Ferroptosis-Associated Iron and Lipid Biomarkers in Early Diabetic Kidney Disease in Adults with Type 2 Diabetes Mellitus

Abstract

Diabetic kidney disease (DKD) is detected late by conventional markers such as serum creatinine and microalbuminuria. Ferroptosis has been proposed as an early contributor to diabetic renal injury; this study examined iron-status and lipid parameters as indirect, hypothesis-generating correlates. We evaluated serum ferritin, transferrin, TIBC, transferrin saturation (TSAT), and fasting lipids in 180 adults at UITH, Ilorin, Nigeria: 60 with type 2 diabetes (T2DM) and early DKD, 60 with T2DM and preserved renal function, and 60 healthy controls. Ferritin and transferrin were higher, and TSAT lower, in both T2DM groups than controls (all p<0.0001); TIBC and TSAT were additionally lower in early DKD than in T2DM without DKD (TIBC: 12.2 vs 17.7 µmol/L, p<0.0001; TSAT: 18.0% vs 25.0%, p<0.0001), with every early-DKD TSAT value below every no-DKD value. LDL-C rose progressively across all three groups (all pairwise p<0.002); triglycerides and glucose were higher, and HDL-C lower, in both diabetic groups than controls (all p<0.0001). Among T2DM patients, ferritin and TIBC correlated with lipid/glycaemic indices (most FDR-adjusted q<0.01); TSAT did not, beyond a borderline, FDR-non-significant link with triglycerides. In univariable, log-transformed, standardised logistic regression, lower TSAT and TIBC were associated with early DKD; TSAT showed complete separation between the two T2DM groups, requiring Firth's method (OR 0.006, 95% CI 0.001–0.054, p<0.0001), while TIBC showed a conventional association (OR 0.27, 95% CI 0.14–0.55, p=0.0003); ferritin's association attenuated after log-transformation (p=0.18). No confounder adjustment was performed. TSAT's near-complete separation is a striking signal warranting prospective, multi-centre replication before diagnostic use