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Sickle Cell Trait & HbA1c in African Americans

JAMA; 2017 Feb 7; Lacy, Wellenius, et al

African Americans with sickle cell trait (SCT) had lower levels of hemoglobin A1c at any given concentration of fasting or 2-hour glucose compared with those without SCT, a recent study found. This retrospective cohort study included 4,260 African American participants (mean age, 52.3 years, 61.3% women, 7.9% with SCT); with 9,062 concurrent measures of fasting glucose and HbA1c levels. Researchers found:

  • Participants with SCT had significantly lower HbA1c values than those without sickle cell trait (5.72% vs 6.01%).
  • Findings were similar in models adjusted for key risk factors and in analyses using 2001 concurrent measures of 2-hour glucose and HbA1c concentration for those with SCT vs those without SCT.
  • Prevalence of prediabetes and diabetes was statistically significantly lower among those with SCT when defined using HbA1c values.

Citation:

Lacy ME, Wellenius GA, Sumner AE, et al. Association of sickle cell trait with hemoglobin A1c in African Americans. JAMA. 2017;317(5):507-515. doi:10.1001/jama.2016.21035.

Commentary:

HgA1c is formed by glucose binding over time to the hemoglobin molecule. A potential misinterpretation of A1c is not understanding that A1c values can be affected by a number of things in addition to glucose level. Anything that decreases the red blood cell lifespan or increases the number of newly formed RBCs (consequently decreasing the time that the hemoglobin in circulation is exposed to the ambient blood sugar level), will decrease the A1c for any given level of blood glucose compared to what it would have been with a normal red blood cell lifespan. Examples of this decreased red blood cell time in circulation include hemolytic anemia, destruction of RBCs from artificial heart valves, and patients with chronic kidney disease who receive erythropoietin.1 The current study shows that A1c is about 0.3% lower in patients with SCT, which occurs in approximately 10% of the black population.2 For black patients in whom the 0.3% difference in A1c may affect clinical decision making, it is may be helpful to check for SCT. —Neil Skolnik, MD

  1. Alarcon-Casas Wright L, Hirsh I. The challenge of the use of glycemic biomarkers in diabetes: Reflecting on hemoglobin A1c, 1,5-anhydroglucitol, and the glycated proteins fructosamine and glycated albumin. Diabetes Spectrum. 2012;25(3):141-148.
  2. Bleyer AJ, Aloi JA. Sickle cell trait and interpretation of hemoglobin A1c levels. JAMA. 2017;317(5):481-482. doi:10.1001/jama.2016.20994.