Why did we do this research?
GWAS have reported over 200 hemoglobin A1c (HbA1c)-associated genetic variants, the majority of which affect HbA1c levels independently of glucose. Individuals who carry these nonglycemic HbA1c variants may have undetected hyperglycemia if HbA1c is used to diagnose diabetes or estimate glycemic control.
What were the aims of this research?
- To estimate the effects of nonglycemic HbA1c variants on HbA1c-glucose discordance and glycated proteins by assessing the difference between measured and predicted HbA1c by 10-14 days of continuous glucose monitoring, and collecting albumin and fructosamine measurements
- To use recall-by-genotype for enriched recruitment of subjects with African or European ancestry
What were the outcomes?
- In all genotype groups, HbA1c was well correlated with CGM glucose, but the HbA1c-glucose relationship differed by G6PD genotype, polygenic score, and ancestry
- HbA1c-glycemia discordance differed among those with European ancestry based on polygenic score and among those with African ancestry based on whether or not they are G6PD carriers
- HbA1c and glycated albumin were higher in individuals with African ancestry compared to European ancestry, despite similar CGM glucose, suggesting glycation propensity may differ by ancestry