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Visit-to-Visit Variability of Hemoglobin A1c in People Without Diabetes and Risk of Major Adverse Cardiovascular Events and All-Cause Mortality

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OBJECTIVE We aimed to study whether visit-to-visit variability of glycated hemoglobin A 1c (HbA 1c ) is associated with incident major adverse cardiovascular events (MACE), all-cause mortality, and type 2 diabetes in people without diabetes. RESEARCH DESIGN AND METHODS We included primary care patients with no history of diabetes or cardiovascular disease and with three annual HbA 1c measurements within normal range (<6.5% [48 mmol/mol]). For each individual, we measured the HbA 1c variability as the SD of the residuals obtained from a linear regression on the three HbA 1c measurements. From the linear regression, we also obtained the estimated index HbA 1c (intercept) and the trend over time (slope). Follow-up began at the date of the third measurement. Associations between HbA 1c variability and outcome were analyzed using Cox regression, adjusted for traditional risk factors, intercept, and trend and reported as hazard ratio per SD increase in variability (HR SD ). RESULTS In total, 6,756 individuals were included. During a median follow-up time of 6.3 years, 996 developed MACE, 856 died, and 1,267 developed type 2 diabetes. We found a significant association between increasing HbA 1c variability and incident MACE (HR SD 1.09 [95% CI 1.03–1.15]) and all-cause mortality (HR SD 1.13 [95% CI 1.07–1.20]), whereas there were no associations with type 2 diabetes (HR SD 1.00 [95% CI 0.95–1.05]). We calculated 5-year absolute risks of MACE and all-cause mortality and found clinically relevant differences across several age, sex, comorbidity, and HbA 1c variability–defined subgroups. CONCLUSIONS In a primary care population free of diabetes and cardiovascular disease, high HbA 1c variability was associated with increased risks of MACE and all-cause mortality.

Original languageEnglish
JournalDiabetes Care
Volume42
Issue number1
Pages (from-to)134-141
Number of pages8
ISSN1935-5548
DOIs
Publication statusPublished - Jan 2019

    Research areas

  • Aged, Blood Glucose/metabolism, Cardiovascular Diseases/blood, Comorbidity, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glycated Hemoglobin A/analysis, Humans, Incidence, Male, Middle Aged, Mortality, Proportional Hazards Models, Risk Factors, Sensitivity and Specificity

ID: 55527434