Undiagnosed G6PD Deficiency in Black and Asian Individuals Is Prevalent and Contributes to Health Inequalities in Type 2 Diabetes Diagnosis and Complications

OBJECTIVE Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents silently and is not routinely screened. It is associated with markedly lower HbA 1c for the prevailing glucose levels. Since HbA 1c is internationally recommended to diagnose and manage type 2 diabetes (T2D), we investigated the population-level impact of undiagnosed G6PD deficiency on T2D diagnosis and complications in the U.K. RESEARCH DESIGN AND METHODS We used whole-exome sequencing and electronic health record data from UK Biobank ( n = 467,368) and Genes & Health ( n = 43,011) cohorts. RESULTS In the U.K., we estimated that ∼1 in 7 Black and 1 in 63 Asian males carry G6PD deficiency alleles, compared with fewer than 1 in 10,000 White males. Despite this, less than 1 in 50 G6PD‐deficient men are clinically recognized. Male G6PD carriers have considerably lower average HbA 1c (0.9% [International Federation of Clinical Chemistry and Laboratory Medicine: 10.0 mmol/mol]) compared with noncarriers, while differences in average glucose were negligible. G6PD‐deficient men had 1.37 (95% CI: 1.01, 1.86) higher odds of developing diabetes‐related microvascular complications than noncarriers. Although risk factors were similar prior to diagnosis, male G6PD carriers diagnosed with T2D since 2011 were, on average, 4.1 years (95% CI: 0.6, 7.7) older at diagnosis compared with noncarriers. In addition, lower mean HbA 1c values in G6PD carriers falsely underestimated their 10‐year T2D risk. CONCLUSIONS Undiagnosed G6PD deficiency has significant impact on T2D diagnosis with HbA 1c and associates with increased risk of diabetes complications. This has major implications for global populations using HbA 1c for diagnosis and monitoring, and could contribute significantly to inequalities in diabetes outcomes.