Association of sickle cell trait with hemoglobin A1c in African Americans

Mary E. Lacy, Gregory A. Wellenius, Anne E. Sumner, Adolfo Correa, Mercedes R. Carnethon, Robert I. Liem, James G. Wilson, David B. Sacks, David R. Jacobs, April P. Carson, Xi Luo, Annie Gjelsvik, Alexander P. Reiner, Rakhi P. Naik, Simin Liu, Solomon K. Musani, Charles B. Eaton, Wen Chih Wu

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


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.

Original languageEnglish
Pages (from-to)507-515
Number of pages9
JournalJAMA - Journal of the American Medical Association
Issue number5
StatePublished - Feb 7 2017

Bibliographical note

Funding Information:
CARDIA is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN26820090004 from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005). The JHS is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the NHLBI and the National Institute on Minority Health and Health Disparities. Dr Lacy was supported by F31DK105791 (DrsWu andWellenius are cosponsors of this grant). DrWu was supported by the Center of Innovation in Long-Term Services and Support, Providence VA Medical Center. Dr Carson was supported by K01DK095928. Dr Sumner is supported by the intramural program of NIDDK and NIMHD. Dr Sacks is supported by the Intramural Research Program of the NIH. Dr Naik was supported by NHLBI grant K08HL125100. Joint calling of exome sequence data in JHS was supported by R01HL107816 to S. Kathiresan, who was the principal investigator of the ancillary study that obtained the SCT data on JHS participants.

ASJC Scopus subject areas

  • General Medicine


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