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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Clinical Diabetes

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1552044

Nonlinear Association Between Gamma-Glutamyl Transferase to High-Density Lipoprotein Cholesterol Ratio and Risk of Progression from Normoglycemia to Prediabetes:a 5-year cohort study

Provisionally accepted
Chuang  GaoChuang Gao1Cailing  YuCailing Yu1Peijie  ShiPeijie Shi1Dehong  LiuDehong Liu2Qiming  LiQiming Li2Yong  HanYong Han2*
  • 1Shenzhen Dapeng New District Kuichong People's Hospital, shenzhen, China
  • 2Shenzhen Second People's Hospital, Shenzhen, Guangdong Province, China

The final, formatted version of the article will be published soon.

Objective: Current research on the association between the Gamma-glutamyl transferase to highdensity lipoprotein ratio (GHR) and the risk of prediabetes (pre-DM) remains scarce. This study aims to explore the potential link between GHR and the risk of progression from normoglycemia to pre-DM.Methods: This retrospective cohort study included 8,168 individuals who voluntarily underwent health examinations at Shenzhen Dapeng New District Kuichong People's Hospital between January 2018 and December 2023. To assess the association between GHR and the risk of developing pre-DM, Cox proportional hazards regression models were employed. Cox proportional hazards regression model with cubic spline function was further utilized to investigate potential nonlinear association. Moreover, a competing risk Cox proportional hazards model was applied to account for the progression from normoglycemia to diabetes (DM) as a competing event in the progression from normoglycemia to pre-DM. Subgroup analyses and multiple sensitivity analyses were also performed to ensure the robustness of the findings.Results: Following multivariate adjustment, elevated GHR demonstrated a significant correlation with increased risk of progression from normoglycemia to pre-DM, showing a hazard ratio(HR) of 1.061 (95% CI: 1.028-1.095) for each 5-unit increment. A nonlinear relationship between them was identified, with an inflection point at a GHR value of 24.37. On the left side of the inflection point, the HR for the association between GHR (per 5-unit increase) and pre-DM risk was 1.394 (95% CI: 1.197, 1.623). Furthermore, the competing risk model revealed an HR of 1.05 (95% CI: 4 1.02, 1.09) for the association between GHR (per 5-unit increase) and pre-DM risk. Multiple sensitivity analyses confirmed the stability and reliability of these results.Conclusion: This study demonstrates that elevated GHR exhibits both a positive and nonlinear relationship with the risk of progression from normoglycemia to pre-DM among Chinese adults.Maintaining GHR values below the threshold of 24.37, coupled with further reduction efforts, may serve as an effective strategy to minimize pre-DM risk.

Keywords: prediabetes, γ-glutamyl transferase, γ-glutamyl transferase to high-density lipoprotein ratio, nonlinearity, Competing risk model

Received: 27 Dec 2024; Accepted: 23 Jun 2025.

Copyright: © 2025 Gao, Yu, Shi, Liu, Li and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yong Han, Shenzhen Second People's Hospital, Shenzhen, Guangdong Province, China

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