Triglyceride-glucose index is prospectively associated with chronic kidney disease progression in Type 2 diabetes - mediation by pigment epithelium-derived factor

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.