Gene-Lifestyle Interplay in Type 1 Diabetes: Joint Effects and Interactions From Cross-Sectional and Longitudinal Cohort Analyses

IF 6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes/Metabolism Research and Reviews Pub Date : 2026-04-15 DOI:10.1002/dmrr.70168

Chunran Lai, Qinyi Li, Xingchen Geng, Jiahui Cao, Xiaomin Zeng, Zijing Du, Shan Wang, Chenxiao Shen, Ying Fang, Yijun Hu, Xianwen Shang, Zhuoting Zhu, Xiayin Zhang, Honghua Yu

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Abstract

Background

Type 1 diabetes (T1D) is a complex autoimmune disorder heavily influenced by heritable traits. However, the interplay between modifiable lifestyle factors and genetic susceptibility remains insufficiently characterised. This study sought to elucidate how genetic background and lifestyle determinants jointly affect T1D liability.

Methods

Utilising the UK Biobank cohort, we performed both cross-sectional and longitudinal assessments. A polygenic risk score (PRS) was computed to quantify genetic predisposition to T1D across 403,778 subjects. Concurrently, a composite lifestyle index was generated based on six domains: adiposity, smoking status, alcohol intake, physical exertion, diet quality, and sleep duration. We evaluated cross-sectional relationships using multivariable logistic regression and assessed longitudinal outcomes using Cox proportional hazard models.

Results

In a 15-year longitudinal study (median follow-up: 12.3 years) of 402,005 participants, 1474 cases of T1D were identified. Stratified by genetic risk, participants in the intermediate (hazard ratio [HR] = 1.17; 95% CI: 1.00–1.37) and highest (HR = 2.89; 95% CI: 2.46–3.39) risk groups demonstrated significantly elevated risks of incident T1D compared to the lowest risk group, independent of lifestyle factors. Conversely, when categorised by lifestyle patterns, both intermediate (HR = 0.61; 95% CI: 0.52–0.71) and healthy (HR = 0.43; 95% CI: 0.37–0.52) lifestyle groups exhibited substantially reduced risks of T1D compared to the unhealthy lifestyle group, irrespective of genetic predisposition. A significant interaction between genetic risk and lifestyle on the risk of T1D was found in both cross-sectional and longitudinal analyses (p < 0.001).

Conclusions

The data reveal a robust inverse relationship between adherence to a healthy lifestyle and T1D incidence across all genetic strata, even among those with elevated hereditary risk. These results underscore the critical role of lifestyle modification in mitigating T1D susceptibility, distinct from genetic inheritance.

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基因-生活方式在1型糖尿病中的相互作用：来自横断面和纵向队列分析的联合效应和相互作用。

背景：1型糖尿病（T1D）是一种严重受遗传性状影响的复杂自身免疫性疾病。然而，可改变的生活方式因素和遗传易感性之间的相互作用仍然没有充分的特征。本研究旨在阐明遗传背景和生活方式决定因素如何共同影响T1D的发病风险。方法：利用英国生物银行队列，我们进行了横断面和纵向评估。计算多基因风险评分（PRS）来量化403,778名受试者的T1D遗传易感性。同时，根据肥胖、吸烟状况、饮酒、体力消耗、饮食质量和睡眠时间这六个方面，生成了一个复合生活方式指数。我们使用多变量逻辑回归评估横截面关系，并使用Cox比例风险模型评估纵向结果。结果：在一项为期15年（中位随访时间：12.3年）的402005名参与者的纵向研究中，发现了1474例T1D。根据遗传风险分层，与生活方式因素无关，中等风险组（风险比[HR] = 1.17; 95% CI: 1.00-1.37）和最高风险组（风险比[HR] = 2.89; 95% CI: 2.46-3.39）的参与者与最低风险组相比，T1D事件的风险显著升高。相反，当按生活方式分类时，无论遗传易感性如何，与不健康生活方式组相比，中等生活方式组（HR = 0.61; 95% CI: 0.52-0.71）和健康生活方式组（HR = 0.43; 95% CI: 0.37-0.52）患T1D的风险都大大降低。横断面和纵向分析均发现遗传风险和生活方式对T1D风险有显著的相互作用(p)。结论：数据显示，在所有遗传层中，即使在遗传风险较高的人群中，坚持健康的生活方式与T1D发病率之间存在显著的负相关关系。这些结果强调了生活方式改变在减轻T1D易感性方面的关键作用，这与基因遗传不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes/Metabolism Research and Reviews 医学-内分泌学与代谢

CiteScore

17.20

自引率

2.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.