Plasma proteomic signatures of adiposity are associated with cardiovascular risk factors and type 2 diabetes risk in a multi-ethnic Asian population

Abstract The molecular mechanisms connecting obesity and cardiometabolic diseases are not clearly understood. We evaluated the associations between body mass index (BMI), waist circumference (WC), and ∼5,000 plasma proteins 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 time points and externally in the Atherosclerosis Risk in Communities (ARIC) study. Among participants with more precise adiposity measurements, the BMI- and WC-protein signatures were highly correlated with total and visceral body fat, respectively. Both protein signatures were significantly associated with cardiometabolic risk factors. In prospective analyses, both protein signatures were strongly associated with type 2 diabetes (T2D) risk in both MEC1 and ARIC and explained the associations between anthropometric measurements and T2D risk. Our protein signatures have potential uses for the monitoring of metabolically unhealthy obesity and the changes therein during interventions.