{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:32:40Z","timestamp":1790742760016,"version":"4.1.0"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["Z01HG200362"],"award-info":[{"award-number":["Z01HG200362"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    G6PD deficiency (G6PD-D) variants are associated with lower hemoglobin A1c (HbA1c) concentrations, raising concerns about the diagnostic efficacy of HbA1c for abnormal glucose tolerance (Abnl-GT) in Africans, in whom risk of G6PD-D and Abnl-GT is high. G6PD-D is assessed using genotyping or an enzymatic assay, but because G6PD-D is X-linked, the enzymatic assay is necessary for determining status for women heterozygous for deficiency variants. We assessed: 1) ability of HbA1c to detect Abnl-GT by G6PD-D; 2) concordance of genotyping and enzymatic assay for G6PD-D in sub-Saharan Africans living in the US. 534 participants of the Africans in America study were included, with HbA1c ranging from 3.1\u201311.3%. Abnl-GT determined by HbA1c (\u22655.7%) was compared to the diagnostic standard, the oral glucose tolerance test (fasting glucose\u2265100 mg\/dL and\/or 2h glucose\u2265140 mg\/dL). G6PD-D status was determined by genotype (n\u2009=\u2009263), enzymatic assay (n\u2009=\u200983), or both (n\u2009=\u2009188). G6PD-D could not be determined for 13 women heterozygotes with only genotype data. In the remaining participants, HbA1c was 0.9% lower among those with G6PD-D (4.6\u2009\u00b1\u20090.5; range 3.1\u20135.6) compared to those with normal G6PD activity (5.5\u2009\u00b1\u20090.6; range 4.2\u201311.3;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Glucose concentrations did not differ between groups. HbA1c sensitivity and specificity for Abnl-GT were 0% (0\/17) and 100% (37\/37) among those with G6PD-D, and 50% (98\/195) and 80% (217\/272) among those with normal activity. After excluding women heterozygotes, concordance for G6PD-D detection by genotype and the enzymatic assay was 100%. G6PD-D was associated with ~0.9% lower HbA1c in this study, leading to a failure of HbA1c to identify Abnl-GT in these participants. Such a dramatic difference in a screening tool could have consequences in practice, including late diagnosis, undertreatment, and increased complications among those with G6PD-D. Additionally, the results for the enzymatic assay were perfectly concordant with the genotype results for G6PD-D. However, as genotype alone cannot predict G6PD-D in heterozygous women, the enzymatic assay was more informative.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0334634","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:27:45Z","timestamp":1769192865000},"page":"e0334634","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["HbA1c underperforms in identifying abnormal glucose tolerance in the presence of G6PD deficiency: Insight from the Africans in America study"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0827-9101","authenticated-orcid":true,"given":"Amy R.","family":"Bentley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-6535","authenticated-orcid":true,"given":"Kauthrah","family":"Ntabadde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine B.","family":"Kabeza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Ekoru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"DuBose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Sacks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adebowale A.","family":"Adeyemo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N.","family":"Rotimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"Sumner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"issue":"4","key":"pone.0334634.ref001","doi-asserted-by":"crossref","DOI":"10.1111\/dme.14754","article-title":"The diagnostic accuracy of HbA1c , compared to the oral glucose tolerance test, for screening for type 2 diabetes mellitus in Africa-A systematic review and meta-analysis","volume":"39","author":"T Chivese","year":"2022","journal-title":"Diabet Med"},{"issue":"9","key":"pone.0334634.ref002","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.2337\/dc19-0168","article-title":"A Genome-Wide Association Study Identifies Blood Disorder-Related Variants Influencing Hemoglobin A1c With Implications for Glycemic Status in U.S. Hispanics\/Latinos","volume":"42","author":"J-Y Moon","year":"2019","journal-title":"Diabetes Care"},{"issue":"4","key":"pone.0334634.ref003","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.ajhg.2019.08.010","article-title":"Impact of Rare and Common Genetic Variants on Diabetes Diagnosis by Hemoglobin A1c in Multi-Ancestry Cohorts: The Trans-Omics for Precision Medicine Program","volume":"105","author":"C Sarnowski","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"9","key":"pone.0334634.