Triglyceride-glucose index is prospectively associated with chronic kidney disease progression in Type 2 diabetes – mediation by pigment epithelium-derived factor
Serena Low, Sharon Li Ting Pek, Angela Moh, Keven Ang, Jonathon Khoo, Yi Ming Shao, Wern Ee Tang, Ziliang Lim, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim
Abstract
Background Triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance. Its role in chronic kidney disease (CKD) progression in Type 2 Diabetes Mellitus (T2DM) is unclear. We investigated the association between TyG index and CKD progression, and possible mediation of the association by pigment epithelium-derived factor (PEDF). Methods This was a prospective study on 1571 patients with T2DM. CKD progression was defined as worsening across KDIGO estimated glomerular filtration rate (eGFR) categories with ≥25% reduction from baseline. PEDF was quantitated using enzyme-linked immunosorbent assay method. Cox proportional hazards regression model was used to assess the relationship between TyG index and CKD progression. Results Over a follow-up period of up to 8.6 years (median 4.6 years, IQR 3.0–3.6), 42.7% of subjects had CKD progression. Every unit increase in TyG was associated with hazards of 1.44 (95%CI 1.29–1.61; p < 0.001) in unadjusted analysis and 1.21 (1.06–1.37; p = 0.004) in fully adjusted model. Compared to tertile 1, tertiles 2 and 3 TyG index were positively associated with CKD progression with corresponding hazard ratios HRs 1.24 (1.01–1.52; p = 0.037) and 1.37 (1.11–1.68; p = 0.003) in fully adjusted models. PEDF accounted for 36.0% of relationship between TyG index and CKD progression. Conclusions Higher TyG index independently predicted CKD progression in T2DM. PEDF mediated the association between TyG index and CKD progression.