Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database

Abstract Background The α-klotho is crucial in diabetes and its related complications. This study seeks to explore the link between α-klotho levels and the risk of diabetic kidney disease (DKD) as well as all-cause and cardiovascular mortality among individuals with type 2 diabetes mellitus (T2DM)....

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Main Authors: Yi Kang, Qian Jin, Mengqi Zhou, Huijuan Zheng, Danwen Li, Jingwei Zhou, Jie Lv, Yaoxian Wang
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Diabetology & Metabolic Syndrome
Subjects:
Online Access:https://doi.org/10.1186/s13098-025-01711-x
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author Yi Kang
Qian Jin
Mengqi Zhou
Huijuan Zheng
Danwen Li
Jingwei Zhou
Jie Lv
Yaoxian Wang
author_facet Yi Kang
Qian Jin
Mengqi Zhou
Huijuan Zheng
Danwen Li
Jingwei Zhou
Jie Lv
Yaoxian Wang
author_sort Yi Kang
collection DOAJ
description Abstract Background The α-klotho is crucial in diabetes and its related complications. This study seeks to explore the link between α-klotho levels and the risk of diabetic kidney disease (DKD) as well as all-cause and cardiovascular mortality among individuals with type 2 diabetes mellitus (T2DM). Methods The investigation involved 126 Chinese T2DM patients and 4,451 individuals from the National Health and Nutrition Examination Survey (NHANES) database. To evaluate the relationship between α-klotho levels and DKD risk, multivariate logistic regression was utilized. Additionally, restricted cubic spline (RCS) regression analysis was conducted to examine the nonlinear relationship between α-klotho levels and DKD incidence. RCS analysis was employed to explore the correlation between α-klotho and both all-cause and cardiovascular mortality. Results In the Chinese cohort, α-klotho levels were notably elevated in T2DM group compared to DKD group. The NHANES data revealed a significant inverse relationship between α-klotho levels and DKD risk. Nonlinear analysis further illustrated a substantial nonlinear connection between α-klotho levels and DKD risk. Serum α-klotho levels below 880.78 pg/mL were linked to increased DKD risk in T2DM patients. When compared to the T2DM group, the DKD group had markedly higher all-cause and cardiovascular mortality rates, with the α-klotho low group (e.g., Q1) exhibiting lower survival compared to other groups. Cox regression findings indicated that elevated α-klotho levels could mitigate all-cause mortality in T2DM patients. The relationship between α-klotho levels and all-cause mortality was also nonlinear, with the minimal risk found at α-klotho levels between 776.95 pg/mL and 812.69 pg/mL, varying by gender. Conclusion There exists a notable association between α-klotho levels and DKD risk, along with mortality in T2DM patients, with varying effects based on gender. These results highlight the potential importance of α-klotho as both a biomarker and a therapeutic target.
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series Diabetology & Metabolic Syndrome
spelling doaj-art-86c097e80edb4be09f5efdb48bb4b4f42025-08-20T02:10:54ZengBMCDiabetology & Metabolic Syndrome1758-59962025-05-0117111410.1186/s13098-025-01711-xAssociation between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES databaseYi Kang0Qian Jin1Mengqi Zhou2Huijuan Zheng3Danwen Li4Jingwei Zhou5Jie Lv6Yaoxian Wang7Dongzhimen Hospital, Beijing University of Chinese MedicineGraduate School of Beijing, University of Chinese MedicineDepartment of Traditional Chinese Medicine, Beijing Puren HospitalDongzhimen Hospital, Beijing University of Chinese MedicineDongzhimen Hospital, Beijing University of Chinese MedicineDongzhimen Hospital, Beijing University of Chinese MedicineDongzhimen Hospital, Beijing University of Chinese MedicineDongzhimen Hospital, Beijing University of Chinese MedicineAbstract Background The α-klotho is crucial in diabetes and its related complications. This study seeks to explore the link between α-klotho levels and the risk of diabetic kidney disease (DKD) as well as all-cause and cardiovascular mortality among individuals with type 2 diabetes mellitus (T2DM). Methods The investigation involved 126 Chinese T2DM patients and 4,451 individuals from the National Health and Nutrition Examination Survey (NHANES) database. To evaluate the relationship between α-klotho levels and DKD risk, multivariate logistic regression was utilized. Additionally, restricted cubic spline (RCS) regression analysis was conducted to examine the nonlinear relationship between α-klotho levels and DKD incidence. RCS analysis was employed to explore the correlation between α-klotho and both all-cause and cardiovascular mortality. Results In the Chinese cohort, α-klotho levels were notably elevated in T2DM group compared to DKD group. The NHANES data revealed a significant inverse relationship between α-klotho levels and DKD risk. Nonlinear analysis further illustrated a substantial nonlinear connection between α-klotho levels and DKD risk. Serum α-klotho levels below 880.78 pg/mL were linked to increased DKD risk in T2DM patients. When compared to the T2DM group, the DKD group had markedly higher all-cause and cardiovascular mortality rates, with the α-klotho low group (e.g., Q1) exhibiting lower survival compared to other groups. Cox regression findings indicated that elevated α-klotho levels could mitigate all-cause mortality in T2DM patients. The relationship between α-klotho levels and all-cause mortality was also nonlinear, with the minimal risk found at α-klotho levels between 776.95 pg/mL and 812.69 pg/mL, varying by gender. Conclusion There exists a notable association between α-klotho levels and DKD risk, along with mortality in T2DM patients, with varying effects based on gender. These results highlight the potential importance of α-klotho as both a biomarker and a therapeutic target.https://doi.org/10.1186/s13098-025-01711-xα-klothoType 2 diabetesDiabetic kidney diseaseAll-cause mortalityCardiovascular mortality
spellingShingle Yi Kang
Qian Jin
Mengqi Zhou
Huijuan Zheng
Danwen Li
Jingwei Zhou
Jie Lv
Yaoxian Wang
Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database
Diabetology & Metabolic Syndrome
α-klotho
Type 2 diabetes
Diabetic kidney disease
All-cause mortality
Cardiovascular mortality
title Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database
title_full Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database
title_fullStr Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database
title_full_unstemmed Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database
title_short Association between serum α-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database
title_sort association between serum α klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes evidence from a chinese cohort and the nhanes database
topic α-klotho
Type 2 diabetes
Diabetic kidney disease
All-cause mortality
Cardiovascular mortality
url https://doi.org/10.1186/s13098-025-01711-x
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