BackgroundRisk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China.MethodsWe included data from 5706 people with normal body mass index (BMI) (18.5–23.9 kg/m2) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure–response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2].ResultsRisk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20–5.11], 3.77 [1.83–7.79], and 5.30 [2.21–12.71], P trend < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22–6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index.ConclusionsRisk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.

Ure2p is the precursor protein of the Saccharomyces cerevisiae prion [URE3]. Ure2p shows homology to glutathione transferases but lacks typical glutathione transferase activity. A recent study found that deletion of the Ure2 gene causes increased sensitivity to heavy metal ions and oxidants, whereas prion strains show normal sensitivity. To demonstrate that protection against oxidant toxicity is an inherent property of native and prion Ure2p requires biochemical characterization of the purified protein. Here we use steady-state kinetic methods to characterize the multisubstrate peroxidase activity of Ure2p using GSH with cumene hydroperoxide, hydrogen peroxide, or tert-butyl hydroperoxide as substrates. Glutathione-dependent peroxidase activity was proportional to the Ure2p concentration and showed optima at pH 8 and 40°C. Michaelis-Menten behavior with convergent straight lines in double reciprocal plots was observed. This excludes a ping-pong mechanism and implies either a rapid-equilibrium random or a steady-state ordered sequential mechanism for Ure2p, consistent with its classification as a glutathione transferase. The mutant 90Ure2, which lacks the unstructured N-terminal prion domain, showed kinetic parameters identical to wild type. Fibrillar aggregates showed the same level of activity as native protein. Demonstration of peroxidase activity for Ure2 represents important progress in elucidation of its role in vivo. Further, establishment of an in vitro activity assay provides a valuable tool for the study of structure-function relationships of the Ure2 protein as both a prion and an enzyme.