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Healthy diet and slower biological aging as protective factors against microvascular complications in type 2 diabetes

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This study aimed to evaluate the independent and joint effects of adherence to healthy dietary patterns and slower biological aging on the incidence of diabetic microvascular complications in individuals with type 2 diabetes mellitus (T2DM), and to assess the mediating role of biological aging. In a prospective cohort of 13,294 T2DM participants without baseline DMCs, dietary quality was assessed using a validated 10-point score, while biological aging was calculated from nine biomarkers and chronological age. Cox regression models were used to assess associations, and mediation analysis was performed to estimate the mediating effects of biological aging. Over a mean follow-up of 11.9 years, 3197 participants developed DMCs, including 1392 cases of diabetic retinopathy (DR), 1908 of diabetic nephropathy (DN), and 598 of diabetic neuropathy (DPN). Higher dietary scores (6–10) were associated with reduced risks of composite DMCs (HR 0.845; 95% CI 0.742–0.962), DR (0.804; 0.659–0.981), and DN (0.766; 0.643–0.911), but not DPN. Phenotypic age acceleration (PhenoAgeAccel) ≤ 0 was also linked to a reduced risk of DMCs. In addition, biologically younger with higher dietary score (6–10 points) had 39.4%, 30.8%, 53.6%, and 41.9% lower risk of composite DMCs, DR, DN, and DPN, respectively. Mediation analysis revealed that PhenoAgeAccel accounted for 43.0%, 29.8%, and 33.5% of the diet association with composite DMCs, DR, and DN, respectively. The results suggest that healthier dietary patterns and slower biological aging can reduce the risk of DMCs in T2DM patients, with a substantial portion of the dietary benefits mediated through slower aging. Integrating dietary and aging-targeted interventions may offer a promising method to reduce DMC risk in T2DM.

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Data availability

This study has been conducted using the UK Biobank Resource under Application Number 107451. The code, models, algorithms, protocols, methods, and other useful materials related to the project are available upon reasonable request to the corresponding authors.

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Acknowledgements

We are grateful to all the participants of UK Biobank and all the people involved in building the UK Biobank study.

Funding

This study was supported by the Shanghai Municipal Health Commission Collaborative Innovation Cluster Project (2024CXJQ02 to BY) and the Fundamental Research Funds for the Central Universities (YG2025ZD04 to BY and YG2025QNA43 to HZ).

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Author notes

  1. Han Zhou, Shuai Ben and Qian Ma contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200,080, China

    Han Zhou, Shuai Ben, Jiao Xia, XiongYi Yang, Qian Liu, Ya Zhao, Kun Liu & Biao Yan

  2. Department of Ophthalmology, General Hospital of Ningxia Medical University, Ningxia, 750,001, China

    Qian Ma & Na Li

  3. Department of Cardiac Surgery, Fuwai Hospital, Peking Union Medical College, Beijing, 100,044, China

    RuiKang Yang

  4. Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, 200,030, China

    Jing Li

  5. Department of Ophthalmology and Optometry, The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, 211,166, China

    JunYa Zhu

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Contributions

Study conception and design: H.Z, K.L, N.L, and B.Y; data curation: H.Z, S.B, Q.M, RK.Y, XY.Y, and J.L; formal analysis: H.Z, B.S, Q.M, and RK.Y; interpretation of data: Z.H, RK. Y, J.X, XY. Y, J.L, Q.L; writing: Z.H, S.B, Q.L, JY.Z, and Z.Y; reviewing: H.Z, Q.L, Z.Y, K.L, N.L, and B.Y. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Na Li, Kun Liu or Biao Yan.

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Not applicable. UK Biobank has full ethical approval from the NHS National Research Ethics Service (16/NW/0274). All participants gave written informed consent.

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The authors declare no competing interests.

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Zhou, H., Ben, S., Ma, Q. et al. Healthy diet and slower biological aging as protective factors against microvascular complications in type 2 diabetes. GeroScience (2025). https://doi.org/10.1007/s11357-025-02002-z

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