Alanine transaminase has opposite associations with death from diabetes and ischemic heart disease in NHANES III.

PURPOSE: Diabetes increases the risk of ischemic heart disease (IHD). Stringent control of diabetes does not reliably reduce cardiovascular events. Some global regions, such as East Asia, have low mortality rates from IHD and high rates of diabetes. We hypothesized that some aspects of liver function might underlie this paradox.

METHODS

We used multivariable proportional hazards regression in 16,865 adults from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) followed until December 31, 2006, to assess the adjusted associations of gender-specific tertiles of alanine transaminase (ALT), as a marker of hepatocellular damage, and bilirubin (BIL), as a marker of other aspects of liver function, with death from diabetes (n = 132), IHD related to diabetes (n = 153), and IHD unrelated to diabetes (n = 921).

RESULTS

ALT was positively associated with death from diabetes (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.19-3.98 for high compared with low ALT tertile) and IHD related to diabetes (HR, 2.14; 95% CI, 1.07-4.31), but negatively associated with IHD unrelated to diabetes (HR, 0.76; 95% CI, 0.58-0.98) adjusted for age, gender, education, race/ethnicity, smoking, and alcohol use. BIL had no such associations.

CONCLUSIONS

ALT may be a marker of an underlying etiology relating to the paradoxical associations of diabetes and IHD at a population level.