Glycemic Variability May Predict Incident Cardiovascular Disease, Mortality

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The researchers’ findings contribute to a growing body of evidence regarding the prognostic value of glycemic variability.

Greater visit-to-visit variability of fasting blood glucose is associated with an increased mortality risk but not with incident cardiovascular events, according to the prospective cohort analysis results published in Diabetes Care.

The researchers conducted an observational analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ( identifier: NCT00000542) to assess the association of visit-to-visit variability and fasting blood glucose with incident cardiovascular events and all-cause mortality in individuals with and without diabetes.

The study included 4982 participants who had completed the baseline, 2-year, and 4-year visits in the ALLHAT trial and did not experience a CV event or die before the 4-year mark. Researchers excluded participants from the doxazosin treatment arm of ALLHAT, as well as patients with incomplete data on the covariates. Further, participants who did not have cardiovascular disease (CVD) during the first 4 years of the study were followed for incident CVD such as coronary heart diseases, stroke, and heart failure, and all-cause mortality.

Since there are no internationally agreed upon measures of glycemic variability in general and visit-to-visit variability in particular, alternative visit-to-visit variability of fasting blood glucose metrics measured by the researchers included the coefficient of variation, the variability independent of the mean, and the average successive variability.

The primary outcome was the incidence of CVD events and the secondary outcome was all-cause mortality. Over a median follow-up of 5 years, there were 305 CVD events (189 coronary heart disease, 45 stroke, and 81 heart failure) and 154 deaths. The adjusted hazard ratio (HR) comparing participants in the highest vs lowest quartile of standard deviation of fasting blood glucose (≥26.4 mg/dL vs <5.5 mg/dL) was 1.43 (95% CI, 0.93-2.19) for CVD and 2.22 (95% CI, 1.22-4.04) for all-cause mortality. The HR for variability independent of the mean was 1.17 (95% CI, 0.84-1.62) for CVD and 1.89 (95% CI, 1.21-2.93) for all-cause mortality. In individuals without diabetes, the highest quartile of standard deviation of fasting blood glucose (HR 2.67; 95% CI, 0.14-6.25) or variability independent of the mean (HR 2.50; 95% CI, 1.40-4.46) conferred a higher risk for death.

Furthermore, researchers highlighted that the association of glycemic variability and mortality was significant and greater in magnitude in people without diabetes compared with people with diabetes.

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Ultimately, the prognostic significance of the relationship between clinical outcomes and glycemic variability represents a lacunae in studies pertaining to glycemic levels.  However, the strength of this study lies in the inclusion of a large and multiethnic sample of participants.

Researchers noted, “Glycemic variability has emerged as a measure that could more accurately capture the pathological processes presiding over the occurrence of complications. It is therefore a potentially important predictor of hyperglycemia-related complications, which would be highly relevant for prognosis.”

Please refer to reference for a complete list of authors’ disclosures.

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Echouffo-Tcheugui JB, Zhao S, Brock G, Matsouaka RA, Kline D, Joseph JJ. Visit-to-visit glycemic variability and risks of cardiovascular events and all-cause mortality: The ALLHAT study [published online January 18, 2019]. Diabetes Care. doi:10.2337/dc18-1430