1333-P: A Mutation Causing Glucose-6-Phosphate Dehydrogenase Deficiency Increases the Risk of Diabetes Complications in Men with African Ancestry

Prolonged hyperglycemia leads to diabetes complications, especially in individuals with African ancestry (AFR) - a health disparity. Glucose-6-phosphate dehydrogenase deficiency (G6PDd) disproportionately affects men with AFR ancestry (prevalence 9.5% vs. 2.2% in the US population) and shortens red cell lifespan, reducing HbA1c with no effect on glucose levels. We investigated whether men with AFR ancestry and G6PDd were at increased risk of diabetes complications. We performed a multi-ethnic genome-wide association study meta-analysis of diabetic retinopathy (DR) using the VA Million Veteran Program (MVP) dataset (nmax = 192,406) and studied clinical impact with the MVP and ACCORD trial datasets. Nine significant loci were associated with DR, including a causal variant for G6PDd [rs1050828-T, OR 1.48 (95% CI 1.45 - 1.51), p = 1.99x10-90)]. Plasma glucose was much higher in those with vs. without G6PDd in the year preceding diabetes diagnosis (168 vs. 137 mg/dL, respectively) and insulin prescription (253 vs. 233), both p