NAFLD as a Risk Factor for the Development of Diabetes and the Metabolic Syndrome: An Eleven-Year Follow-up Study

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) uncommonly results in cirrhosis and liver-related death; however, its impact on the development of metabolic complications remains unclear. We sought to determine whether NAFLD with elevated aminotransaminase (ALT) levels was a risk factor for incident diabetes or the metabolic syndrome (MS) over an 11-year period. METHODS: Adult residents of Busselton, Western Australia underwent assessment in 1994-1995 as part of the Busselton Health Survey. NAFLD was diagnosed on the basis of a raised ALT (> 40 IU/l) after the exclusion of alcohol, viral, metabolic, and autoimmune liver disease. NAFLD and non-NAFLD subjects were reassessed in 2005 for liver complications, diabetes, and the MS. RESULTS: A total of 358 subjects, 68% male (109 NAFLD, 249 non-NAFLD), mean age (s.d.) 59.9 (11.6) years, attended follow-up 11.1 years after the initial assessment. After excluding subjects with diabetes at baseline, those with NAFLD were more likely to have developed diabetes on follow-up (20/106, 18.9% vs. 15/246, 6.1%; P < 0.001). After excluding subjects with MS at baseline, those with NAFLD were more likely to have developed MS at follow-up (27/81, 33.3% vs. 51/226, 22.6%; P = 0.056). However, in multivariate logistic regression models, NAFLD was no longer a significant independent predictor of the development of diabetes or MS after adjusting for baseline waist circumference, hypertension, and insulin resistance. None of the subjects developed liver complications. CONCLUSIONS: Subjects with NAFLD and elevated ALT levels are at an increased risk of developing diabetes and the MS. This may be because of the presence of associated metabolic risk factors.