Liver Enzymes, the Metabolic Syndrome, and Incident Diabetes

The Mexico City Diabetes Study

  1. Monica Nannipieri, MD1,
  2. Clicerio Gonzales, MD2,
  3. Simona Baldi, PHD1,
  4. Rosalinda Posadas, PHD1,
  5. Ken Williams, MSC3,
  6. Steven M. Haffner, MD3,
  7. Michael P. Stern, MD3 and
  8. Ele Ferrannini, MD1
  1. 1Metabolism Unit, Department of Internal Medicine and C.N.R. Institute of Clinical Physiology, University of Pisa School of Medicine, Pisa, Italy
  2. 2American British Cowdray Hospital and Endocrinology and Metabolism Service, Specialty Hospital of the National Medical Center, Mexican Social Security Institute, Mexico City, Mexico
  3. 3Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
  1. Address correspondence and reprint requests to Ele Ferrannini, MD, Department of Internal Medicine, Via Roma, 67, 56126 Pisa, Italy. E-mail: ferranni{at}


OBJECTIVE—To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes.

RESEARCH DESIGN AND METHODS—From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were ≤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.


  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted April 14, 2005.
    • Received September 23, 2004.
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