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Original Investigation
February 7, 2017

Association of Sickle Cell Trait With Hemoglobin A1c in African Americans

Author Affiliations
  • 1Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island
  • 2Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive, and Kidney Diseases and the National Institute of Minority Health and Health Disparities, National Institutes of Health, Bethesda, Maryland
  • 3Department of Medicine, University of Mississippi Medical Center, Jackson
  • 4Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
  • 5Division of Hematology, Oncology & SCT, Ann & Robert H. Lurie Children’s Hospital, Chicago, Illinois
  • 6Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson
  • 7Department of Laboratory Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland
  • 8Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis
  • 9Department of Epidemiology, School of Public Health, University of Alabama at Birmingham
  • 10Department of Biostatistics, Brown University School of Public Health, Providence, Rhode Island
  • 11Department of Epidemiology, University of Washington School of Public Health, Seattle
  • 12Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
  • 13Center for Innovation in Long-Term Services and Support, Providence Veterans Affairs Medical Center, Providence, Rhode Island
  • 14Division of Cardiology, Providence Veterans Affairs Medical Center, Providence, Rhode Island
  • 15Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island
JAMA. 2017;317(5):507-515. doi:10.1001/jama.2016.21035
Key Points

Question  Does hemoglobin A1c reflect past glucose concentrations in a similar manner in African Americans with sickle cell trait as it does in those without sickle cell trait?

Findings  In this retrospective cohort study of 4620 African Americans, for any given fasting or 2-hour glucose concentration, individuals with sickle cell trait had significantly lower hemoglobin A1c values, 5.72% vs 6.01%, than those without sickle cell trait.

Meaning  Among African Americans with sickle cell trait, hemoglobin A1c concentration may systematically underestimate past glycemia and should be further evaluated.


Importance  Hemoglobin A1c (HbA1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it.

Objective  To evaluate the association between SCT and HbA1c for given levels of fasting or 2-hour glucose levels among African Americans.

Design, Setting, and Participants  Retrospective cohort study using data collected from 7938 participants in 2 community-based cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). From the CARDIA study, 2637 patients contributed a maximum of 2 visits (2005-2011); from the JHS, 5301 participants contributed a maximum of 3 visits (2000-2013). All visits were scheduled at approximately 5-year intervals. Participants without SCT data, those without any concurrent HbA1c and glucose measurements, and those with hemoglobin variants HbSS, HbCC, or HbAC were excluded. Analysis of the primary outcome was conducted using generalized estimating equations (GEE) to examine the association of SCT with HbA1c levels, controlling for fasting or 2-hour glucose measures.

Exposures  Presence of SCT.

Main Outcomes and Measures  Hemoglobin A1c stratified by the presence or absence of SCT was the primary outcome measure.

Results  The analytic sample included 4620 participants (mean age, 52.3 [SD, 11.8] years; 2835 women [61.3%]; 367 [7.9%] with SCT) with 9062 concurrent measures of fasting glucose and HbA1c levels. In unadjusted GEE analyses, for a given fasting glucose, HbA1c values were statistically significantly lower in those with (5.72%) vs those without (6.01%) SCT (mean HbA1c difference, −0.29%; 95% CI, −0.35% to −0.23%). 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 (mean, 5.35%) vs those without SCT (mean, 5.65%) for a mean HbA1c difference of −0.30% (95% CI, −0.39% to −0.21%). The HbA1c difference by SCT was greater at higher fasting (P = .02 for interaction) and 2-hour (P = .03) glucose concentrations. The prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA1c values (29.2% vs 48.6% for prediabetes and 3.8% vs 7.3% for diabetes in 572 observations from participants with SCT and 6877 observations from participants without SCT; P<.001 for both comparisons).

Conclusions and Relevance  Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA1c at any given concentration of fasting or 2-hour glucose compared with participants without SCT. These findings suggest that HbA1c may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.