HbA1c Performance in African Descent Populations in the United States With Normal Glucose Tolerance, Prediabetes, or Diabetes

A Scoping Review

Lakshay Khosla, BA; Sonali Bhat, BA; Lee Ann Fullington, MPhil, MSLIS; Margrethe F. Horlyck-Romanovsky, DrPH

Disclosures

Prev Chronic Dis. 2021;18(3):e22 

In This Article

Discussion

We assessed 12 studies that evaluated the ability of HbA1c to correctly identify African American, Afro-Caribbean, and African people with prediabetes or type 2 diabetes. Studies among African American people found that HbA1c of 5.7% to less than 6.5% or HbA1c of 6.5% or higher led to overdiagnosis. In one study of Afro-Caribbean people, HbA1c of 6.5% or higher had a greater risk of false negatives (GRFN). Among African people, HbA1c of 5.7% to less than 6.5% or HbA1c of 6.5% or higher led to greater risk of underdiagnosis.

Overdiagnosis of diabetes was likely among African American people in 3 ways. African American people had consistently higher HbA1c levels than White people regardless of glycemic status.[26,27,29,30,32] Furthermore, half of normoglycemic African American people had HbA1c values greater than 5.7%;[28] and lastly, African American people were more likely to be diagnosed with type 2 diabetes by HbA1c of 6.5% or higher alone but not by OGTT.[29,31] Although study 6 did suggest a GRFN at HbA1c less than 5.7%, by misdiagnosing some participants as having normal glycemic status if their HbA1c was less than 5.7%,[31] the finding is limited by the smaller sample size of 83 participants when compared with the other studies. This finding must be investigated further.

In Afro-Caribbean people, the HbA1c cutoff of 6.5% is likely to result in underdiagnosis of type 2 diabetes because study 8 showed that more participants were correctly diagnosed as having type 2 diabetes if the cutoff was lowered to 6.26%.[33] However, this finding may not be generalizable to other Afro-Caribbean populations because of the smaller sample size and limitation of the study population to Haitian American people. Additionally, because only 1 study provided this conclusion, generalizability is further limited. For African people, underdiagnosis of prediabetes and type 2 diabetes is also likely at the standard HbA1c cutoffs because diagnosis was missed by HbA1c despite being detected by OGTT.[34–37] The findings among African people hold true regardless of hemoglobin variant or obesity status.[35,36]

Genetics are often thought to be responsible for the differences of HbA1c performance in African descent populations.[24,40–43] In fact, genetic analysis in study 5 shows that the HbA1c difference was primarily because of the genomic principal component analysis (PCA) factor in African American people when compared with White people.[30] The study demonstrated that the PCA factor was associated with increased HbA1c values in African American people. However, genetics do not fully explain HbA1c differences among African American people,[44] because increases in HbA1c may be mediated by social determinants of health (eg, chronic financial strain as seen in study 3) or chronic inflammation (sIL-6R).[28,45] Additionally, G6PD variant or deficiency is often correlated with lower HbA1c values in various populations,[40] especially in African American people and African people because of its higher prevalence in these groups.[14,46,47] Similarly, the sickle cell trait is associated with lower HbA1c values in African descent populations.[21,25] However, study 1 showed that the sickle cell trait may not actually correlate to changes in HbA1c values for African American people.[26] Findings regarding associations of genetics with HbA1c are still being researched in this population. Research accounting for genetically linked HbA1c differences in Afro-Caribbean people is also lacking. Genetic polymorphisms between African American people and Haitian people have been researched and show that differences in the PPARGC1A gene will correlate to risk of type 2 diabetes in African American people as opposed to protective associations with type 2 diabetes in Haitian people, suggesting that other genetic associations may explain differences in diabetes for Haitian people.[48] Although little research explains the role of genetics in HbA1c differences for Haitian people, one likely contributor to lower HbA1c values may be the G6PD variant because of its higher prevalence in populations of African descent.[47] Nevertheless, opposing findings regarding the role of genetics in influencing HbA1c values (eg, PCA factor is associated with higher HbA1c whereas the sickle cell trait is associated with lower HbA1c) make it difficult to ascertain the overall impact genetics has in causing the differences in HbA1c that were found for the African descent populations and therefore require further evaluation.

