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Cited by 717Liver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsDiet, Metabolism, and Disease

High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

Vozarova, Barbora, Stefan, Norbert, Lindsay, Robert S., Saremi, Aramesh, Pratley, Richard E., Bogardus, Clifton, Tataranni, P. Antonio·2002·Diabetes
DOI 10.2337/diabetes.51.6.1889
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Abstract

It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO] during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge). Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, - 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs. 10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02], but not AST or GGT, predicted diabetes. Elevated ALT at baseline was associated prospectively with an increase in HGO (r = 0.21, P = 0.001) but not with changes in M or AIR (both P = 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes.

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Authors
Vozarova, B., Stefan, N., Lindsay, R. S., Saremi, A., Pratley, R. E., Bogardus, C., & Tataranni, P. A.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2002-06-01
Volume
51
Issue
6
Pages
1889-1895
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.51.6.1889
OpenAlex
W2158468809
Cited by
717
References
28
Citations by year
2026: 7 · 2025: 15 · 2024: 21 · 2023: 36 · 2022: 23 · 2021: 36 · 2020: 35 · 2019: 30 · 2018: 29 · 2017: 38 · 2016: 39 · 2015: 46 · 2014: 48 · 2013: 35 · 2012: 30
FWCI
13.32
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
alanine aminotransferase, type 2 diabetes, hepatic insulin sensitivity, hepatic glucose production, insulin secretion, acute insulin response, liver enzymes, gamma-glutamyl transferase, aspartate aminotransferase, Pima Indians, fat mass, hyperinsulinemic-euglycemic clamp, diabetes risk prediction, liver dysfunction, prediabetes, insulin resistance
MeSH terms
Adipose Tissue, Adolescent, Adult, Alanine Transaminase, Aspartate Aminotransferases, Body Composition, Cross-Sectional Studies, Diabetes Mellitus, Type 2, gamma-Glutamyltransferase, Glucose Tolerance Test, Humans, Indians, North American, Insulin, Insulin Resistance, Liver, Longitudinal Studies, Middle Aged, Obesity, Prospective Studies, Glucose Clamp Technique

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