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

Williams, Kathryn H., Sullivan, David R., Nicholson, Geoffrey C., George, Jacob, Jenkins, Alicia J., Januszewski, Andrzej S., Gebski, Val J., Manning, Patrick, Tan, Yong Mong, Donoghoe, Mark W., Ehnholm, Christian, Young, Simon, O'Brien, Richard, Buizen, Luke, Twigg, Stephen M. and Keech, Anthony C. (2016) 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. Metabolism: Clinical and Experimental, 65 5: 783-793. doi:10.1016/j.metabol.2015.12.008


Author Williams, Kathryn H.
Sullivan, David R.
Nicholson, Geoffrey C.
George, Jacob
Jenkins, Alicia J.
Januszewski, Andrzej S.
Gebski, Val J.
Manning, Patrick
Tan, Yong Mong
Donoghoe, Mark W.
Ehnholm, Christian
Young, Simon
O'Brien, Richard
Buizen, Luke
Twigg, Stephen M.
Keech, Anthony C.
Title 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
Journal name Metabolism: Clinical and Experimental   Check publisher's open access policy
ISSN 1532-8600
0026-0495
Publication date 2016-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.metabol.2015.12.008
Open Access Status Not Open Access
Volume 65
Issue 5
Start page 783
End page 793
Total pages 11
Place of publication Maryland Heights, MO United States
Publisher W.B. Saunders
Collection year 2016
Language eng
Formatted 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.
Keyword Mortality
Alanine aminotransferase
γ-Glutamyl transferase
Non-alcoholic fatty liver disease
Diabetes mellitus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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