Hyperinsulinemia and the Development of Nonalcoholic Fatty Liver Disease in Nondiabetic Adults

BACKGROUND: Insulin resistance is known to be the most important pathogenic factor in the development of nonalcoholic fatty liver disease. We performed a prospective study to analyze the associations of baseline and changes in fasting insulin levels with future development of nonalcoholic fatty liver disease in nondiabetic adults over a 5-year period. METHODS: This study was performed in 4954 subjects who did not have diabetes or nonalcoholic fatty liver disease and who participated in a health checkup program in both 2003 and 2008. The presence of nonalcoholic fatty liver disease was defined by ultrasonographic examination. Subjects were divided into 4 groups according to the baseline quartiles of fasting insulin and dichotomized fasting insulin levels at baseline and after 5 years: low-low, low-high, high-low, high-high. RESULTS: After 5 years, 644 subjects (13%) developed nonalcoholic fatty liver disease. The odds ratio (OR) for development of nonalcoholic fatty liver disease increased as the quartiles of the baseline fasting insulin levels increased from the first to the fourth quartile (1.00 vs. 0.99, 1.44, 1.65, respectively). The OR for nonalcoholic fatty liver disease was 2.5-fold higher in the high-high group and 1.6-fold higher in the low-high group compared with that of the low-low group. The OR for nonalcoholic fatty liver disease increased as the quartile of changes in fasting insulin level over the 5-year period increased. CONCLUSION: High baseline and continuously increasing fasting insulin levels were the independent determinants for future development of nonalcoholic fatty liver disease during a 5-year follow-up in nondiabetic healthy adults. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 69-76