Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis

Background Elevated body mass index (BMI) has been implicated in the pathogenesis of diabetic kidney disease among patients with type 2 diabetes mellitus (T2DKD). However, establishing a causal relationship and quantifying the resultant global health impact remain challenging.Methods A two-sample Me...

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Main Authors: Ye-xin Chen, Dong-sen Hu, Mao-xuan Lin, Zi-heng Gao, Han-zhang Hong, Yu-xin Hu, Ling-zi Yao, Gai-wen Cui, Lin Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2472981
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author Ye-xin Chen
Dong-sen Hu
Mao-xuan Lin
Zi-heng Gao
Han-zhang Hong
Yu-xin Hu
Ling-zi Yao
Gai-wen Cui
Lin Wang
author_facet Ye-xin Chen
Dong-sen Hu
Mao-xuan Lin
Zi-heng Gao
Han-zhang Hong
Yu-xin Hu
Ling-zi Yao
Gai-wen Cui
Lin Wang
author_sort Ye-xin Chen
collection DOAJ
description Background Elevated body mass index (BMI) has been implicated in the pathogenesis of diabetic kidney disease among patients with type 2 diabetes mellitus (T2DKD). However, establishing a causal relationship and quantifying the resultant global health impact remain challenging.Methods A two-sample Mendelian randomization (MR) analysis was conducted using summary-level data obtained from the IEU database. Multiple MR approaches, including inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and simple mode methods, were implemented to ensure robust causal inference. In parallel, Global Burden of Disease Study (GBD) 2021 were analyzed to determine the trends in mortality and disability-adjusted life years (DALYs) in T2DKD attributable to high BMI (HBMI-T2DKD) from 1990 to 2021. Joinpoint regression was used to estimate the average annual percent change (AAPC). Bayesian age-period-cohort (BAPC) models were then applied to project the disease burden through 2049.Results MR analyses provided strong evidence for a causal relationship between elevated BMI and T2DKD. The GBD analysis revealed a sustained global increase in HBMI-T2DKD burden over the past three decades. Between 1990 and 2021, the result of AAPC indicated a persistent upward trend. The burden was particularly high among older adults, with the highest impact observed in East Asia and middle Socio-Demographic Index (SDI) region. By 2049, HBMI-T2DKD-related disease burden were projected to continue rising.Conclusions Elevated BMI is a significant causal risk factor for T2DKD. The integration of MR and GBD 2021 data underscores the urgent need for targeted public health interventions to reduce BMI levels, especially in high-risk regions and aging populations.
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spelling doaj-art-425aa1fbcf974a7391f05ee15a187c2f2025-08-20T03:42:37ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2472981Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysisYe-xin Chen0Dong-sen Hu1Mao-xuan Lin2Zi-heng Gao3Han-zhang Hong4Yu-xin Hu5Ling-zi Yao6Gai-wen Cui7Lin Wang8Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaBeijing University of Chinese Medicine, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Public Health, Zhejiang University School of Medicine, Hangzhou, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaDongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaBackground Elevated body mass index (BMI) has been implicated in the pathogenesis of diabetic kidney disease among patients with type 2 diabetes mellitus (T2DKD). However, establishing a causal relationship and quantifying the resultant global health impact remain challenging.Methods A two-sample Mendelian randomization (MR) analysis was conducted using summary-level data obtained from the IEU database. Multiple MR approaches, including inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and simple mode methods, were implemented to ensure robust causal inference. In parallel, Global Burden of Disease Study (GBD) 2021 were analyzed to determine the trends in mortality and disability-adjusted life years (DALYs) in T2DKD attributable to high BMI (HBMI-T2DKD) from 1990 to 2021. Joinpoint regression was used to estimate the average annual percent change (AAPC). Bayesian age-period-cohort (BAPC) models were then applied to project the disease burden through 2049.Results MR analyses provided strong evidence for a causal relationship between elevated BMI and T2DKD. The GBD analysis revealed a sustained global increase in HBMI-T2DKD burden over the past three decades. Between 1990 and 2021, the result of AAPC indicated a persistent upward trend. The burden was particularly high among older adults, with the highest impact observed in East Asia and middle Socio-Demographic Index (SDI) region. By 2049, HBMI-T2DKD-related disease burden were projected to continue rising.Conclusions Elevated BMI is a significant causal risk factor for T2DKD. The integration of MR and GBD 2021 data underscores the urgent need for targeted public health interventions to reduce BMI levels, especially in high-risk regions and aging populations.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2472981Mendelian RandomizationGlobal Burden of Disease Study 2021diabetic kidney diseaseelevated body mass indextype 2 diabetes mellituschronic kidney disease
spellingShingle Ye-xin Chen
Dong-sen Hu
Mao-xuan Lin
Zi-heng Gao
Han-zhang Hong
Yu-xin Hu
Ling-zi Yao
Gai-wen Cui
Lin Wang
Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis
Renal Failure
Mendelian Randomization
Global Burden of Disease Study 2021
diabetic kidney disease
elevated body mass index
type 2 diabetes mellitus
chronic kidney disease
title Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis
title_full Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis
title_fullStr Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis
title_full_unstemmed Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis
title_short Causal impact of elevated body mass index on diabetic kidney disease: an integrated Mendelian randomization and Global Burden of Disease Study 2021 analysis
title_sort causal impact of elevated body mass index on diabetic kidney disease an integrated mendelian randomization and global burden of disease study 2021 analysis
topic Mendelian Randomization
Global Burden of Disease Study 2021
diabetic kidney disease
elevated body mass index
type 2 diabetes mellitus
chronic kidney disease
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2472981
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