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

IF 16.6 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Care Pub Date : 2026-03-16 DOI:10.2337/dc25-2198

Xinhao Huang, Zijian Tian, Ying Pan, Jia Zhang, Benrui Wu, Shiteng Gao, Yao Cheng, Qi Hu, Jinxiang Ma, Qi Pan, Jian Shao, Kaixin Zhou

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引用次数: 0

Abstract

OBJECTIVE mtDNA 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 METHODS We 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. RESULTS A 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. CONCLUSIONS Blood mtDNA-CN showed a U-shaped association with incident type 2 diabetes in younger individuals.

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血液mtDNA拷贝数与2型糖尿病风险的u型关系

mtDNA拷贝数（CN）反映了线粒体功能，但之前的研究报道了与2型糖尿病风险不一致的关联，从负相关到阳性或无结果。我们假设mtDNA-CN与2型糖尿病发病率呈非线性相关。研究设计和方法我们纳入了来自昆山老龄化研究与电子健康（KARE）队列的34,835名无糖尿病成年人和来自英国生物银行（UKB）的289,338名成年人。使用Cox比例风险和按年龄分层的受限三次样条模型评估血液mtDNA-CN与2型糖尿病的关系。结果在KARE队列中观察到u形关联（P < 0.001），其中mtDNA-CN增加四分位数的风险比（95% ci）分别为1.00（参考）、0.94（0.88-1.00）、0.85（0.79-0.91）和0.93（0.87-1.00）。相比之下，UKB队列表现出主要的逆线性趋势。年龄分层分析显示，这种u型关联在年轻参与者（KARE年龄为65岁，UKB年龄为50岁）中尤为明显，表明mtDNA-CN水平高低都会增加糖尿病风险。此外，在两个队列中，mtDNA-CN随着年龄的增长而下降，在KARE中超过65岁，在UKB中超过50岁，mtDNA-CN下降加速。结论：血液mtDNA-CN与年轻人2型糖尿病发病率呈u型相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes Care 医学-内分泌学与代谢

CiteScore

27.80

自引率

4.90%

发文量

449

审稿时长

1 months

期刊介绍： The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes. Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.