1331-P: Aggregate Effect of Hemoglobin A1c–Related Genetic Variants on Other Glycated Proteins by Ancestry

Introduction and Objective: Individuals who carry genetic variants that lower A1C independently of glycemia may have undetected hyperglycemia. Other glycated proteins can be used as alternate glycemic measures but whether these A1C variants affect their levels is unclear. Methods: We recalled 202 pa...

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Published inDiabetes (New York, N.Y.) Vol. 74; no. Supplement_1; p. 1
Main Authors THANGTHAENG, NOPPORN, MANDLA, RAVI, KARTIK, SAADHVI, FACIBENE, MARIELLA N., SAMPSON, MAUREEN, SACKS, DAVID B., MERCADER, JOSEP M., LEONG, AARON
Format Journal Article
LanguageEnglish
Published New York American Diabetes Association 20.06.2025
Subjects
Blood glucose
Diabetes mellitus
Discordance
Genetic diversity
Glucose
Glucose monitoring
Glucosephosphate dehydrogenase
Glycosylation
Hemoglobin
Hyperglycemia
Proteins
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Summary:Introduction and Objective: Individuals who carry genetic variants that lower A1C independently of glycemia may have undetected hyperglycemia. Other glycated proteins can be used as alternate glycemic measures but whether these A1C variants affect their levels is unclear. Methods: We recalled 202 patients (10% diabetes) from the Mass General Brigham Biobank enriching recruitment for the African Ancestry (AA) G6PD variant and tails of a European Ancestry (EA) polygenic score distribution comprising 123 variants reported in GWAS to affect A1C but not glucose. Subjects underwent 14 days of continuous glucose monitoring (CGM) and a blood draw measuring A1C, fructosamine (FRU), and glycated albumin (GA). We calculated A1C-Average Glucose (AG) discordance as measured A1C minus estimated-A1C from CGM-derived AG using the ADAG equation. Results: Despite similar or higher AG, GA, and FRU, A1C-AG discordance was lower in rs1050828 T allele carriers than AA noncarriers and lower in the bottom decile than the top decile of the EA polygenic score (all p ≤ 0.01, Table). A1C-AG discordance was higher and GA was higher in AA noncarriers than EA. Conclusion: Variants that lower A1C independently of glycemia, like the G6PD variant, do not appear to lower levels of other glycated proteins; yet both measured A1C and GA were higher in AA noncarriers than EA despite similar AG suggesting glycation propensity may differ by ancestry.
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ISSN:0012-1797
1939-327X
DOI:10.2337/db25-1331-P