U-Shaped Association Between the Triglycerides-Glucose index and the Risk of Incident Diabetes in Apparently Healthy Population: A Population-based Cohort Study

Abstract Background Although the triglycerides-glucose (TyG) index was thought to be a practical predictor of incident diabetes, the association between them has not been well characterized. The study aimed to further examine the association between the TyG index and incident diabetes in Japanese adults. Methods The cases were extracted of the individual participating in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study at Murakami Memorial Hospital from 2004 to 2015, and 14297individuals apparently healthy at baseline were included in the study. Cox proportional hazards models were used to evaluate the associations between baseline TyG levels and incident of T2DM, and a two-piecewise linear regression model was use to examine the threshold effect of the baseline TyG on incident diabetes using a smoothing function. The threshold level (i.e., turning point) was determined using trial and error. A log likelihood ratio test was also conducted to compare the one-line linear regression model with a two-piecewise linear model. Results During a median follow-up period of 5.26 (women) and 5.88 (men) years, 47 women and 182 men developed Type 2 diabetes. The risk of diabetes was strongly associated with the baseline TyG index in the fully adjusted model in men but not in women, and no dose-dependent positive relationship between incident diabetes and TyG was observed across TyG tertiles. Intriguingly, two-piecewise linear regression analysis showed a U-shaped association between the TyG index and incident T2DM. The risk of incident diabetes decreased by around 90% in women with TyG < 7.27 (HR: 0.09; P = 0.0435) and 80% in men with TyG < 7.97 (HR 0.21, P = 0.002) with each increment of the TyG index after adjusting for confounders. In contrast, the risk of incident T2DM significantly elevated with the increase in TyG index in men with TyG > 7.97 (HR: 2.42, P < 0.001) and women with TyG > 7.29 (HR 2.76, P = 0.0166). Conclusions A U-shaped association was observed between the TyG index and incident T2DM among healthy individuals, with the TyG threshold of 7.97 in men and 7.27 in women. This information may be useful for reducing incident diabetes by maintaining the TyG index near these thresholds.