Soluble receptor for advanced glycation end products and diabetes in Black and White Americans: the REGARDS Study

Diabetes is a leading cause of morbidity and mortality in the United States, affecting Black more than White adults. The soluble receptor for advanced glycation end products (sRAGE) prevents signaling that induces inflammation and is implicated in diabetes pathogenesis. This analysis investigated if low sRAGE is associated with diabetes risk, and if sRAGE mediates the racial disparity in diabetes.

The REasons for Geographic and Racial Differences in Stroke prospective cohort included 30,239 Black and White adults aged ≥45 with baseline and follow up exam. We studied a 4,400 participant sub-cohort with 9.5-year follow-up to classify diabetes, with analyses being survey weighted to the larger cohort. Baseline sRAGE was measured in 3,400 at risk for diabetes; modified Poisson regression estimated relative risk (RR) by sRAGE. Inverse odds weighting mediation analysis examined the contribution of sRAGE to the racial disparity in diabetes.

Ten percent of White and 18% of Black participants experienced incident diabetes. The RR of diabetes was elevated in lower quartiles of sRAGE compared to the fourth quartile. With diabetes risk factor adjustment, the RR was 1.32 (95% CI 0.97-1.79) in the lowest compared to the highest quartile (p-trend across quartiles 0.06). sRAGE did not mediate any of the racial disparity in diabetes.

Among Black and White Americans, low sRAGE was associated with increased risk of developing diabetes; associations attenuated and became non-significant with covariate adjustment. sRAGE may serve as a marker for diabetes risk, but clinical utility is unlikely given small non-significant associations, and no identified mediation of the association by sRAGE.