Undiagnosed G6PD deficiency in Black and Asian individuals is prevalent and contributes to health inequalities in type 2 diabetes diagnosis and complications

<p dir="ltr">OBJECTIVE</p><p dir="ltr">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.</p><p dir="ltr">RESEARCH DESIGN AND METHODS</p><p dir="ltr">We used whole-exome sequencing and electronic health record data from UK Biobank (<i>n</i> = 467,368) and Genes & Health (<i>n</i> = 43,011) cohorts.</p><p dir="ltr">RESULTS</p><p dir="ltr">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 <i>G6PD</i> 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 <i>G6PD</i> 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 <i>G6PD</i> carriers falsely underestimated their 10‐year T2D risk.</p><p dir="ltr">CONCLUSIONS</p><p dir="ltr">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.</p>