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To improve detection of undiagnosed diabetes in Africa, there is movement to replace the OGTT with A1C. The performance of A1C in the absence of hemoglobin-related micronutrient deficiencies, anemia and heterozygous hemoglobinopathies is unknown. Therefore, we determined in 441 African-born blacks living in America [male: 65% (281/441), age: 38 ± 10 y (mean ± SD), BMI: 27.5 ± 4.4 kg/m 2 ] (1) nutritional and hematologic profiles and (2) glucose tolerance categorization by OGTT and A1C.   Methods:  Hematologic and nutritional status were assessed. Hemoglobin <11 g/dL occurred in 3% (11/441) of patients and led to exclusion. A1C and OGTT were performed in the remaining 430 participants. ADA thresholds for A1C and OGTT were used. Diagnosis by A1C required meeting either A1C-alone or A1C&OGTT criteria. Diagnosis by OGTT-alone required detection by OGTT and not A1C.   Results:  Hemoglobin, mean corpuscular volume and red blood cell distribution width were 14.0 ± 1.3 g/dL, 85.5 ± 5.3 fL, and 13.2 ± 1.2% respectively. B12, folate, and iron deficiency occurred in 1% (5/430), 0% (0/430), and 4% (12/310), respectively. Heterozygous hemoglobinopathy prevalence was 18% (78/430). Overall, diabetes prevalence was 7% (32/430). A1C detected diabetes in 32% (10/32) but OGTT-alone detected 68% (22/32). Overall prediabetes prevalence was 41% (178/430). A1C detected 57% (102/178) but OGTT-alone identified 43% (76/178). After excluding individuals with heterozygous hemoglobinopathies, the rate of missed diagnosis by A1C of abnormal glucose tolerance did not change (OR: 0.99, 95% CI: 0.61, 1.62).   Conclusions:  In nutritionally replete Africans without anemia or heterozygous hemoglobinopathy, if only A1C is used, ~60% with diabetes and ~40% with prediabetes would be undiagnosed.   Clinical Trial Registration: :  www.ClinicalTrials.gov , Identifier: NCT00001853

frontiers in endocrinology

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