The biomarkers connecting obesity and cardiometabolic diseases are not fully understood. We aimed to (i) evaluate the associations between body mass index (BMI), waist circumference (WC), and ∼5,000 plasma proteins (SomaScan v4), (ii) identify protein signatures of BMI and WC, and (iii) 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 (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of BMI and WC and validated them in an independent dataset across two timepoints 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 to 3.25) and ARIC (hazard ratio = 1.98, 95% CI 1.88 to 2.08). Our protein signatures have potential uses for the monitoring of metabolically unhealthy obesity.

中文翻译：

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肥胖的血浆蛋白质组学特征与多种族亚洲人群的心血管危险因素和 2 型糖尿病风险相关。


将肥胖与心脏代谢疾病联系起来的生物标志物尚不完全清楚。我们旨在 （i） 评估体重指数 （BMI）、腰围 （WC） 和 ∼5,000 血浆蛋白 （SomaScan v4） 之间的关联，（ii） 识别 BMI 和 WC 的蛋白质特征，以及 （iii） 评估蛋白质特征与心脏代谢健康之间的关联，包括代谢不健康的肥胖和新加坡多种族队列 （MEC1） 中的 2 型糖尿病发病率。在 410 种 BMI 相关蛋白和 385 种 WC 相关蛋白中，我们确定了 BMI 和 WC 的蛋白质特征，并在跨两个时间点的独立数据集中和社区动脉粥样硬化风险 （ARIC） 研究的外部数据集中对其进行了验证。BMI 和 WC 蛋白特征分别与总脂肪和内脏体脂高度相关。此外，蛋白质特征与心脏代谢危险因素和代谢不健康的肥胖显着相关。在前瞻性分析中，蛋白质特征与 MEC1 （WC 蛋白特征中每 SD 增量的比值比 = 2.84,95% CI 2.47 至 3.25） 和 ARIC （风险比 = 1.98,95% CI 1.88 至 2.08）中的 2 型糖尿病风险密切相关。我们的蛋白质特征在监测代谢不健康的肥胖方面具有潜在用途。