The impacts of long-term carbon disulfide exposure on glucose homeostasis and type 2 diabetes: a multifaceted gene-environment-lifestyle interaction study of Chinese adults
Yueru Yang, Jiahao Song, Yongfang Zhang, Shuhui Wan, Zhi-Ying Huo, Qing Liu, Le Huynh Thi Cam Hong, Linling Yu, Wei Liu, Ruyi Liang, Bin Wang, Weihong Chen
Abstract
• Long-term CS 2 exposure impaired glucose homeostasis and increased T2D risk. • Gene-CS 2 -lifestyle interactions on glucose dyshomeostasis and T2D were identified. • High genetic risk aggravated CS 2 -related glucose dyshomeostasis and T2D risk. • Healthy lifestyle alleviated CS 2 -related glucose dyshomeostasis and T2D risk. • Reduce CS 2 and improve lifestyle help to prevent T2D especially for those at high genetic risk. The long-term impacts of exposure to carbon disulfide (CS 2 ), a highly concerning air toxicant listed by the Clean Air Act, and its interactions with genetic susceptibility and lifestyle on glucose homeostasis and type 2 diabetes (T2D) in the general population remain unclear and require urgent clarification. To investigate the interactions of CS 2 exposure, genetic susceptibility, and lifestyle on glucose homeostasis and T2D. In this prospective study, urinary CS 2 metabolite (2-Thiothiazolidine-4-carboxylic acid, TTCA) and fasting plasma glucose (FPG) and insulin (FPI) for 5294 observations from 2523 participants were repeatedly measured to examine the cross-sectional and longitudinal associations of CS 2 exposure with glucose homeostasis and T2D by performing generalized linear mixed models or COX models. Polygenic risk score (PRS) and healthy lifestyle index (HLI) were constructed to evaluate their cross-sectional and longitudinal interactions with TTCA and to assess gene-CS 2 -lifestyle interactions. TTCA was cross-sectionally and longitudinally related to glucose dyshomeostasis and T2D risk elevation. Longitudinally, compared to subjects with persistently low TTCA, those with persistently high TTCA had 0.350 (95 % CI: 0.060 ∼ 0.640) mmol/L, 0.197 (0.097 ∼ 0.297) ln-unit, 0.236 (0.120 ∼ 0.351) ln-unit, and 56.3 % (HR: 1.563; 95 % CI: 1.018 ∼ 2.401) risk increments in FPG, FPI, HOMA-IR, and T2D incidence, respectively. Cross-sectional and longitudinal interactions of TTCA with PRS and HLI were uncovered ( P for interaction < 0.05). Subjects with persistently low TTCA, healthy lifestyle, and low PRS longitudinally manifested the greatest reductions in FPG (β: −0.609; 95 % CI: −1.108 ∼ -−0.108), FPI (−0.357; −0.479 ∼ -−0.236), HOMA-IR (−0.358; −0.498 ∼ -−0.219), and incident T2D risk (HR: 0.228; 95 % CI: 0.091 ∼ 0.574). Long-term CS 2 exposure was related to glucose dyshomeostasis and increased T2D risk, which might be exacerbated by high genetic susceptibility while mitigated by healthy lifestyle, highlighting the significance of reducing CS 2 exposure and improving lifestyle in preventing glucose dyshomeostasis and T2D, particularly among individuals with high genetic risk.