Indexes of ferroptosis and iron metabolism were associated with the severity of diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study

Objective: To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM).Methods: According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR >= 90 mL/min), G2 (eGFR <= 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively.Results: To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [beta = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [beta = -1.633, 95% CI (-2.77, -0.496)] and Tf [beta = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, p =0.015 and 0.001], and Tf (OR = 0.109 and 0.119, p =0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both p <0.001) in the MA group.Conclusion: DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.