Zhang Ziteng, Wang Junxue, Yu Bowei, Sun Ying, Chen Yi, Lu Yingli, Wang Ningjian, Xia Fangzhen
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
J Endocrinol Invest. 2025 Feb;48(2):435-443. doi: 10.1007/s40618-024-02436-w. Epub 2024 Oct 3.
Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids.
This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids.
During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM.
Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.
衰老在2型糖尿病（T2DM）中起重要作用。但加速生物衰老与T2DM之间的关联以及这种关联的潜在机制仍不清楚。因此，本研究旨在探讨生物衰老与T2DM的关联，并探索氨基酸的潜在中介作用。
这项前瞻性队列研究纳入了英国生物银行的95773名参与者，他们在基线时无糖尿病。使用PhenoAgeAccel从临床特征测量生物年龄。采用Cox比例风险模型估计风险比（HRs）和95%置信区间（CIs），并采用中介分析来探索氨基酸的中介作用。
在中位随访14.02年期间，记录了6347例新发T2DM病例。在对社会人口学特征、生活方式因素和其他T2DM风险因素进行多变量调整后，生物年龄较大的参与者发生新发T2DM的风险增加（PhenoAgeAccel每增加一个标准差，风险增加30%，95%CI：28.0 - 33.0%）。此外，包括异亮氨酸和亮氨酸在内的较高支链氨基酸（BCAAs）、包括苯丙氨酸和酪氨酸在内的芳香族氨基酸（AAAs）与PhenoAgeAccel增加和新发T2DM风险增加相关；而谷氨酰胺和甘氨酸则呈负相关。丙氨酸、谷氨酰胺、甘氨酸、苯丙氨酸、酪氨酸、异亮氨酸、亮氨酸和支链氨基酸的总浓度可部分解释PhenoAgeAccel与T2DM之间的关联。
加速生物衰老与新发T2DM风险增加相关，独立于实际年龄，可能是T2DM的一个风险因素，部分由几种氨基酸介导。
