Pitfalls in the use of HbA₁(c) as a diagnostic test: the ethnic conundrum

The purpose of a diagnostic test is to identify individuals who have a disorder and reassure those who do not. An HbA₁(c)-based diagnosis of diabetes mellitus or prediabetes fails to meet that purpose. Diabetes mellitus is a disorder of glucose, not HbA₁(c), metabolism. Microvascular complications in diabetes mellitus are driven by chronic hyperglycemia. The correlation of these complications with HbA₁(c) levels is convenient; however, unlike the direct information provided by glucose, HbA₁(c) values reflect glycemic and nonglycemic factors. The latter include modulators of glucose transport across the erythrocyte membrane, intracellular protein glycation and deglycation, erythrocyte turnover, systemic illness and hematological and medical disorders, among others. Genetic rather than glycemic factors explain most of the variance in HbA₁(c) levels. Finally, HbA₁(c) values are misleading as a measure of average blood glucose among persons of African, Asian, Hispanic and other non-European ancestry. Given the numerous pitfalls, the use of HbA₁(c) levels for diagnosing diabetes mellitus or prediabetes is ill-advised.