Cumulative Exposure to High gamma-Glutamyl Transferase Level and Risk of Diabetes: A Nationwide Population-Based Study

Abstract

Background: Elevated gamma-glutamyl transferase (gamma-GTP) level is associated with metabolic syndrome, impaired glucose tolerance, and insulin resistance, which are risk factors for type 2 diabetes. We aimed to investigate the association of cumulative exposure to high gamma-GTP level with risk of diabetes. Methods: Using nationally representative data from the Korean National Health Insurance system, 346,206 people who were free of diabetes and who underwent 5 consecutive health examinations from 2005 to 2009 were followed to the end of 2018. High gamma-GTP level was defined as those in the highest quartile, and the number of exposures to high gamma-GTP level ranged from 0 to 5. Hazard ratio (HR) and 95% confidence interval (CI) for diabetes were analyzed using the multivariable Cox proportional-hazards model. Results: The mean follow-up duration was 9.2 +/- 1.0 years, during which 15,183 (4.4%) patients developed diabetes. There was a linear increase in the incidence rate and the risk of diabetes with cumulative exposure to high gamma-GTP level. After adjusting for possible confounders, the HR of diabetes in subjects with five consecutive high gamma-GTP levels were 2.60 (95% CI, 2.47 to 2.73) in men and 3.05 (95% CI, 2.73 to 3.41) in women compared with those who never had a high gamma-GTP level. Similar results were observed in various subgroup and sensitivity analyses. Conclusion: There was a linear relationship between cumulative exposure to high gamma-GTP level and risk of diabetes. Monitoring and lowering gamma-GTP level should be considered for prevention of diabetes in the general population.