Back grey_arrow_rt.gif
HbA1c More Predictive than Glucose
  MedPage Today
March 04, 2010
Action Points
* Explain to patients that measuring glycated hemoglobin may be superior to fasting glucose levels as a means to estimate the risk of diabetes and cardiovascular disease.
Glycated hemoglobin (HbA1c) outperformed blood glucose as a predictor of cardiovascular disease (CVD) and all-cause mortality and had similar predictive accuracy for diabetes, data from a large cohort study showed.
As HbA1c values increased from <5% to ≥6.5%, the hazard ratio for diabetes rose from from <1 to >16 in nondiabetic adults, according to an article in the March 4 issue of the New England Journal of Medicine.
The corresponding hazard for coronary heart disease (CHD) more than doubled across the range of HbA1c values, and stroke risk increased in a similar manner, Elizabeth Selvin, PhD, of the Johns Hopkins School of Public Health, and co-authors reported.
HbA1c and all-cause mortality had a J-shaped association curve.
The associations remained significant after adjustment for baseline fasting glucose values. In contrast, fasting glucose did not predict cardiovascular risk or mortality after adjustment for baseline HbA1c values.
"Glycated hemoglobin values reflect the two-to-three-month average endogenous exposure to glucose, including postprandial spikes in the blood glucose level, and have low intraindividual variability, particularly in persons without diabetes," Selvin and colleagues wrote. "These characteristics may contribute to the superiority of glycated hemoglobin over fasting glucose for long-term macrovascular risk stratification."
"These data add to the evidence supporting the use of glycated hemoglobin as a diagnostic test for diabetes," they added.
Historically, HbA1c has been recommended only for monitoring glucose control in patients with diabetes. However, in its 2010 clinical practice recommendations, the American Diabetes Association advocated use of HbA1c to diagnose diabetes, primarily because of the parameter's established association with microvascular disease (Diabetes Care 2010; 33(Suppl 1): S13-S61).
Some evidence has suggested that elevated HbA1c is also a risk factor for macrovascular disease, the authors wrote.
Selvin and colleagues hypothesized that HbA1c would be superior to fasting glucose as a predictor of new-onset diabetes, CVD, and death. To test that theory, they analyzed data from the Atherosclerosis Risk in Communities (ARIC) trial, a prospective cohort study of 15,792 middle-age adults.
The analysis included 11,092 ARIC participants who provided blood samples at a follow-up visit between 1990 and 1992. Diagnosis of diabetes was based on self-reports and patient records. New-onset CVD was determined on the basis of patient and hospital records. Adjudicated follow-up data for CVD were available to Jan. 1, 2006.
Baseline HbA1c values of 5.0% to <5.5% were associated with a hazard ratio of 1.0 for diabetes and CVD and served as the reference.
The 15-year incidence of diagnosed diabetes in the cohort was 20%. The incidence increased from 6% to 79% across the HbA1c categories.
Values <5.0% were associated with hazard ratio of 0.52 (95% CI 0.40 to 0.69) for diabetes, increasing to a hazard of 16.47 (95% CI 14.22 to 19.08) for HbA1c values >6.5%.
For CHD, the lowest HbA1c values were associated with a hazard ratio of 0.96 (0.74 to 1.24), increasing to 1.95 (95% CI 1.53 to 2.48) for values >6.5%.
Hazard ratios for ischemic stroke increased from 1.09 for HbA1c values <5.0% to 3.16 for values >6.5%.
The hazard for death from any cause was 1.48 for ARIC participants with the lowest HbA1c values, declining to 1.00 for the reference, and then increasing to 1.65 for participants with the highest HbA1c values.
Comparison of glucose levels of <100 mg/dL with levels of >100 to <126 mg/dL yielded a statistically significant hazard ratio of 2.31 (95% CI 2.06 to 2.59) for diabetes, but not for CHD (HR 1.03, 95% CI 0.91 to 1.18), ischemic stroke (HR 0.97, 95% CI 0.76 to 1.23), or death from any cause (HR 1.07, 95% CI 0.96 to 1.21).
Undiagnosed diabetes (baseline glucose values >126 mg/dL) had significant, independent associations with CHD (HR 1.29, 95% CI 1.04 to 1.61), ischemic stroke (HR 1.89, 95% CI 1.33 to 2.69), and death from any cause (HR 1.31, 95% CI 1.07 to 1.61).
The authors also compared the predictive value of three categories of HbA1c (<6.0%, 6.0 to <6.5%, and ≥6.5%) with that of three categories of fasting glucose (<100 mg/dL, 100 to <126 mg/dL, and ≥126 mg/dL).
All three categories of HbA1c had significant associations with CHD, ischemic stroke, and death from any cause within each category of fasting glucose. In contrast, fasting glucose was not associated with any of the three outcomes among participants with baseline HbA1c values <6.0%.
The investigators noted that the study was limited by a single baseline determination of HbA1c, a small number of fasting blood glucose measurements during the follow-up period, and self-reports of diagnosis of diabetes during follow-up.
They also noted that unrecognized confounding could not be eliminated due to the observational design of the study.
  icon paper stack View Older Articles   Back to Top