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

ObjectiveTo 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).MethodsAccording to the urinary al...

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Main Authors: Pingping Zhao, Xiaoyu Lv, Zhicong Zhou, Xiaolan Yang, Ying Huang, Jingfang Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-12-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1297166/full
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author Pingping Zhao
Xiaoyu Lv
Zhicong Zhou
Xiaolan Yang
Ying Huang
Jingfang Liu
Jingfang Liu
author_facet Pingping Zhao
Xiaoyu Lv
Zhicong Zhou
Xiaolan Yang
Ying Huang
Jingfang Liu
Jingfang Liu
author_sort Pingping Zhao
collection DOAJ
description ObjectiveTo 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).MethodsAccording 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.ResultsTo 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.ConclusionDN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.
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spelling doaj.art-f2e03e1db81649a5b4b1db45a51f5e292023-12-22T11:10:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12971661297166Indexes of ferroptosis and iron metabolism were associated with the severity of diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional studyPingping Zhao0Xiaoyu Lv1Zhicong Zhou2Xiaolan Yang3Ying Huang4Jingfang Liu5Jingfang Liu6The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, ChinaThe First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, ChinaKangle Dental Clinic, Baiyin, Gansu, ChinaClinical Laboratory of The First People’s Hospital of Baiyin, Baiyin, Gansu, ChinaClinical Laboratory of The First People’s Hospital of Baiyin, Baiyin, Gansu, ChinaThe First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaObjectiveTo 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).MethodsAccording 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.ResultsTo 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.ConclusionDN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.https://www.frontiersin.org/articles/10.3389/fendo.2023.1297166/fulltype 2 diabetesferroptosisGPx4ACSL4iron metabolism
spellingShingle Pingping Zhao
Xiaoyu Lv
Zhicong Zhou
Xiaolan Yang
Ying Huang
Jingfang Liu
Jingfang Liu
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
Frontiers in Endocrinology
type 2 diabetes
ferroptosis
GPx4
ACSL4
iron metabolism
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic type 2 diabetes
ferroptosis
GPx4
ACSL4
iron metabolism
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1297166/full
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