AUTHOR=Bi Yaru , Yang Shuo , Liu Yanjing , Cao Lingxia , Gao Menghan , Liu Weixia , Li Yuting , Tian Suyan , Sun Chenglin 

TITLE=To explore association between gamma-glutamyl transferase and type 2 diabetes using a real-world study and mendelian randomization analysis

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.899008

DOI=10.3389/fendo.2022.899008

ISSN=1664-2392

ABSTRACT=<sec><title>Aim</title><p>The association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) is controversial. In this study, we investigated the association between GGT and the risk of T2DM using real-world data, Mendelian randomization (MR) analysis, and literature mining.</p></sec><sec><title>Methods</title><p>A cross-sectional study enrolled 3,048 participants (&gt;40 years) from a community in Northeastern China was conducted. A generalized additive model was used to examine the relation between GGT and T2DM. A two-sample MR was performed to investigate the causal effect of GGT (61,089 individuals, mostly of European ancestry) on T2DM (29,193 cases and 182,573 controls of European ancestry).</p></sec><sec><title>Results</title><p>GGT was related to glucose metabolism indicators, such as fasting plasma glucose and glycosylated hemoglobin (<italic>P</italic> &lt; 0.05). The odds ratios (ORs) [95% confidence interval (95% CI), <italic>P</italic>] for T2DM across the GGT categories (14–16, 17–20, 21–25, 26–35, ≥36) were 1.14 [(0.88-1.47), <italic>P</italic> = 0.330], 1.55 [(1.22-1.98), <italic>P</italic> &lt; 0.001], 1.87 [(1.47-2.28), <italic>P</italic> &lt; 0.001], 1.97 [(1.55-2.52), <italic>P</italic> &lt; 0.001], and 2.29 [(1.78-2.94), <italic>P</italic> &lt; 0.001] versus GGT ≤ 13 category after adjusting for potential confounding factors. A generalized additive model identified a non-linear correlation between GGT and T2DM and indicated that the risk of T2DM almost levelled out when GGT exceeded 34 IU/L. The MR analysis showed that the odds of having T2DM for a one-time increase in genetically determined GGT was 0.998 [(0.995-1.002), <italic>P</italic> = 0.34].</p></sec><sec><title>Conclusions</title><p>Our analysis of observational study suggested that GGT, its increment, within a certain range, is indicative of the development of T2DM. However, MR analysis provided no evidence that GGT is a linear causal factor of T2DM. Further investigation is required to determine if GGT exerts a non-linear causal effect on T2DM.</p></sec>