Abstract P075: Genetic European Ancestry And Incident Diabetes Mellitus In Black Individuals-Insights From The SPRINT Trial

Abstract

Background: A metabolic paradox of lower triglyceride (TG) and higher high-density lipoprotein cholesterol (HDL-C) levels but a higher incidence of diabetes has been described in Blacks. We evaluated the association of genetic ancestry-related variants with the risk of incident diabetes in self-identified Black individuals in the Systolic Blood Pressure (BP) Intervention Trial (SPRINT). Methods: The genetic European ancestry proportions were estimated using 106 biallelic genotype markers in non-diabetic Black participants. Participants were stratified into tertiles (T1-T3) of European ancestry proportions. Multivariable-adjusted association of baseline metabolic syndrome indices (fasting plasma glucose [FPG], TG, HDL-C, body mass index [BMI], and BP) with the ancestry proportion was assessed. Multivariable-adjusted Cox regression was used to assess the risk of incident diabetes (FPG ≥126 mg/dL or self-reported diabetes treatment) across tertiles. Results: In 2,466 participants with median European ancestry 19% (13 - 27%), those in T1 were relatively younger, with lower Framingham risk score, and worse renal function (p<0.05 for all). At baseline, higher European ancestry proportion was associated with higher TG and lower HDL-C levels after controlling for clinical and demographic factors (p<0.05 for both). FPG, BMI, and BP were not significantly associated with ancestry proportion. Compared with T1, those in second (HR: 0.64 [95% CI: 0.45-0.90]) and third tertiles (HR: 0.61 [0.44-0.89]) had a lower risk of incident diabetes after controlling for covariates. Specifically, a 5% increment in European ancestry was associated with a 29% lower risk of incident diabetes (HR: 0.71 [0.55-0.93]). No interaction was observed between intensive BP control strategy and European ancestry proportion tertiles on incident diabetes. Conclusions: Genetic factors may account for racial differences in TG and HDL-C levels. The higher risk of incident diabetes in Blacks may similarly be genetically determined.