Table 2. Evaluation of Glycated Hemoglobin A_1c (HbA_1c) Performance: Greater Risk of False Positives Versus Greater Risk of False Negatives Among African Descent Populations Living in the United States, 2010–2019.

Study	HbA1c Evaluation Method	Findings	Performance
African American
1	Compared with other ethnic groups (ie, White people)	Main finding: Higher HbA1c values for African American than for White people at all fasting glucose levels (26).	Greater risk of false positives
		Additional findings: Relationship between HbA1c and simultaneous serum glucose did not differ between African American people with and without the SCT. SCT does not impact relationship between HbA1c and serum glucose concentration, and does not account for differences between African American and White people.
2	Compared with other ethnic groups (ie, White people)	Main finding: African American people without previous diagnosis of type 2 diabetes by OGTT had higher mean values of HbA1c than White people (β = 0.19% points; 95% CI = 0.14–0.24) (27).	Greater risk of false positives
		Additional finding: HbA1c values were compared for participants free of type 2 diabetes based on the OGTT.
3	Compared with other measures (ie, previous diagnosis)a	Main finding: Chronic financial strain increased sIL-6R, an inflammatory marker, and HbA1c (28).	Greater risk of false positives
		Additional finding: Although African American women had no previous prediabetes or type 2 diabetes diagnosis, 54% had HbA1c >5.7%.
4	Compared with other ethnic groups (ie, White people); Compared with other measures (ie, FPG and OGTT)	Main findings: For African American people (N = 408) classified as having normal glucose tolerance by either FPG or OGTT, HbA1c misclassified 3.5% of them as having type 2 diabetes (29). HbA1c diagnosed type 2 diabetes in 67% of African American people and 37.9% of White people.	Greater risk of false positives
5	Compared with other ethnic groups (ie, White people)	Main finding: HbA1c was higher in African American (mean [SD], 6.2% [0.6]) than in White people (mean [SD], 5.8% [0.4]) (30).	Greater risk of false positives
		Additional findings: Genomic analysis showed that 3 genetic factors contributed to the differences in HbA1c: PCA factor, SCT, and GRS. 60% of HbA1c differences between African American and White people are explained by first genomic PCA factor (degree of African ancestry). SCT explained 16% of the difference and GRS explained 14% of difference in HbA1c between African American and White people.
6	Compared with other measures (ie, OGTT)	Main findings: For patients with type 2 diabetes diagnosis by HbA1c, OGTT classified 48.3% with type 2 diabetes, 38.7% with IGT, and 12.9% with normal glucose tolerance. HbA1c ≤5.6% does not exclude type 2 diabetes or IGT. Among 33.7% of patients with HbA1c ≤5.6%, 64.3% had IGT or type 2 diabetes (31).	Greater risk of false positives at HbA1c ≥6.5% and greater risk of false negatives at HBA1c ≤5.6%
		Additional findings: 15.9% of patients had HbA1c ≥6.5%. HbA1c ≥6.5% indicates type 2 diabetes or IGT, with 50% sensitivity and 90% specificity. HbA1c ≥6.5% had positive predictive value of 48%. HbA1c ≤5.6% showed 17.2% sensitivity and 100% specificity.
7	Compared with other ethnic groups (ie, Hispanic and White people)	Main finding: Mean HbA1c levels were higher in African American (5.68%) than in Hispanic (5.57%) and White people (5.47%) (32).	Greater risk of false positives
		Additional findings: With every 1% increase in European ancestry, there was a 0.002% decrease in HbA1c. Individuals with 100% African American ancestry had an HbA1c value that was 0.27% higher than those with 100% European ancestry.
Afro-Caribbean
8	Compared with other measures (ie, FPG)	Main findings: At HbA1c ≥6.5%, sensitivity was 73% and specificity was 89%. At HbA1c ≥6.26%, sensitivity was 80% and specificity was 74% (33).	Greater risk of false negatives
		Additional finding: The area under the ROC curve for HbA1c as a diagnostic indicator of type 2 diabetes was 0.86.
African
9	Compared with other measures (ie, OGTT)	Main findings: For 32 individuals with type 2 diabetes, HbA1c detected type 2 diabetes in 32% and OGTT detected type 2 diabetes in 68% of individuals with HbA1c <6.5%. For 178 individuals with prediabetes, HbA1c detected prediabetes in 57% of individuals and OGTT detected prediabetes in 43% of individuals.	Greater risk of false negatives
		Additional finding: Using HbA1c alone missed a diagnosis of type 2 diabetes in 60% of African people and a prediabetes diagnosis in 40% of African people (34).
10	Compared with other measures (ie, FPG and OGTT)	Main finding: Among subjects with IGT by OGTT, HbA1c ≥5.7% had sensitivity of 53%, 54%, and 47% for the total, normal, and variant hemoglobin groups, respectively (35).	Greater risk of false negatives
		Additional findings: HbA1c with FPG demonstrated sensitivity of 64%. HbA1c diagnostic sensitivity did not vary by variant hemoglobin status.
11	Compared with other measures (ie, OGTT and glycated albumin)	Main finding: Among subjects with prediabetes by OGTT, HbA1c of 5.7% to less than 6.5% had 37% sensitivity in nonobese African immigrants and 64% sensitivity in obese African immigrants (36).	Greater risk of false negatives
		Additional finding: For HbA1c of 5.7% to less than 6.5% combined with glycated albumin ≥13.77%, sensitivity increased to 72% for nonobese African immigrants.
12	Compared with other measures (ie, OGTT and glycated albumin)	Main findings: When type 2 diabetes was detected by glycated plasma proteins (albumin or fructosamine; n = 24), average HbA1c was mean (SD) 5.2% (0.4). OGTT detected prediabetes in 74 individuals (13 of 74 had low HbA1c) (37).	Greater risk of false negatives
		Additional findings: HbA1c detected ≤50% of African immigrants with prediabetes. HbA1c combined with the glycated albumin test increases sensitivity to 80% for diagnosing prediabetes.

Abbreviations: OGTT, 2-hour oral glucose tolerance test; FPG, fasting plasma glucose; IGT, impaired glucose tolerance; PCA, principal component analysis; GRS, genetic risk score; SCT, sickle cell trait; ROC, receiver operating characteristic.

^a Exact temporality between the previous diagnosis and HbA_1c testing was not provided within the study, with an estimate of less than 12 months extrapolated from the study design. Findings from this study may represent new onset diabetes. This provides a limitation in the conclusive findings for HbA_1c performance in this study.