Spotlight on glycemic variability

Two studies published in July looked at the causes and consequences of variation in glycemic control between clinic visits.

The first study, published by Diabetic Medicine on July 29, included 10,130 Scottish patients with type 2 diabetes. The patients' glycemic variability was calculated based on a minimum of four HbA1c readings obtained over four years. Patients were also stratified by their mean HbA1c (above or below 7%). The study found that intensity of treatment was the factor most strongly associated with high variability among HbA1c readings. Patients on triple oral therapy or insulin were much more likely to be in the top tertile of variability (sixfold more likely if their mean HbA1c was <7%, threefold more likely if their mean HbA1c was ≥7%, both compared to those on no treatment or monotherapy). Other factors independently associated with glycemic variability were male sex, younger age, low HDL cholesterol level, and high body mass index.

In other studies, these factors have also been associated with cardiovascular disease risk, as has glycemic variability. The authors said that “it is uncertain whether the adverse cardiovascular outcomes reported to be associated with increased HbA1c variability can be attributed to the high HbA1c variability per se, or more simply reflects the high cardiovascular risk factors seen in people with type 2 diabetes who exhibit high HbA1c variability.” The study also could not determine whether the association between intensive treatment and HbA1c variability was causal. The authors noted that glycemic variability may have a number of causes, including lifestyle factors (exercise, stress, treatment adherence) and biological mechanisms.

The other study, published by Diabetes Care on July 13, included 16,706 Taiwanese patients with type 2 diabetes, age 60 years or older. None of them had a diagnosis of Alzheimer's disease (AD) at baseline. During a median follow-up of 8.88 years, 831 cases of AD were identified. Researchers compared the visit-to-visit variability of the patients' fasting plasma glucose level and HbA1c, using data from at least two visits within a year. The study found that patients in the highest variability tertile had significantly higher risk of developing AD (hazard ratios, 1.25 [95% 1.06 to 1.52] for variable fasting glucose and 1.32 [95% CI, 1.11 to 1.58] for HbA1c).

This study is the first to find such an independent association, according to the study authors. “Our findings indicate the existence of a shared pathophysiological link between glycemic variability and AD,” they wrote. The study also showed that the stability of glycemic control can be evaluated in practice and that there is a weak correlation between variability in fasting plasma glucose and HbA1c, the authors said. Fasting plasma glucose might be a more sensitive marker than HbA1c for glucose variability due to changes in eating, they said. The authors suggested that cognitive functions be screened routinely in patients with type 2 diabetes, especially if they have notable glycemic variability. The authors concluded by calling for further research to confirm whether glycemic variability is a valuable therapeutic target for patients with type 2 diabetes at risk for AD.