Association of Sickle Cell Trait With Hemoglobin A<sub>1c</sub> in African Americans
Authors: 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
Journal: JAMA (2017)

<h3>Importance</h3> Hemoglobin A<sub>1c</sub>(HbA<sub>1c</sub>) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it. <h3>Objective</h3> To evaluate the association between SCT and HbA<sub>1c</sub>for given levels of fasting or 2-hour glucose levels among African Americans. <h3>Design, Setting, and Participants</h3> 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 HbA<sub>1c</sub>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 HbA<sub>1c</sub>levels, controlling for fasting or 2-hour glucose measures. <h3>Exposures</h3> Presence of SCT. <h3>Main Outcomes and Measures</h3> Hemoglobin A<sub>1c</sub>stratified by the presence or absence of SCT was the primary outcome measure. <h3>Results</h3> 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 HbA<sub>1c</sub>levels. In unadjusted GEE analyses, for a given fasting glucose, HbA<sub>1c</sub>values were statistically significantly lower in those with (5.72%) vs those without (6.01%) SCT (mean HbA<sub>1c</sub>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 HbA<sub>1c</sub>concentration for those with SCT (mean, 5.35%) vs those without SCT (mean, 5.65%) for a mean HbA<sub>1c</sub>difference of −0.30% (95% CI, −0.39% to −0.21%). The HbA<sub>1c</sub>difference by SCT was greater at higher fasting (<i>P</i> = .02 for interaction) and 2-hour (<i>P</i> = .03) glucose concentrations. The prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA<sub>1c</sub>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;<i>P</i>&lt;.001 for both comparisons). <h3>Conclusions and Relevance</h3> Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA<sub>1c</sub>at any given concentration of fasting or 2-hour glucose compared with participants without SCT. These findings suggest that HbA<sub>1c</sub>may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.