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

Authors

Charlie G. Lim, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Bige Ozkan, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
Yujian Liang, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Jingsha Chen, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
Jiali Yao, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Nang Ei Khaing, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Mary R. Rooney, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
Chiadi E. Ndumele, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
E Shyong Tai, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Josef Coresh, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
Xueling Sim, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Rob M. van Dam, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

Document Type

Journal Article

Publication Date

3-1-2025

Journal

Diabetes

Volume

74

Issue

3

DOI

10.2337/db24-0184

Abstract

UNLABELLED: 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. ARTICLE HIGHLIGHTS: 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.

APA Citation

Lim, Charlie G.; Ozkan, Bige; Liang, Yujian; Chen, Jingsha; Yao, Jiali; Khaing, Nang Ei; Rooney, Mary R.; Ndumele, Chiadi E.; Tai, E Shyong; Coresh, Josef; Sim, Xueling; and van Dam, Rob M., "Plasma Proteomic Signatures of Adiposity Are Associated With Cardiovascular Risk Factors and Type 2 Diabetes Risk in a Multiethnic Asian Population" (2025). GW Authored Works. Paper 6946.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6946

Department

Exercise and Nutrition Sciences