Prospective Study of Serum γ-Glutamyltransferase and Risk of NIDDM
Abstract
OBJECTIVE: Serum gamma-glutamyltransferase (GGT) levels are raised in obese individuals, and a particularly strong association with central obesity has been described. We hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. To test this hypothesis, we examined the association between GGT levels and risk of NIDDM. RESEARCH DESIGN AND METHODS: We carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40-59 years) followed for a mean of 12.8 years (range 11.5-13.0). The men were randomly selected from general practice lists in 24 British towns. Cases of NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records. RESULTS: A total of 194 men developed NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% CI]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3-22.6] vs. 15.3 U/l [15.0-15.6], P < 0.0001). There was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5-12.9) relative to the bottom fifth (trend P < 0.0001). This association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0-11.8], trend P < 0.0001]). CONCLUSIONS: These findings suggest that a raised serum GGT level is an independent risk factor for NIDDM. Serum GGT level may be a simple and reliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance.
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Nonalcoholic fatty liver disease precedes and predicts type 2 diabetes.
“N onalcoholic fatty liver disease (NAFLD) precedes and predicts type 2 diabetes.[1][2][3][4][5][6]”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [3]
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“[26] I.”
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“Accordingly, authors have found that the associations between GGT levels and diabetes or blood pressure have been attenuated on adjustment for known risk factors for diabetes or for plasma insulin levels and have speculated that visceral fat could play a role in the association of GGT with type 2 diabetes [ 2 ,4,27]”
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- Authors
- Perry, I. J., Wannamethee, S. G., & Shaper, A. G.
- Affiliations
- The Royal Free Hospital (GB)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1998-05-01
- Volume
- 21
- Issue
- 5
- Pages
- 732-737
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2146589543
- Cited by
- 319
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 10 · 2019: 1 · 2018: 8 · 2017: 10 · 2016: 14 · 2015: 5 · 2014: 15 · 2013: 13 · 2012: 18
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- 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
- gamma-glutamyl transferase, type 2 diabetes, type 2 diabetes risk, hepatic steatosis, visceral fat, hepatic insulin resistance, biomarkers, alcohol consumption, physical activity, obesity, men
- MeSH terms
- Adult, Alcohol Drinking, Alkaline Phosphatase, Aspartate Aminotransferases, Diabetes Mellitus, Type 2, Follow-Up Studies, gamma-Glutamyltransferase, United Kingdom, Humans, Liver, Male, Middle Aged, Obesity, Predictive Value of Tests, Prospective Studies, Risk Factors, Body Mass Index, Incidence, Multivariate Analysis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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