Socioeconomic factors and health behaviors such as diet, smoking, and exercise may explain some differences in glycemic control and HbA1c values among the 3 groups. Higher income and educational attainment appear to decrease the odds of diabetes among African immigrants, whereas only higher education lowers the odds for African American people.[5] Neither education nor income appear to affect diabetes risk among Afro-Caribbean people.[5,49] Additionally, study 3 found that financial stress and chronic inflammation were associated with higher HbA1c. Chronic inflammation resulting from social and environmental stressors, including experiences of racism, correlate to higher HbA1c in nondiabetic adults.[50] In terms of health behaviors, compared with African American people, African and Afro-Caribbean people are less likely to smoke. As African and Afro-Caribbean immigrants settle in the United States, they are affected by dietary acculturation often characterized by increased caloric intake and diets higher in refined carbohydrates, animal protein, fat, and sodium.[5] Although diet may affect glycemic control, it is unlikely that diet explains the differences in HbA1c performance illustrated in this study. These socioeconomic factors highlight the diversity of experience within African descent groups, which is often overshadowed by perceived homogeneity of the "Black" experience in the United States. Since immigration to the United States presents unique socioeconomic circumstances that can affect factors like HbA1c,[4] impacts of these circumstances are important to analyze distinctly from global concerns.

With these factors affecting HbA1c performance, results must be interpreted with caution. Some alternative diagnostic tests are suggested to aid or replace HbA1c for classification of glycemic status. For example, FPG in combination with HbA1c increases the sensitivity for type 2 diabetes diagnosis in African people (study 10).[35] A stronger relationship between HbA1c and FPG at higher FPG levels in most ethnic groups has been suggested as well.[51] Study 8 suggests that FPG may be a better measure of glycemic status than HbA1c in Afro-Caribbean people.[33] At the same time, studies 3, 6, and 9 through 12 suggest that OGTT more accurately measures glycemic status than HbA1c in both African American and African people.[28,31,34–37] Comparisons between HbA1c and OGTT in Afro-Caribbean people are lacking and should be studied further.

Convenient nonfasting alternatives for type 2 diabetes testing are other glycated proteins (eg, glycated albumin, fructosamine, and other advanced glycation end products) either in combination with or in place of HbA1c.[36,37,52–55] Although this approach is supported in multiethnic studies, these glycated proteins should be evaluated specifically in African descent groups.

Several limitations exist for the findings of our review. Despite constructing a comprehensive search, articles published in peer reviewed journals that were not indexed in PubMed, Scopus, and CINAHL may have been missed. The search contained nouns and adjectives as identification for African descent countries and regions of origin and HbA1c testing. However, study participant groups may be based on self or researcher categorization rather than actual region, country, or ethnic group of the participant. Findings must be interpreted with caution because of this subjective labeling within studies. Additionally, we did not use a specific protocol to evaluate the quality of the included studies, as this is not a part of scoping review methodologies and can increase risk of bias.[56,57] Another limitation that must be considered is that time may pass between HbA1c testing and alternate testing in some studies and glycemic status of individuals can change in that time; this limitation will usually exist in this nature of clinical research methodology and therefore must be recognized when evaluating the conclusions from those studies.

According to our review process, there is only 1 study protocol in the United States that examines performance of diabetes screening tests among African immigrants to the United States.[34–37] However, studies 9 through 12 demonstrate distinct comparisons within this cohort that illustrate significant conclusions about HbA1c performance. This is because the protocol is ongoing, and the number of participants increased over time. In turn, this also lends strength to the findings, because the similarity in protocol is balanced by the increasing diversity of the sample for each study design.

Finally, the lack of existing studies for Afro-Caribbean people in the United States presents a substantial limitation; our findings for this group must be interpreted cautiously. Further research is needed to understand the performance of HbA1c and evaluate alternate tests in place of the HbA1c in specific African descent populations, especially Afro-Caribbean people. Unique settings like New York City, where 32% of the African descent population is Afro-Caribbean and 4% is African,[58] may serve as key locations for public health researchers to investigate type 2 diabetes screening and diagnostics.

Our review also has several strengths. In partnership with our institution's research librarian, we tested several search constructions and selected the searches that provided the broadest selection within the scope of our topic. Additionally, we searched 3 databases without limiting article type or study designs on title and abstract review and had 2 reviewers independently screen the articles. This improved the selection of articles available for review and reduced selection bias. Finally, we were able to provide clear findings by constructing a label categorization scheme (GRFP/GRFN) that allowed for grouping of studies that used different comparative analytic and statistical methods to analyze HbA1c.

In African descent populations in the United States, the utility of HbA1c is limited in screening for glycemic status, determining care methods, assessing risk of type 2 diabetes complications, or analyzing health disparities. Current HbA1c cutoffs for prediabetes and type 2 diabetes may overestimate glycemic status in African American people and underestimate glycemic status in Afro-Caribbean and African people. Reasons for variations in HbA1c have been attributed to genetic, biochemical, and socioeconomic factors. Alternate testing such as OGTT, FPG, and other glycated blood proteins in place of or in combination with HbA1c may better assess glycemic status in African descent populations. Intraethnic HbA1c heterogeneity within the African descent groups must be recognized, and identification of more reliable type 2 diabetes screening and diagnostic tests is urgent.

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