AUTHOR=Yu Yunfeng , Hu Gang , Yang Xinyu , Bai Siyang , Wu Jingyi , Tong Keke , Yu Rong TITLE=Effect of post-traumatic stress disorder on type 2 diabetes and the mediated effect of obesity: a Mendelian randomization study JOURNAL=Frontiers in Endocrinology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1375068 DOI=10.3389/fendo.2024.1375068 ISSN=1664-2392 ABSTRACT=Objective

Whether the role of post-traumatic stress disorder (PTSD) on type 2 diabetes (T2D) is mediated by obesity or other mediating factors is controversial. This study was designed to assess the impact of PTSD on genetic susceptibility to T2D and mediating factors.

Methods

The datasets for PTSD, T2D, obesity, hypertension, hyperlipidemia, smoking status, and alcohol consumption were obtained from genome-wide association studies. Mendelian randomization (MR) was used to assess exposure-outcome causality, and inverse variance weighted was used as the primary tool for MR analysis. MR-Egger intercept, Cochran’s Q, and leave-one-out sensitivity analysis were employed to assess horizontal pleiotropy, heterogeneity, and robustness, respectively.

Results

The MR analysis showed that PTSD was associated with increased genetic susceptibility to T2D (OR, 1.036; 95% CI, 1.008-1.064; p = 0.011), obesity (OR, 1.033; 95% CI, 1.016-1.050; p < 0.001), and hypertension (OR, 1.002; 95% CI, 1.000-1.003; p = 0.015), but not not with genetic susceptibility to hyperlipidemia, alcohol consumption, and smoking status (p ≥ 0.05). Mediated effect analysis showed that PTSD increased genetic susceptibility to T2D by increasing genetic susceptibility to obesity and hypertension, with obesity accounting for 9.51% and hypertension accounting for 2.09%. MR-Egger intercept showed no horizontal pleiotropy (p ≥ 0.05). Cochran’s Q showed no heterogeneity (p ≥ 0.05). Leave-one-out sensitivity analysis showed that the results were robust.

Conclusion

This MR analysis suggests that PTSD increases the risk of T2D and that this effect is partially mediated by obesity and hypertension. Active prevention and treatment of PTSD can help reduce the risk of T2D.