Lim Charlie G Y, Ozkan Bige, Liang Yujian, Chen Jingsha, Yao Jiali, Khaing Nang Ei Ei, Rooney Mary R, Ndumele Chiadi E, Tai E Shyong, Coresh Josef, Sim Xueling, van Dam Rob M
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
Diabetes. 2025 Mar 1;74(3):416-426. doi: 10.2337/db24-0184.
The biomarkers connecting obesity and cardiometabolic diseases are not fully understood. We aimed to 1) evaluate the associations between BMI, waist circumference (WC), and ∼5,000 plasma proteins (SomaScan V4), 2) identify protein signatures of BMI and WC, and 3) evaluate the associations between the protein signatures and cardiometabolic health, including metabolically unhealthy obesity and type 2 diabetes incidence in the Singapore Multi-Ethnic Cohort Phase 1 (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of BMI and WC and validated them in an independent data set across two time points and externally in the Atherosclerosis Risk in Communities (ARIC) study. The BMI and WC protein signatures were highly correlated with total and visceral body fat, respectively. Furthermore, the protein signatures were significantly associated with cardiometabolic risk factors and metabolically unhealthy obesity. In prospective analyses, the protein signatures were strongly associated with type 2 diabetes risk in MEC1 (odds ratio per SD increment in WC protein signature 2.84; 95% CI 2.47-3.25) and ARIC (hazard ratio 1.98; 95% CI 1.88-2.08). Our protein signatures have potential uses in the monitoring of metabolically unhealthy obesity.
We evaluated the associations between ∼5,000 plasma proteins and BMI and waist circumference (WC) in a multiethnic Asian population. We identified 410 proteins associated with BMI and 385 proteins associated with WC and derived protein signatures of BMI and WC, which we validated externally in a U.S. cohort. Both the BMI and WC protein signatures were strongly associated with cardiometabolic risk factors, metabolically unhealthy obesity, and risk of obesity, metabolic syndrome, and type 2 diabetes. Our protein signatures have potential uses in monitoring metabolically unhealthy obesity.
连接肥胖与心脏代谢疾病的生物标志物尚未完全明确。我们旨在：1）评估体重指数（BMI）、腰围（WC）与约5000种血浆蛋白（SomaScan V4）之间的关联；2）识别BMI和WC的蛋白特征；3）评估这些蛋白特征与心脏代谢健康之间的关联，包括新加坡多民族队列研究第一阶段（MEC1）中的代谢不健康肥胖和2型糖尿病发病率。在410种与BMI相关和385种与WC相关的蛋白中，我们识别出了BMI和WC的蛋白特征，并在两个时间点的独立数据集中以及在社区动脉粥样硬化风险（ARIC）研究中进行了外部验证。BMI和WC的蛋白特征分别与总体脂肪和内脏脂肪高度相关。此外，这些蛋白特征与心脏代谢风险因素和代谢不健康肥胖显著相关。在前瞻性分析中，这些蛋白特征与MEC1中2型糖尿病风险密切相关（WC蛋白特征每增加一个标准差，优势比为2.84；95%置信区间2.47 - 3.25）以及ARIC中（风险比为1.98；95%置信区间1.88 - 2.08）。我们的蛋白特征在监测代谢不健康肥胖方面具有潜在用途。
我们在一个多民族亚洲人群中评估了约5000种血浆蛋白与BMI和腰围（WC）之间的关联。我们识别出410种与BMI相关的蛋白和385种与WC相关的蛋白，并得出了BMI和WC的蛋白特征，我们在美国队列中进行了外部验证。BMI和WC的蛋白特征均与心脏代谢风险因素、代谢不健康肥胖以及肥胖、代谢综合征和2型糖尿病风险密切相关。我们的蛋白特征在监测代谢不健康肥胖方面具有潜在用途。
