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 HbA1c for the prevailing glucose levels. Since HbA1c 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 UK. 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 UK, we estimated that approximately 1 in 7 Black and 1 in 63 Asian males carry G6PD deficiency alleles, compared to fewer than 1 in 10,000 White males. Despite this, less than 1 in 50 G6PD deficient men are clinically recognised. Male G6PD carriers have considerably lower average HbA1c (0.9% [IFCC: 10.0mmol/mol]) compared to non-carriers, 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 non-carriers. 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 to non-carriers. In addition, lower mean HbA1c values in G6PD carriers falsely under-estimated their 10-year T2D risk. Conclusions Undiagnosed G6PD deficiency has significant impact on T2D diagnosis with HbA1c and associates with increased risk of diabetes complications. This has major implications on global populations using HbA1c for diagnosis and monitoring, and could contribute significantly to inequalities in diabetes outcomes.