| Title: | Birth Weight, Adult Fat Distribution, and Type 2 Diabetes Mellitus Risk: Sex-Specific Study in a Large Prospective Cohort |
| Journal: | Diabetes & Metabolism Journal |
| Published: | 29 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41605138/ |
| DOI: | https://doi.org/10.4093/dmj.2025.0569 |
| URL: | https://www.e-dmj.org/upload/pdf/dmj-2025-0569.pdf |
Publication 18428
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Abstract
Background: Regional fat distribution is a key determinant of metabolic risk, independent of total adiposity. However, the developmental origins of fat depot-specific accumulation and its contribution to type 2 diabetes mellitus (T2DM) remain unclear. We aimed to investigate whether adult fat distribution mediates the association between birth weight (BW) and T2DM risk.</p>
Methods: We analyzed 30,718 diabetes-free UK Biobank participants with magnetic resonance imaging/dual-energy X-ray absorptiometry derived measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and gynoid adipose tissue (GAT), liver fat fraction (LFF), pancreatic fat fraction (PFF), and muscle fat infiltration (MFI). Fat depots were adjusted for body mass index (BMI) using sex-specific residuals. Cox regression assessed associations of BW and fat depots with T2DM risk. Mediation analysis assessed indirect effects of fat distribution.</p>
Results: Lower BW was associated with a higher risk of T2DM (hazard ratio per 1 kg increase, 0.71; 95% confidence interval, 0.64 to 0.79), with stronger effects in women. Lower BW was linked to greater VAT, LFF, and PFF, and lower GAT, independent of BMI. Higher levels of VAT, LFF, and PFF were associated with increased T2DM risk, while GAT was protective. Mediation analysis revealed that fat distribution partially mediated the BW-T2DM relationship, with LFF showing the strongest mediation effect (11%). Mediation patterns differed by sex: LFF and VAT were the predominant mediators in women, while LFF and GAT contributed substantially in men.</p>
Conclusion: Fat distribution-particularly liver and visceral fat-partially mediates the BW-T2DM relationship, independent of BMI. These findings highlight the clinical importance of fat depot profiling in understanding the developmental origins of diabetes and guiding early risk stratification.</p>
11 Authors
- Ding Ding
- Xiaoyi Luo
- Shuhao Chen
- Zhilin Liu
- Xiaojing Kuang
- Tianrui Zhuang
- Gaoli She
- Hailan Huang
- Xingfen Yang
- Jie Li
- Ran An
1 Application
| Application ID | Title |
|---|---|
| 98937 | Shared and distinct mechanisms between mental disorders and noncommunicable chronic diseases: prevention, risk prediction and precision treatment |
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