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

Charlie G Y Lim; Bige Ozkan; Yujian Liang; Jingsha Chen; Jiali Yao; Nang Ei Ei Khaing; Mary R Rooney; Chiadi E Ndumele; E Shyong Tai; Josef Coresh; Xueling Sim; Rob M van Dam

doi:10.2337/db24-0184

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

Diabetes. 2024 Dec 2:db240184. doi: 10.2337/db24-0184. Online ahead of print.

Authors

Charlie G Y Lim¹, Bige Ozkan^{2

3}, Yujian Liang¹, Jingsha Chen², Jiali Yao¹, Nang Ei Ei Khaing¹, Mary R Rooney², Chiadi E Ndumele^{2

3}, E Shyong Tai^{1

4}, Josef Coresh², Xueling Sim¹, Rob M van Dam^{1

5}

Affiliations

¹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
² Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
³ Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore 117597.
⁵ Departments of Exercise and Nutrition Sciences and Epidemiology, Milken Institute School of Public Health, The George Washington University, 950 New Hampshire Ave, NW, Washington, DC 20052.

PMID: 39621883
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.