Genetic predisposition to adiposity, and type 2 diabetes: the role of lifestyle and phenotypic adiposity.

IF 5.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

European Journal of Endocrinology Pub Date : 2025-04-30 DOI:10.1093/ejendo/lvaf084

Mengrong Zhang, Joey Ward, Rona J Strawbridge, Jana J Anderson, Carlos Celis-Morales, Jill P Pell, Frederick K Ho, Donald M Lyall

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引用次数: 0

Abstract

Aims: Genetic predisposition to adiposity is associated with type 2 diabetes (T2D), even in the absence of phenotypic adiposity (obesity and central obesity). We aimed to quantify the overall contribution of obesity and modifiable lifestyle factors to the association between genetic predisposition to adiposity and the development of T2D.

Methods: This prospective cohort study involved 220 703 White British participants from the UK Biobank. It examined the associations between genetic predisposition to adiposity [body mass index polygenic risk (BMI-PRS) and waist-hip ratio polygenic risk (WHR-PRS)] and incident T2D, as well as interactions and mediation via lifestyle factors (diet quality, physical activity levels, total energy intake, sleep duration, and smoking and alcohol intake) and phenotypic adiposity.

Results: People with high phenotypic adiposity and high adiposity PRS values (>1 SD above the mean) had the highest risk of incident T2D (versus non-obese/central obese and non-high PRS). This was the case for BMI-PRS [hazard ratio (HR) = 3.72] and WHR-PRS (HR = 4.17). Lifestyle factors explained 30.5% of the BMI-PRS/T2D association (2.0% mediation; 28.5% effect modification), and lifestyle and obesity together explained 92.1% (78.8% mediation; 13.3% effect modification). Lifestyle factors explained 20.4% of the WHR-PRS/T2D association (3.4% mediation; 17.0% effect modification), and lifestyle and central obesity together explained 72.8% (41.1% mediation; 31.7% effect modification).

Conclusions: Whilst phenotypic adiposity explains a large proportion of the association between BMI-PRS/WHR-PRS and T2D, modifiable lifestyle factors also make contributions. Promoting healthy lifestyles among people prone to adiposity is important in reducing the global burden of T2D.

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肥胖和2型糖尿病的遗传易感性：生活方式和表型肥胖的作用。

目的：即使在没有表型肥胖（肥胖和中心性肥胖）的情况下，肥胖的遗传易感性与2型糖尿病（T2D）有关。我们的目的是量化肥胖和可改变的生活方式因素对肥胖遗传易感性和T2D发展之间关系的总体贡献。方法：这项前瞻性队列研究涉及来自英国生物银行的220703名白人英国参与者。它研究了肥胖的遗传易感性[体重指数多基因风险（BMI-PRS）和腰臀比多基因风险（WHR-PRS）]与T2D事件之间的关联，以及生活方式因素（饮食质量、身体活动水平、总能量摄入、睡眠时间、吸烟和饮酒）与表型肥胖之间的相互作用和调解。结果：高表现型肥胖和高肥胖PRS值（>.1 SD高于平均值）的人发生T2D的风险最高（与非肥胖/中心性肥胖和非高PRS相比）。BMI-PRS[风险比(HR) = 3.72]和WHR-PRS （HR = 4.17）就是这种情况。生活方式因素解释了30.5%的BMI-PRS/T2D相关性(2.0%为中介；28.5%的影响修饰)，生活方式与肥胖共同解释92.1%(78.8%为中介；13.3%效果修正)。生活方式因素解释了20.4%的WHR-PRS/T2D相关性(3.4%为中介；17.0%影响修正)，生活方式与中心性肥胖共同解释72.8%(41.1%中介；31.7%效果修饰)。结论：虽然表型肥胖在BMI-PRS/WHR-PRS和T2D之间的关联中占很大比例，但可改变的生活方式因素也有贡献。在容易肥胖的人群中促进健康的生活方式对于减轻全球糖尿病负担非常重要。

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

European Journal of Endocrinology 医学-内分泌学与代谢

CiteScore

9.80

自引率

3.40%

发文量

354

审稿时长

1 months

期刊介绍： European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.