1479-P: The Association between Race and Ethnicity and Type 2 Diabetes Is Partially Mediated by Circulating Proteins—A Meta-analysis of 2,339 Individuals from Two Multiethnic Cohorts of the TOPMed Program

It is critical to understand the molecular basis for well-recognized disparities in type 2 diabetes (T2D) risk. We aimed to examine plasma proteomic profile variations among self-identified racial and ethnic groups and assess the mediating impact of race- and ethnic-specific proteomic signatures on prevalent T2D.

Methods: We used proteomic data from 2339 individuals who self-identified as Non-Hispanic-White, Hispanic, or Non-Hispanic Black in the Women’s Health Initiative (N=1,400) and Multi-Ethnic Study of Atherosclerosis (N=939). To identify race- and ethnicity-specific associations we used linear models adjusting by confounders; site of recruitment, age, BMI, and eGFR. We employed structural equation modeling to examine the mediation by race and ethnic-specific proteins of the relationship between self-reported race/ethnicity and prevalent T2D. Models were stratified by sex, results were meta-analyzed and corrected for multiple comparisons (P<10^-5).

Results: We tested associations for 324 proteins. A total of 138 proteins (41.04%) were associated with self-reported race/ethnicity (P<10^-5). Seven proteins independently mediated the association between self-reported race/ethnicity and T2D (P<10^-6). Top significant proteins included Growth/differentiation factor 8, Insulin-like growth factor-binding protein 2, and Apolipoprotein M. We identified that 8-11% of the association between self-reported race and prevalent T2D can be attributed to the direct mediating effect of race-ethnic-specific proteomic signatures.

Conclusion: More than 40% of protein levels tested varied significantly by race and ethnicity. Seven protein levels were found to significantly mediate the association between race and ethnicity and T2D prevalence. These results provide insights into the molecular pathways that contribute to racial and ethnic disparities in T2D prevalence.