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Variable HbA1c heightens risk for cardiometabolic disorders in type 2 diabetes
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Adults with type 2 diabetes may be at higher risk for major adverse cardiovascular events, coronary artery disease and other cardiometabolic disorders if they consistently experience large changes in HbA1c, according to findings published in Diabetes Care.
“Our study shows that higher HbA1c variability from the diagnosis of diabetes is independently associated with increased risks of all-cause mortality and major cardiovascular and microvascular complications of diabetes,” Ewan R. Pearson, MD, professor of diabetic medicine in the division of population health and genomics at the Ninewells Hospital and School of Medicine of the University of Dundee in Scotland, and colleagues wrote.
Pearson and colleagues assessed HbA1c variability, all-cause mortality and the prevalence of major adverse CV events, atherosclerotic CV death, CAD, stroke, heart failure, diabetic retinopathy, diabetic peripheral neuropathy, diabetic foot ulcer and chronic kidney disease among 21,352 adults with type 2 diabetes (mean age, 63.3 years; 45.4% women) who were residents of Tayside and Fife and included in the Scottish Care Information-Diabetes Collaboration. During a median of 6.8 years of follow-up, the researchers determined what percentage of a participant’s HbA1c readings featured a 0.5% or greater variation in HbA1c. This equated to what the researchers defined as a participant’s HbA1c variability score, or HVS.
“We used the HVS, rather than standard deviation or coefficient of variation, which we feel is much more clinically tractable,” the researchers wrote. “Although standard deviation and coefficient of variation reflect the dispersion trend of the HbA1c measures in an individual, they are no more than clinically meaningless statistical parameters.”
The researchers found that a greater than 60% HVS was reached by 12.5% of participants, and a 40% or less HVS was reached by 62% of participants. The reference group in this cohort was participants with 20% variability or less, and these participants made up 33.2% of the study population.
The risk for major adverse CV events was 2.38 times greater for those with at least 80% variability compared with the reference group (HR = 2.38; 95% CI, 1.61-3.53). In addition, compared with the reference group, the risk for all-cause mortality was 2.4 times greater (HR = 2.4; 95% CI, 1.72-3.33), the risk for atherosclerotic CV death was 2.4 times greater (HR = 2.4; 95% CI, 1.13-5.11), the risk for CAD was 2.63 times greater (HR = 2.63; 95% CI, 1.81-3.84), the risk for stroke was 2.04 times greater (HR = 2.04; 95% CI, 1.12-3.73), the risk for heart failure was 3.23 times greater (HR = 3.23; 95% CI, 1.76-5.93), the risk for diabetic retinopathy was 7.4 times greater (HR = 7.4; 95% CI, 3.84-14.27), the risk for diabetic peripheral neuropathy was 3.07 times greater (HR = 3.07; 95% CI, 2.23-4.22), the risk for diabetic foot ulcer was 5.24 times greater (HR = 5.24; 95% CI, 2.61-10.49) and the risk for CKD was 3.49 times greater (HR = 3.49; 95% CI, 2.47-4.95) among those with more than 80% HbA1c variability.
The researchers also found that risks for these conditions were also significantly greater for those with HbA1c variability of more than 60% but no more than 80% and for those with HbA1c variability of more than 40% but no more than 60% compared with reference, except for stroke, which did not reach significance in those with variability of more than 40% but no more than 60%. In addition, the researchers noted that when adding adjustments for time-weighted averaged HbA1c, age, sex and baseline treatment, “the results were similar for most outcomes other than retinopathy, where the association of HVS was diminished when adjusting for time-weighted averaged HbA1c.”
“Our results indicate that frequent fluctuations of HbA1c of patients with diabetes may be an independent risk factor for poor prognosis, and more stable HbA1c control may benefit the patients in clinical practice,” the researchers wrote. – by Phil Neuffer
Disclosures: The authors report no relevant financial disclosures.
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