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

Charlie G. Lim, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Bige Ozkan, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Yujian Liang, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Jingsha Chen, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Jiali Yao, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Nang Ei Khaing, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Mary R. Rooney, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Chiadi E. Ndumele, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
E Shyong Tai, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Josef Coresh, Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Xueling Sim, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Rob M. van Dam, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.

Document Type

Journal Article

Publication Date

12-2-2024

Journal

Diabetes

DOI

10.2337/db24-0184

Abstract

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.

Department

Exercise and Nutrition Sciences

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