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

Abstract

Introduction: 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

The OGTT is highly reproducible in Africans for the diagnosis of diabetes: Implications for treatment and protocol design

“…of access to care [1]. However, failure of fasting plasma glucose (FPG) and HbA 1c , to detect early T2D in Africans must be considered [3,4]. As early T2D in Africans often occurs with only a 2 h glucose (2 h-PG) 11.1 mmol/L, performance of an OGTT is pivotal [4,5].…”

The Sickle Effect: The Silent Titan Affecting Glycated Hemoglobin Reliability

“…Briker et al also found similar disparities in the African population [12]. Using HbA1c as the sole diagnostic tool in nutritionally replete Africans without anemia or heterozygous hemoglobinopathy would underdiagnose 60% of diabetics and 40% of prediabetics.…”

“…However, 11 studies showed that using an NGSP-certified machine without HbS interference gave conflicting results, as seen in Table 3. One study stated that HbA1c was higher [4], three stated the same [3,12,16], five stated lower [5,6,11,14,17], one stated higher to lower [13], and one stated the same to lower [15], when compared to a hematologically normal patient.…”

“…These studies showed some limitations: lack of checking for alpha thalassemia [5], low frequency of SCT patients [3,4,6,12], and basing the analysis on a single determination such as oral glucose tolerance test (OGTT) [4], fasting plasma glucose (FPG), or HbA1c [3]. Lack of HbS percentages [14] and exclusion of participants, who may have SCT from the analysis process [6], due to missing data of SCT status may contribute to the differences in results obtained.…”

Metabolic characteristics of Africans with normal glucose tolerance and elevated 1-hour glucose: insight from the Africans in America study

“…The Africans in America cohort was established to assess risk for diabetes and heart disease in African-born blacks living in the USA 20 21. Recruitment was by newspaper advertisements (45%), participant referrals (30%), presentations at community events, flyers and electronic outreach.…”