alcohol consumption was assessed by detailed history and laboratory markers (serum γ-glutamyl transpeptidase levels and mean corpuscular volume of red blood

Results

Among the 46 patients with nonalcoholic fatty liver disease (Table), 20 (43%) were overweight (body mass index from 25 to 30 kg/m2) and 13 were frankly obese (body mass index greater than 30 kg/m2). Of the 92 control subjects, 28 (30%) had a body mass index exceeding 25 kg/m2, but none was obese. Fat was mainly distributed in the splanchnic area. Among the patients, the mean waist circumference was 95 ± 14 cm in men and 87 ± 11 cm in women, significantly greater than in the controls [men 84 ±

Discussion

The present study demonstrates that insulin resistance, elevated serum triglyceride levels, hyperinsulinemia, and lower glucose levels after a glucose load are associated with nonalcoholic fatty liver disease, irrespective of body weight, body mass index, fat distribution, and glucose tolerance. The diagnosis of nonalcoholic fatty liver disease was based on exclusion of known etiologic factors responsible for liver disease (viral, genetic, autoimmune) and on ultrasound examinations, but was not

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