Wide Swings in Blood Glucose Linked to More CVD in Diabetes

Mitchel L. Zoler, PhD

February 11, 2021

Patients with type 2 diabetes and the highest level of variability in their A1c levels over 2 years had significantly more first cardiovascular disease (CVD) events than similar patients with less A1c variability, in a retrospective analysis of more than 29,000 US patients.

The findings by Yun Shen, MD, and colleagues, were published in Diabetes Obesity and Metabolism.

"We recommend that patients [with type 2 diabetes] and their doctors implement therapies that can reduce wide swings in blood sugar levels and the associated [hypoglycemic] episodes," said Gang Hu, MD, PhD, senior author and director of the Chronic Disease Epidemiology Lab at Pennington Biomedical Research Centers in Baton Rouge, Louisiana, in a statement.

A "Supplemental Blood Glucose Target"

"Our findings suggest that measuring the swings in blood hemoglobin A1c levels over a specific time — 6 months to a year, for example — could serve as a supplemental blood glucose target," added Hu.

The reasons for the link are not clear. A possible explanation is that higher levels of A1c variability reflect an increased rate of severe episodes of hypoglycemia, the authors suggest.

Large glycemic variability has also been associated with poor adherence to treatment, poor self-efficacy in diabetes management, complications with comorbid conditions, and poor quality of life with a lack of support.

For the analysis, Shen, also of Pennington Biomedical Research Centers, and colleagues used data collected in the Louisiana Experiment Assessing Diabetes Outcomes (LEAD) study from more than 100,000 patients diagnosed with type 2 diabetes and managed in either of two health systems in Louisiana.

Excluding patients with a history of CVD and fewer than four A1c measurements during the first 2 years following diabetes diagnosis left 29,260 patients for the analysis. During the 2 years between diabetes diagnosis and study entry, these patients averaged nine A1c measurements apiece.

The study's primary outcome was incident CVD events, including coronary heart disease and stroke. CVD events occurred in 3746 patients during an average 4-year follow-up after establishing each patient's level of A1c variability.

The researchers acknowledge that "there are no standardized definitions for A1c variability," but they applied three different statistical methods for calculating variability, and all three produced consistent and statistically significant results.

For example, their basic standard deviation analysis showed, after adjustment for multiple potential confounders, that patients in the quartile with the greatest level of A1c variability had a 59% higher rate of CVD events compared with patients in the quartile with the lowest rate of A1c variability.

The rate of CVD events increased steadily with rising variability across the four quartiles, and overall, every 1 unit increase in A1c standard deviation was linked with a significant 18% rise in CVD events after adjusting for confounders.

"Our findings suggest that A1c variability over a specific time period could be considered a supplementary glycemic target, and therapies that can reduce large A1c variability as well as associated severe hypoglycemic events are recommended for patients with type 2 diabetes," the authors reiterate.

Diabetes Obes Metab. 2021;23:125-135. Full text

The study received no commercial funding. The authors have reported no relevant financial relationships.

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