Association of a composite trait for anthropometrics, adiposity and energy expenditure with cardiometabolic diseases: An age-stratified cohort and genetic risk score analysis

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes, Obesity & Metabolism Pub Date : 2024-10-02 DOI:10.1111/dom.15966

Fleur L. Meulmeester MSc, Ko Willems van Dijk, Diana van Heemst, Raymond Noordam

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Abstract

Aim

Various anthropometric measures capture distinct as well as overlapping characteristics of an individual's body composition. To characterize independent body composition measures, we aimed to reduce easily-obtainable individual measures reflecting adiposity, anthropometrics and energy expenditure into fewer independent constructs, and to assess their potential sex- and age-specific relation with cardiometabolic diseases.

Methods

Analyses were performed within European ancestry participants from UK Biobank (N = 418,963, mean age 58.0 years, 56% women). Principal components (PC) analyses were used for the dimension reduction of 11 measures of adiposity, anthropometrics and energy expenditure. PCs were studied in relation to incident type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). Multivariable-adjusted Cox regression analyses, adjusted for confounding factors, were performed in all and stratified by age. Genome-wide association studies were performed in half of the cohort (N = 156,295) to identify genetic variants as instrumental variables. Genetic risk score analyses were performed in the other half of the cohort stratified by age of disease onset (N = 156,295).

Results

We identified two PCs, of which PC1 reflected lower overall adiposity (negatively correlated with all adiposity aspects) and PC2 reflected more central adiposity (mainly correlated with higher waist–hip ratio, but with lower total body fat) and increased height, collectively capturing 87.8% of the total variance. Similar to that observed in the multivariable-adjusted regression analyses, we found associations between the PC1 genetic risk score and lower risks of CAD and T2D [CAD cases <50 years, odds ratio: 0.91 (95% confidence interval 0.87, 0.94) per SD; T2D cases <50 years, odds ratio: 0.76 (0.72, 0.81)], which attenuated with higher age (p-values 8.13E-4 and 2.41E-6, respectively). No associations were found for PC2.

Conclusions

The consistently observed weaker associations of the composite traits with cardiometabolic disease suggests the need for age-specific cardiometabolic disease prevention strategies.

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人体测量、脂肪和能量消耗的复合特征与心脏代谢疾病的关系：年龄分层队列和遗传风险评分分析。

目的：各种人体测量指标可以捕捉到个人身体成分的不同特征和重叠特征。为了描述独立的身体成分测量指标的特征，我们旨在将易于获得的反映脂肪率、人体测量和能量消耗的个体测量指标简化为较少的独立结构，并评估它们与心脏代谢疾病的潜在性别和年龄特异性关系：分析对象为英国生物库中的欧洲血统参与者（N = 418,963 人，平均年龄 58.0 岁，56% 为女性）。采用主成分（PC）分析法对 11 项脂肪含量、人体测量和能量消耗指标进行降维处理。研究了 PC 与 2 型糖尿病（T2D）和冠状动脉疾病（CAD）的关系。在对混杂因素进行调整后，对所有人进行了多变量调整 Cox 回归分析，并按年龄进行了分层。对半数队列（N = 156,295 人）进行了全基因组关联研究，以确定作为工具变量的遗传变异。在另一半队列中按发病年龄进行了遗传风险评分分析（N = 156 295）：我们发现了两个 PC，其中 PC1 反映了较低的总体脂肪率（与所有脂肪率方面均呈负相关），PC2 反映了较高的中心脂肪率（主要与较高的腰臀比相关，但与较低的总体脂肪率相关）和较高的身高，共占总变异的 87.8%。与多变量调整回归分析中观察到的情况类似，我们发现 PC1 遗传风险评分与较低的 CAD 和 T2D 风险之间存在关联（CAD 病例结论）：综合特征与心血管代谢疾病的关联性一直较弱，这表明需要制定针对特定年龄段的心血管代谢疾病预防策略。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.