Introduction and Objective: Glycated hemoglobin (HbA1c) is the primary clinical measure of average glucose (AG). The X-linked G6PD variant has been associated with lower HbA1c but higher complication risks; yet the extent to which the variant impacts the HbA1c-AG relationship resulting in undetected hyperglycemia is unclear.Methods: In the GRADE Study, 1287 participants with type 2 diabetes including 303 non-Hispanic Blacks (NHB) underwent 10 days of continuous glucose monitoring (CGM) followed by HbA1c and glycated albumin (GA) measurements. By linear regression, we compared CGM-derived AG with HbA1c and GA.Results: Median HbA1c (~6.8%) was similar across G6PD genotypes but AG was higher in rs1050828 T-allele carriers (T, men: 160 mg/dL; CT, women: 126 mg/dL) than NHB noncarriers (CC, men: 123 mg/dL; women: 119 mg/dL). The regression slopes and intercepts of AG on HbA1c differed by race and genotype yet the relationship with GA was similar by genotype (Figure). For a predicted HbA1c of 7%, AG in hemizygous men was 25 mg/dL higher than heterozygous women, 44 mg/dL higher than noncarriers, and 12 mg/dL higher than AG calculated from regression equations used in clinical practice to convert HbA1c to AG.Conclusion: The relationship between AG and HbA1c differed by G6PD genotype and race. Using genotype specific regression equations, GA or CGM could reduce undetected hyperglycemia in diverse populations.
A. Leong: Other Relationship; Merck & Co., Inc. M. Tripputi: None. L. Szczerbinski: None. S. Rosin: None. A.J. Kretowski: None. J.M. Mercader: None. N. Younes: None. J.H. Li: None. J.C. Florez: Research Support; Novo Nordisk.
The National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246; U34-DK-088043); American Diabetes Association (7-22-ICTSPM-23); The National Heart Lung, and Blood Institute; The Centers for Disease Control and Prevention
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