Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study.
OBJECTIVE
To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes.


METHODS
From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT).


RESULTS
At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations.


CONCLUSIONS
Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.
Department of Internal Medicine, University of Pisa School of Medicine, Via Roma, 67, 56126 Pisa, Italy.
Monica
M
Nannipieri
Clicerio
C
Gonzales
Simona
S
Baldi
Rosalinda
R
Posadas
Ken
K
Williams
Steven M
SM
Haffner
Michael P
MP
Stern
Ele
E
Ferrannini
D000410:Alanine Transaminase / Q000097:blood*; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood*; D003920:Diabetes Mellitus / Q000201:enzymology / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology / Q000453:epidemiology*; D008800:Mexico / Q000453:epidemiology; D011237:Predictive Value of Tests; D005723:gamma-Glutamyltransferase / Q000097:blood
D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase