Diabetes & Metabolism Journal

Original Articles

Metabolic Risk/Epidemiology
Birth Weight, Adult Fat Distribution, and Type 2 Diabetes Mellitus Risk: Sex-Specific Study in a Large Prospective Cohort: Ding Ding, Xiaoyi Luo, Shuhao Chen, Zhilin Liu, Xiaojing Kuang, Tianrui Zhuang, Gaoli She, Hailan Huang, Xingfen Yang, Jie Li, Ran An; Received June 29, 2025 Accepted October 23, 2025 Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0569 [Epub ahead of print]

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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.
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.
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.
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.

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Pancreatic fat and the risk of future dysglycemia: a systematic review and meta-analysis
Jie Yang, Xuan Zhang, Lihong Luo, Zhenjiang Zheng, Chunlu Tan, Xubao Liu, Yonghua Chen
The Journal of Clinical Endocrinology & Metabolism.2026;[Epub] CrossRef

Metabolic Risk/Epidemiology
Birth Weight, Cardiovascular Health, and Microvascular Complications in Individuals with Diabetes Mellitus: Chaolun Yu, Anping Feng, Xia Zou, Siqi Chen, Lingyan Dai, Qingmei Cui, Xiaojing Kuang, Gaoli She, Ying Ma, Haixia Guan, Jie Li; Diabetes Metab J. 2025;49(5):1075-1086. Published online May 23, 2025; DOI: https://doi.org/10.4093/dmj.2024.0518

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Background
Diabetes often leads to microvascular complications, including nephropathy, neuropathy, and retinopathy. Understanding the impact of early-life factors like birth weight and modifiable behaviors such as cardiovascular health (CVH) is essential for preventing these complications.
Methods
We included 11,515 participants with diabetes but without microvascular complications at baseline from the UK Biobank Study. CVH was evaluated using the Life’s Essential 8 score. Independent and joint associations of birth weight and CVH with microvascular complications were analyzed using Cox proportional hazard models. Two-sample Mendelian randomization (MR) analyses estimated unconfounded associations between birth weight and microvascular complications.
Results
Over a median follow-up of 13.1 years, 3,010 microvascular complications occurred. Compared with normal birth weight (2.5–4.0 kg), low birth weight (LBW; <2.5 kg) was associated with 15% higher risk of diabetic nephropathy (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.01 to 1.31), but not with neuropathy and retinopathy. High birth weight (>4.0 kg) was not associated with the risk of diabetic microvascular complications. MR analysis confirmed the association between LBW and nephropathy. Adherence to high CVH was associated with a reduced risk of microvascular complications compared to low CVH, regardless of birth weight. The HRs were 0.70 (95% CI, 0.59 to 0.84) for the LBW group and 0.74 (95% CI, 0.68 to 0.80) for the group with birth weight ≥2.5 kg (P for interaction=0.69).
Conclusion
LBW was an independent risk factor for nephropathy among diabetic patients. However, the detrimental effects of LBW might be mitigated by improvement in CVH.

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Predicting complications for diabetes in South Asians: Beyond convention
Beryl Lin, Lee-Ling Lim, Viswanathan Mohan, Jonathan E. Shaw
Best Practice & Research Clinical Endocrinology & Metabolism.2026; 40(4): 102119. CrossRef

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