https://diabetes.acponline.org/archives/2017/02/10/2.htm

Sickle cell trait affects HbA1c's accuracy as a measure of glycemia, study finds

Mean HbA1c was 5.7% in the African-American participants with sickle cell trait and 6.0% in those without, despite similar mean fasting and two-hour glucose values.


Patients with sickle cell trait (SCT) may have lower HbA1c levels than those without SCT who have similar fasting and two-hour glucose measures.

Researchers retrospectively pooled data from 4,620 participants who self-identified as African American in two community-based cohorts, the Coronary Artery Risk Development in Young Adults study (1,572 participants) and the Jackson Heart Study (3,048 participants). A total of 367 participants (7.9%) had SCT.

Using 9,062 concurrent measures of HbA1c and fasting glucose and 2,001 concurrent measures of HbA1c and two-hour glucose measures, researchers examined the association between HbA1c and SCT, adjusting for fasting or two-hour glucose measures. Results were published online on Feb. 7 by JAMA.

Mean HbA1c was 5.7% in participants with SCT and 6.0% in those without SCT, despite similar mean fasting (103.0 vs. 102.9 mg/dL [5.722 vs. 5.716 mmol/L]; P=0.88) and two-hour glucose values (118.5 vs. 113.0 mg/dL [6.58 vs. 6.28 mmol/L]; P=0.19) for those with versus without SCT, respectively. Mean HbA1c values were lower in participants with SCT than those without SCT across all categories of fasting and two-hour glucose measures.

After adjusting for various confounders, researchers found that HbA1c values remained significantly lower in participants with SCT versus those without SCT (mean HbA1c difference, −0.32%; 95% CI, −0.38% to −0.26%; P<0.001). They also found that the difference in HbA1c by SCT status was greater at higher concentrations of both fasting glucose (P=0.02 for interaction in unadjusted analyses; P=0.01 in adjusted analyses) and two-hour glucose (P=0.03 for interaction in both unadjusted and adjusted analyses).

Using standard clinical HbA1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with SCT compared with those without SCT, whereas glucose-based methods resulted in a similar prevalence regardless of SCT status, the study authors noted. Limitations of the study include the relatively small number of participants who had SCT and the lack of clinical outcomes assessed.

An accompanying editorial noted that it seems to be beneficial for black patients with diabetes to be tested for SCT and have their results documented in the medical record. “It is imperative to determine whether racial differences in the HbA1c-to-glucose relationship exist, to incorporate this information when specifying treatment targets, and to consider these issues when designing clinical trials,” the editorialists wrote. “An estimated mean glucose concentration that considers factors such as age, race, ancestry, iron deficiency, and other factors might prove to be a more useful tool for diagnosing and managing diabetes mellitus than HbA1c concentration.” The editorialists went on to suggest clinicians not rely strictly on the HbA1c in black patients with SCT but consider performing an oral glucose tolerance test.

A relevant viewpoint article published online on Jan. 26 by JAMA questioned the reliance on HbA1c as a primary efficacy endpoint in drug trials. “Trials that use outcomes based solely on glycemic parameters are no longer acceptable for clinical decision making,” the viewpoint stated. “Clinicians and patients need evidence about outcomes associated with different drug classes and likely with different agents within a class.”