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

Pingping Zhao; Xiaoyu Lv; Zhicong Zhou; Xiaolan Yang; Ying Huang; Jingfang Liu

doi:10.3389/fendo.2023.1297166

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

Front Endocrinol (Lausanne). 2023 Dec 22:14:1297166. doi: 10.3389/fendo.2023.1297166. eCollection 2023.

Authors

Pingping Zhao¹, Xiaoyu Lv¹, Zhicong Zhou², Xiaolan Yang³, Ying Huang³, Jingfang Liu^{1

4}

Affiliations

¹ The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
² Kangle Dental Clinic, Baiyin, Gansu, China.
³ Clinical Laboratory of The First People's Hospital of Baiyin, Baiyin, Gansu, China.
⁴ Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.

Abstract

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 [β = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [β = -1.633, 95% CI (-2.77, -0.496)] and Tf [β = -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.

Keywords: ACSL4; GPx4; ferroptosis; iron metabolism; type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Albuminuria
Cross-Sectional Studies
Diabetes Mellitus, Type 2* / complications
Diabetic Nephropathies* / etiology
Ferritins
Ferroptosis*
Humans
Iron
Transferrin

Substances

Iron
Transferrin
Ferritins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by National Natural Science Foundation of China (No.81960155 and No.82360161), Natural Science Foundation of Gansu Province (20JR10RA690).