Alanine aminotransferase and mortality in patients with type 2 diabetes ( ZODIAC ‐38)

Combined data suggest a bimodal association of alanine aminotransferase ( ALT ) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all‐cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. Design A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care ( ZODIAC ) study. Cox regression analyses were performed to determine the associations of log 2 ‐transformed baseline ALT with all‐cause, cardiovascular and noncardiovascular mortality. Results In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8–16) U/L. During median follow‐up for 11·1 (6·1–14·0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all‐cause mortality (hazard ratio [ HR ] 0·81; 95% confidence interval [ CI ] 0·72–0·92), independently of potential confounders. This was less attributable to cardiovascular mortality ( HR 0·87; 95% CI 0·72–1·05), than to noncardiovascular mortality ( HR 0·77; 95% CI 0·65–0·90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all‐cause mortality was present with increasing risk for levels of ALT above normal ( P  =   0·003). Discussion In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all‐cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT , while risk again starts to increase when levels are above normal.