Proteomic analysis identifies novel biological pathways that may link dietary quality to type 2 diabetes risk: evidence from African American and Asian cohorts

Authors

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. Electronic address: clgy@nus.edu.sg.
Vlad Gradinariu, 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.
Yujian Liang, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
Casey M. Rebholz, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, Maryland 21205.
Sameera Talegawkar, Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, 6110 Executive Blvd, Suite 750 Rockville, MD, 20852.
Marinella Temprosa, Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, 6110 Executive Blvd, Suite 750 Rockville, MD, 20852.
Yuan-I Min, Department of Medicine, University of Mississippi Medical Center, Jackson Medical Mall, 350 West Woodrow Wilson Avenue, Jackson, MS 39213.
Xueling Sim, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549.
James G. Wilson, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215.
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; 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. Electronic address: rvandam@gwu.edu.

Document Type

Journal Article

Publication Date

11-18-2024

Journal

The American journal of clinical nutrition

DOI

10.1016/j.ajcnut.2024.11.016

Keywords

Alternative Healthy Eating Index; Dietary Approaches to Stop Hypertension; Dietary patterns; SomaScan; proteomics; type 2 diabetes

Abstract

BACKGROUND: Diet affects the development of chronic diseases such as type 2 diabetes, but the underlying biological mechanisms are only partly understood. OBJECTIVE: This study aimed to identify proteomic markers of the Alternative Healthy Eating Index (AHEI) and the Dietary Approaches to Stop Hypertension (DASH) diet and their association with type 2 diabetes risk. METHODS: We examined the associations between the AHEI and DASH diet quality scores and 1317 plasma proteins in African American participants of the Jackson Heart Study (JHS, N = 1,878). These findings were validated in a Singapore Multi-Ethnic Cohort (N = 2,395) and examined in relation to type 2 diabetes incidence (N = 539 cases). We adjusted for multiple testing by using False Discovery Rate-adjusted q-values. RESULTS: We identified 13 proteins consistently associated with the AHEI or DASH scores with the strongest associations for the AHEI score and EGFR (β = 0.089, SE = 0.017 q-value <0.001) and for the DASH score and F3 (β = -0.114, SE = 0.022, q-value <0.001). Most of these proteins were related to inflammation, thrombosis, adipogenesis, and glucose metabolism. Levels of MPO, EGFR, MET, F10, CNTN4, KNYU, NOTCH1, and LMAN2 were associated with the risk of type 2 diabetes in the Asian cohort. The diabetes odds ratio for a 2-fold higher protein abundance level ranged from 0.03 (95% CI: 0.01 to 0.08) for NOTCH1 to 3.04 (95% CI: 2.13 to 4.33) for KNYU. Furthermore, genetic markers for MPO and MET were significantly associated with diabetes risk. CONCLUSIONS: Our study across geographically and ethnically diverse populations identified robust protein biomarkers for healthy dietary patterns. Furthermore, our findings suggest novel biological mechanisms linking dietary patterns with type 2 diabetes development.

Department

Exercise and Nutrition Sciences

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