Hepatic enzymes, the metabolic syndrome, and the risk of type 2 diabetes in older men.
OBJECTIVE
We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk.


METHODS
We conducted a prospective study of 3,500 nondiabetic men aged 60-79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases.


RESULTS
In cross-sectional analyses, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47-5.02]; GGT: 3.68 [1.68-8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01-3.60] and 2.69 [1.21-5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk.


CONCLUSIONS
Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.
Wannamethee
Sasiwarang Goya
SG
Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, U.K. goya@pcps.ucl.ac.uk
Shaper
Andrew Gerald
AG
Lennon
Lucy
L
Whincup
Peter H
PH
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D003925:Diabetic Angiopathies / Q000453:epidemiology; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology*; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase