Introduction and Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, characterized by a shortened erythrocyte lifespan, can affect HbA1c levels and may be associated with health outcomes in patients with diabetes. We investigated the association of G6PD risk genotype and G6PD protein levels with diabetic kidney disease (DKD) progression in the Chronic Renal Insufficiency Cohort (CRIC). Methods: We included 1619 CRIC participants with diabetes and available genotyping (Illumina HumanOmni1-quad) and proteomics (SomaScan). DKD progression was defined as ≥ 50% eGFR decline or end-stage kidney disease. Associations were evaluated using Cox regression and G6PD protein levels modeled as restricted cubic splines and quartiles, adjusted for clinical covariates. Results: Lower G6PD protein and G6PD T alleles were associated with lower HbA1c (Table, C). During a mean follow-up of 6 years, there were 649 cases of DKD progression. Each copy of the G6PD T allele increased the risk of DKD progression (HR=1.31, 95% CI: 1.10-1.57, Ptrend=0.003). Lower G6PD protein levels were associated with increased risk of DKD progression (Figure, A, Poverall 0.0001, Plinearity 0.0001), with an HR of 1.46 (95% CI: 1.23-1.72) in Q1 (vs Q2-Q4). Results for G6PD protein were similar in Black and White adults. Conclusion: Both the G6PD risk genotype and lower G6PD protein levels were associated with elevated risk of DKD progression. Disclosure X. Li: None. X. Sun: None. A.H. Anderson: None. C. Rebholz: None. E. Selvin: Other - In 2025, Dr. Selvin received payment for an educational webinar (content her own) sponsored by Siemens Healthineers and hosted by the Association for Diagnostics Ended; Siemens. J. Lash: None. A. Ricardo: None. B. Layden: None. T. Kelly: None. Funding American Heart Association (25CDA1447844)
LI et al. (Fri,) studied this question.