Plasma Proteomic Signatures of Adiposity Are Associated With Cardiovascular Risk Factors and Type 2 Diabetes Risk in a Multiethnic Asian Population

Abstract

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, includingmetabolically unhealthy obesity and type 2 diabetes incidence in the Singapore Multi-Ethnic Cohort Phase 1 (MEC1). Among 410 BMI-associated and 385 WCassociated 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 andWC 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.