Association of Sickle Cell Trait With Hemoglobin A1c in African Americans.
Hemoglobin A1c (HbA1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it.



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



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.



Presence of SCT.



Hemoglobin A1c stratified by the presence or absence of SCT was the primary outcome measure.



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).



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.
Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island.
Mary E
ME
Lacy
Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island.
Gregory A
GA
Wellenius
Diabetes, 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.
Anne E
AE
Sumner
Department of Medicine, University of Mississippi Medical Center, Jackson.
Adolfo
A
Correa
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Mercedes R
MR
Carnethon
Division of Hematology, Oncology & SCT, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois.
Robert I
RI
Liem
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
James G
JG
Wilson
Department of Laboratory Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
David B
DB
Sacks
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis.
David R
DR
Jacobs
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham.
April P
AP
Carson
Department of Biostatistics, Brown University School of Public Health, Providence, Rhode Island.
Xi
X
Luo
Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island.
Annie
A
Gjelsvik
Department of Epidemiology, University of Washington School of Public Health, Seattle.
Alexander P
AP
Reiner
Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Rakhi P
RP
Naik
Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island15Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island.
Simin
S
Liu
Department of Medicine, University of Mississippi Medical Center, Jackson.
Solomon K
SK
Musani
Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island.
Charles B
CB
Eaton
Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island13Center for Innovation in Long-Term Services and Support, Providence Veterans Affairs Medical Center, Providence, Rhode Island14Division of Cardiology, Providence Veterans Affairs Medical Center, Providence, Rhode Island15Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island.
Wen-Chih
WC
Wu
D001741:Black or African American; D001786:Blood Glucose / Q000032:analysis* / Q000378:metabolism; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology; D005215:Fasting / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011236:Prediabetic State / Q000175:diagnosis / Q000453:epidemiology; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012805:Sickle Cell Trait / Q000097:blood*; D013997:Time Factors
D001786:Blood Glucose; D006442:Glycated Hemoglobin