Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Kathryn H. Williams, David R. Sullivan, Geoffrey C. Nicholson, Jacob George, Alicia J. Jenkins, Andrzej S. Januszewski, Val J. Gebski, Patrick Manning, Yong Mong Tan, Mark W. Donoghoe, Christian Ehnholm, Simon Young, Richard O'Brien, Luke Buizen, Stephen M. Twigg, Anthony C. Keech*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Aims Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5 years. Results Over 5 years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2 U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p < 0.001. Conversely, GGT > 70 U/L, compared with GGT ≤ 70 U/L, had HR 1.82 (1.48-2.24), p < 0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT > 70 U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. Conclusions As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

Original languageEnglish
Pages (from-to)783-793
Number of pages11
JournalMetabolism: Clinical and Experimental
Volume65
Issue number5
DOIs
Publication statusPublished - 1 May 2016
Externally publishedYes

Keywords

  • mortality
  • alanine aminotransferase
  • γ-Glutamyl transferase
  • diabetes mellitus
  • non-alcoholic fatty liver disease

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