U-shaped association between the triglyceride-glucose index and the risk of incident diabetes in people with normal glycemic level: A population-base longitudinal cohort study

Background: Previous studies have shown that a high baseline triglyceride-glucose (TyG) index is a potential risk factor for type 2 diabetes mellitus (T2DM). However, for a low TyG index, findings have been inconsistent. Moreover, the association between the baseline TyG index and incident T2DM in individuals with normal glycemic levels remains unclear. Therefore, this longitudinal study further examined and characterized the association between the baseline TyG index and incident T2DM in Japanese adults with normal glycemic levels.. Methods: The participants (7857 men and 6440 women) were selected from the NAGALA (NAfld in the Gifu Area Longitudinal Analysis) study that was conducted from 2004 to 2015. Cox proportional hazards models were used to evaluate the associations between baseline TyG index and T2DM incidence, and a two-piecewise linear regression model was used to examine the threshold effect of the baseline TyG index on incident T2DM using a smoothing function. Results: During a median follow-up period of 5.26 (women) and 5.88 (men) years, 47 women and 182 men developed T2DM. The risk of T2DM 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 T2DM and the TyG index was observed across the TyG tertiles. Interestingly, the two-piecewise linear regression analysis revealed a U-shaped association between the baseline TyG index and incident T2DM. Baseline TyG index lower than the threshold values (TyG index < 7.27 in women and <7.97 in men) were negatively associated with incident T2DM (hazard ratio [HR] = 0.09, 95% confidence interval [CI] = 0.01-0.93, P = 0.0435 for women and HR = 0.21, 95% CI = 0.08-0.57, P = 0.0021 for men). In contrast, baseline TyG index higher than the threshold values (TyG index > 7.27 in women and >7.97 in men) were positively associated with incident T2DM (HR = 2.76, 95% CI = 1.20-6.34, P = 0.0166 for women and HR = 2.42, 95% CI = 1.66-3.53, P < 0.0001 for men). Conclusions: A U-shaped association was observed between the baseline TyG index and incident T2DM in a Japanese population. (c) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.