Hemoglobin A1c Variability Metrics Predict Coronary Artery Calcium and Cardiovascular Events in Type 1 Diabetes: The
William B Horton1, Janet K Snell-Bergeon2
1Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
Insights
In type 1 diabetes, various hemoglobin A1c (HbA1c) metrics predict cardiovascular disease risk and events. These HbA1c measures are linked to coronary artery calcium and predict future cardiovascular events in T1D patients.
Area of Science:
- Endocrinology
- Cardiology
- Diabetes Research
Background:
- Type 1 diabetes (T1D) management aims to reduce micro- and macrovascular complications.
- Despite glucose control, cardiovascular disease (CVD) risk in T1D remains higher than in the general population.
- Factors beyond average glucose levels (HbA1c) likely influence CVD outcomes in T1D.
Purpose of the Study:
- To investigate if different hemoglobin A1c (HbA1c) metrics predict cardiovascular disease (CVD) risk factors and events in individuals with T1D.
- To assess the relationship between various HbA1c measures and anatomic CVD risk indicators.
Main Methods:
- Utilized the CACTI Study cohort (NCT00005754) for analysis.
- Employed linear regression to examine associations between HbA1c metrics and CVD risk factors.
- Applied Cox regression to model the predictive relationship of HbA1c metrics with incident CVD events.
Main Results:
- Baseline HbA1c, mean HbA1c, and HbA1c standard deviation (SD) positively correlated with coronary artery calcium volume.
- Mean HbA1c was also associated with increased pericardial adipose tissue volume.
- Baseline, mean, time-varying HbA1c, and HbA1c SD independently predicted incident CVD events over a median follow-up of 14.3 years.
Conclusions:
- Various HbA1c metrics are associated with subclinical CVD indicators like coronary artery calcium in T1D.
- Different HbA1c measures, including baseline, mean, and time-varying levels, independently predict future CVD events in T1D.
- These findings highlight the importance of considering HbA1c variability and specific metrics beyond average levels for CVD risk assessment in type 1 diabetes.
Context:
Interventions that decrease mean glucose have reduced rates of micro- and macrovascular complications in type 1 diabetes (T1D). However, the difference in cardiovascular risk between people with T1D and the general population endures, suggesting that factors beyond hemoglobin A1C (HbA1c) normalization drive cardiovascular outcomes.
Objective:
To determine whether various HbA1c metrics predict anatomic cardiovascular disease (CVD) risk factors and/or CVD events in people with T1D.
Methods:
We used linear regression to analyze the relationship of several HbA1c metrics to anatomic CVD risk factors and then used Cox regression to model their relationship to incident CVD events in the CACTI Study (ClinicalTrials.gov Identifier: NCT00005754).
Results:
In linear regression models adjusted for age, sex, and T1D duration, baseline Hba1c (b = 0.3998, P = 0.0236), mean HbA1c (b = 0.5385, P = 0.0109), and HbA1c SD (b = 1.1521, P = 0.0068) were each positively associated with square root transformed coronary artery calcium volume. Conversely, only mean HbA1c (b = 1.659, P = 0.0048) positively associated with pericardial adipose tissue volume. In survival models adjusted for age, sex, and T1D duration, baseline HbA1c [hazard ratio (HR): 1.471, 95% CI: 1.257-1.721], mean HbA1c (HR: 1.850, 95% CI: 1.511-2.264), time-varying HbA1c (HR: 1.500, 95% CI: 1.236-1.821), and HbA1c SD (HR: 1.665, 95% CI: 1.022-2.711) each independently predicted CVD events over 14.3 ± 5.2 person-years of follow-up.
Conclusions/Interpretation:
We found that various HbA1c metrics positively correlated with CAC volume and independently predicted incident CVD events in the CACTI T1D cohort. These associations with CVD events persisted for baseline HbA1c, mean HbA1c, and time-varying HbA1c even after adjustment for numerous CVD risk factors.
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