TY - JOUR
T1 - Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes
T2 - analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study
AU - Williams, Kathryn H.
AU - Sullivan, David R.
AU - Nicholson, Geoffrey C.
AU - George, Jacob
AU - Jenkins, Alicia J.
AU - Januszewski, Andrzej S.
AU - Gebski, Val J.
AU - Manning, Patrick
AU - Tan, Yong Mong
AU - Donoghoe, Mark W.
AU - Ehnholm, Christian
AU - Young, Simon
AU - O'Brien, Richard
AU - Buizen, Luke
AU - Twigg, Stephen M.
AU - Keech, Anthony C.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - mortality
KW - alanine aminotransferase
KW - γ-Glutamyl transferase
KW - diabetes mellitus
KW - non-alcoholic fatty liver disease
UR - http://www.scopus.com/inward/record.url?scp=84960421208&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/nhmrc/1037786
U2 - 10.1016/j.metabol.2015.12.008
DO - 10.1016/j.metabol.2015.12.008
M3 - Article
C2 - 27085785
AN - SCOPUS:84960421208
SN - 0026-0495
VL - 65
SP - 783
EP - 793
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 5
ER -