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002383","article-title":"Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis","volume":"14","author":"E Wheeler","year":"2017","journal-title":"PLoS Med"},{"key":"pone.0334634.ref005","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.15085","article-title":"Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia","volume":"6","author":"GM Clarke","year":"2017","journal-title":"Elife"},{"issue":"9606","key":"pone.0334634.ref006","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(08)60073-2","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"371","author":"MD Cappellini","year":"2008","journal-title":"Lancet"},{"key":"pone.0334634.ref007","doi-asserted-by":"crossref","first-page":"1393213","DOI":"10.3389\/fimmu.2024.1393213","article-title":"The global role of G6PD in infection and immunity","volume":"15","author":"SS Shah","year":"2024","journal-title":"Front Immunol"},{"key":"pone.0334634.ref008","doi-asserted-by":"crossref","first-page":"108918","DOI":"10.1016\/j.diabres.2021.108918","article-title":"Serum fructosamine and glycemic status in the presence of the sickle cell mutation","volume":"177","author":"AP Doumatey","year":"2021","journal-title":"Diabetes Res Clin Pract"},{"issue":"5","key":"pone.0334634.ref009","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1001\/jama.2016.20994","article-title":"Sickle Cell Trait and Interpretation of Hemoglobin A1c Levels","volume":"317","author":"AJ Bleyer","year":"2017","journal-title":"JAMA"},{"issue":"9","key":"pone.0334634.ref010","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1038\/s41591-024-03089-1","article-title":"Adaptive selection at G6PD and disparities in diabetes complications","volume":"30","author":"JH Breeyear","year":"2024","journal-title":"Nat Med"},{"key":"pone.0334634.ref011","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/1475-2875-10-241","article-title":"Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials","volume":"10","author":"N Carter","year":"2011","journal-title":"Malar J"},{"issue":"3","key":"pone.0334634.ref012","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/FPC.0000000000000456","article-title":"Incorporating G6PD genotyping to identify patients with G6PD deficiency","volume":"32","author":"SA Morris","year":"2022","journal-title":"Pharmacogenet Genomics"},{"key":"pone.0334634.ref013","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3389\/fendo.2019.00533","article-title":"A1C Underperforms as a Diagnostic Test in Africans Even in the Absence of Nutritional Deficiencies, Anemia and Hemoglobinopathies: Insight From the Africans in America Study","volume":"10","author":"SM Briker","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"10","key":"pone.0334634.ref014","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.2337\/dc20-1119","article-title":"Improved Detection of Abnormal Glucose Tolerance in Africans: The Value of Combining Hemoglobin A1c With Glycated Albumin","volume":"43","author":"AF Hobabagabo","year":"2020","journal-title":"Diabetes Care"},{"key":"pone.0334634.ref015","doi-asserted-by":"crossref","first-page":"108523","DOI":"10.1016\/j.diabres.2020.108523","article-title":"The OGTT is highly reproducible in Africans for the diagnosis of diabetes: Implications for treatment and protocol design","volume":"170","author":"R Jagannathan","year":"2020","journal-title":"Diabetes Res Clin Pract"},{"key":"pone.0334634.ref016","doi-asserted-by":"crossref","first-page":"111792","DOI":"10.1016\/j.diabres.2024.111792","article-title":"Determining the 1-hour post-load glucose which identifies diabetes in Africans: Insight from the Africans in America study","volume":"214","author":"CB Kabeza","year":"2024","journal-title":"Diabetes Res Clin Pract"},{"issue":"6","key":"pone.0334634.ref017","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/(SICI)1096-9136(199706)14:6<449::AID-DIA367>3.0.CO;2-D","article-title":"Diabetic retinopathy assessed by fundus photography in Pima Indians with impaired glucose tolerance and NIDDM","volume":"14","author":"DK Nagi","year":"1997","journal-title":"Diabet Med"},{"issue":"6","key":"pone.0334634.ref018","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41397-021-00242-8","article-title":"G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine\/hydroxychloroquine based treatments for COVID-19","volume":"21","author":"JEB da Rocha","year":"2021","journal-title":"Pharmacogenomics J"},{"issue":"2","key":"pone.0334634.ref019","article-title":"Evidence of positively selected G6PD A- allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island","volume":"8","author":"X-Y Liang","year":"2020","journal-title":"Mol Genet Genomic Med"},{"issue":"11","key":"pone.0334634.ref020","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/ng.3107","article-title":"Reappraisal of known malaria resistance loci in a large multicenter study","volume":"46","author":"Malaria Genomic Epidemiology Network, Malaria Genomic Epidemiology Network","year":"2014","journal-title":"Nat Genet"},{"issue":"10","key":"pone.0334634.ref021","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3026(15)00152-0","article-title":"Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study","volume":"2","author":"S Uyoga","year":"2015","journal-title":"Lancet Haematol"},{"issue":"19","key":"pone.0334634.ref022","doi-asserted-by":"crossref","first-page":"8568","DOI":"10.1073\/pnas.88.19.8568","article-title":"Polymorphic sites in the African population detected by sequence analysis of the glucose-6-phosphate dehydrogenase gene outline the evolution of the variants A and A-","volume":"88","author":"TJ Vulliamy","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7571","key":"pone.0334634.ref023","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"1000 Genomes Project Consortium","year":"2015","journal-title":"Nature"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:27:49Z","timestamp":1769192869000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334634"}},"subtitle":[],"editor":[{"given":"Germana","family":"Bancone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0334634","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}