NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study.
OBJECTIVE
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.
Adams
Leon A
LA
School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia. leon.adams@uwa.edu.au
Waters
Oliver R
OR
Knuiman
Matthew W
MW
Elliott
Robert R
RR
Olynyk
John K
JK
D000410:Alanine Transaminase / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D005234:Fatty Liver / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D011159:Population Surveillance; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014904:Western Australia / Q000453:epidemiology
D000410:Alanine Transaminase