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

Diet affects the development of chronic diseases such as type 2 diabetes, but the underlying biological mechanisms are only partly understood. 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. 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 = 1878). These findings were validated in a Singapore Multi-Ethnic Cohort (n = 2395) 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. We identified 13 proteins consistently associated with the AHEI or DASH scores with the strongest associations for the AHEI score and epidermal growth factor receptor (β:0.089; SE: 0.017; q < 0.001) and for the DASH score and tissue factor (β: −0.114; SE: 0.022; q < 0.001). Most of these proteins were related to inflammation, thrombosis, adipogenesis, and glucose metabolism. Concentrations of myeloperoxidase, epidermal growth factor receptor, hepatocyte growth factor receptor, coagulation factor Xa, contactin 4, kynureninase, neurogenic locus notch homolog protein 1, and vesicular integral-membrane protein VIP36 were associated with the risk of type 2 diabetes in the Asian cohort. The diabetes odds ratio for a 2-fold higher protein abundance concentration ranged from 0.03 (95% CI: 0.01, 0.08) for neurogenic locus notch homolog protein 1 to 3.04 (95% CI: 2.13, 4.33) for kynureninase. Furthermore, genetic markers for myeloperoxidase and hepatocyte growth factor receptor were significantly associated with diabetes risk. 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.