Evidence map›Paper›PMID 41692750›Full record

ArticleCardiovascular diabetology2026

Proteomics-derived organ-specific aging clusters predict macrovascular and microvascular complications in diabetes.

Sheng Yuan, Zhangyu Lin, Yanjun Song, Ketai Shi, Jingjing Guan, Zhiyong Zhao, Kefei Dou

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Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Sheng Yuan *State Key Laboratory of Cardiovascular Disease, Beijing, China.
Zhangyu Lin *State Key Laboratory of Cardiovascular Disease, Beijing, China.
Yanjun Song *State Key Laboratory of Cardiovascular Disease, Beijing, China.
Ketai ShiDepartment of MedicineMetropolitan Hospital Center, New York Medical College, New York, NY, USA.
Jingjing GuanDepartment of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Zhiyong ZhaoCardiometabolic Medicine Center, National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, A 167 Beilishi Rd, Xicheng District, Beijing, 100037, China. pumc_zhaozy@126.com.
Kefei DouState Key Laboratory of Cardiovascular Disease, Beijing, China. drdoukefei@126.com.

Funding

Noncommunicable Chronic Diseases-National Science and Technology Major Project 2025ZD0548200Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation GZC20251535
6 · The paper itself

Abstract

backgroundAging is intrinsically linked to diabetes pathogenesis, yet evidence gaps persist regarding organ-specific aging and risks of long-term diabetes complications. This study aims to estimate the association between plasma proteomics-based organ-specific aging and risks of long-term diabetes complications.

methodsThis cohort study quantified biological age gaps (residuals from linear regression of predicted versus chronological age) across 11 organ systems in 1979 baseline diabetes patients based on plasma proteomic profiling (Olink Explore 3072) of 2916 proteins and three validated different aging models. Extreme aging was defined as > 1.5 standard deviation from organ-specific mean age gaps. Multivariable Cox models assessed incident complication risks in 1707 complication-free patients.

resultsDuring a median follow-up time of 12.71 years, 356 incident all-cause deaths (20.86%), 348 incident cardiovascular disease (CVD) (20.39%), 227 incident diabetic retinopathy (DR) (13.30%), 88 incident peripheral artery disease (PAD) (5.16%), and 280 incident chronic kidney disease (CKD) (16.40%) occurred. Extreme cardiac aging showed strongest CVD risk association (adjusted HR: 2.92, 95% CI: 2.13, 3.99; P < 0.001), with significant brain (adjusted HR: 1.43, 95% CI: 1.06, 1.92; P = 0.019), arterial (adjusted HR: 1.59, 95% CI: 1.06, 2.39; P = 0.024), and pancreatic (adjusted HR: 1.35, 95% CI: 1.04, 1.77; P = 0.027) aging associations. Each complication demonstrated distinct organ-aging signatures. The association remains robust and consistent across three distinct aging models. Patients with baseline extreme aging in more than 3 organs faced significantly higher risks of incident diabetes complications compared to those with no or only one to three extremely aged organs. Additive interaction analysis revealed synergistic effects of organ aging on complications risk in diabetes. For example, concurrent heart and muscle aging substantially elevated CVD risk with a relative excess risk due to interaction (RERI) of 3.49 (95% CI: 0.74, 8.16) and an attributable proportion (AP) of 0.58 (95% CI: 0.14, 0.74).

conclusionsProteomics-based organ aging assessment identifies significant complication-specific vulnerability patterns and substantially elevated risks with multiorgan involvement, supporting comprehensive aging evaluation for diabetes risk stratification. These findings require further validation in larger and more diverse populations and warrant more precise characterization of organ-specificity to enhance their robustness and generalizability.

Indexed as

AgingBlood ProteinsDiabetic AngiopathiesProteomicsAgedAge FactorsBiomarkersFemaleHumansIncidenceMaleMiddle AgedPrognosisRisk AssessmentRisk FactorsTime FactorsBiomarkersBlood ProteinsAgingComplicationsDiabetesProteomics

Identifiers

PMID41692750
PMCPMC13011696

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