Evidence map›Paper›PMID 41837567›Full record

ArticleDiabetes care2026

A U-Shaped Association Between Blood mtDNA Copy Number and Risk of Type 2 Diabetes.

Xinhao Huang, Zijian Tian, Ying Pan, Jia Zhang, Benrui Wu, Shiteng Gao, Yao Cheng, Qi Hu, Jinxiang Ma, Qi Pan and 2 more

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Article in Diabetes care, 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

Authors and funding

12 authors.

Xinhao HuangSchool of Public Health, Guangzhou Medical University, Guangzhou, China.ORCID 0009-0001-6340-3435
Zijian TianNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.ORCID 0000-0002-2182-5381
Ying PanDepartment of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, China.ORCID 0000-0001-9935-6194
Jia ZhangDepartment of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.ORCID 0000-0003-4456-2243
Benrui WuNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.ORCID 0009-0005-3013-4995
Shiteng GaoSchool of Public Health, Guangzhou Medical University, Guangzhou, China.ORCID 0009-0005-6578-5982
Yao ChengGuangzhou National Laboratory, Guangzhou, China.ORCID 0009-0006-1036-8177
Qi HuSchool of Public Health, Guangzhou Medical University, Guangzhou, China.ORCID 0009-0006-6225-2053
Jinxiang MaSchool of Public Health, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-4088-4141
Qi PanDepartment of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.ORCID 0000-0002-2567-1439
Jian ShaoSchool of Public Health, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0001-7828-3459
Kaixin ZhouSchool of Public Health, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-4751-7248

Funding

National High Level Hospital Clinical Research Funding BJ-2024-144National Key R&D Program of China 2022YFB3203704Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0531900Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0531903
6 · The paper itself

Abstract

objectivemtDNA copy number (CN) reflects mitochondrial function, but prior studies have reported inconsistent associations with type 2 diabetes risk, ranging from inverse to positive or null findings. We hypothesized that mtDNA-CN is nonlinearly associated with incident type 2 diabetes. RESEARCH DESIGN AND

methodsWe included 34,835 adults without diabetes from the Kunshan Aging Research With E-Health (KARE) cohort and 289,338 from the UK Biobank (UKB). Associations between blood mtDNA-CN and incident type 2 diabetes were evaluated using Cox proportional hazards and restricted cubic spline models stratified by age.

resultsA U-shaped association was observed in the KARE cohort (P < 0.001), in which the hazard ratios (95% CIs) across increasing mtDNA-CN quartiles were 1.00 (reference), 0.94 (0.88-1.00), 0.85 (0.79-0.91), and 0.93 (0.87-1.00). In contrast, the UKB cohort exhibited a predominantly inverse linear trend. Age-stratified analyses revealed that this U-shaped association was particularly evident in younger participants (aged <65 years in KARE and <50 years in UKB), indicating elevated diabetes risk at both low and high mtDNA-CN levels. Additionally, mtDNA-CN declined with age in both cohorts, with an accelerated decrease beyond ∼65 years in KARE and ∼50 years in UKB.

conclusionsBlood mtDNA-CN showed a U-shaped association with incident type 2 diabetes in younger individuals.

Indexed as

Diabetes Mellitus, Type 2DNA Copy Number VariationsDNA, MitochondrialAgedCohort StudiesFemaleHumansMaleMiddle AgedDNA, Mitochondrial

Identifiers

PMID41837567
PMCPMC13094880

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