| Title: | A U-Shaped Association Between Blood mtDNA Copy Number and Risk of Type 2 Diabetes. |
| Journal: | Diabetes Care |
| Published: | 16 Mar 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41837567/ |
| DOI: | https://doi.org/10.2337/dc25-2198 |
Publication 17370
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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.</p>
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.</p>
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.</p>
CONCLUSIONS: Blood mtDNA-CN showed a U-shaped association with incident type 2 diabetes in younger individuals.</p>
12 Authors
- Xinhao Huang
- Zijian Tian
- Ying Pan
- Jia Zhang
- Benrui Wu
- Shiteng Gao
- Yao Cheng
- Qi Hu
- Jinxiang Ma
- Qi Pan
- Jian Shao
- Kaixin Zhou
1 Application
| Application ID | Title |
|---|---|
| 902799 | Integrating modifiable, phenotypic, and multi-omics data to enhance the understanding of chronic non-communicable diseases |
Enabling scientific discoveries that improve human health