Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial

There is uncertainty about the importance of glycemic variability in cardiovascular complications in patients with type 2 diabetes. Using the Veterans Affairs Diabetes Trial (VADT), we investigated the association between variation in fasting glucose and glycated hemoglobin (HbA_1c) over time and the incidence of cardiovascular disease (CVD) and assessed whether this is influenced by intensive or standard glycemic control.

During the VADT, fasting glucose and HbA_1c were measured every 3 months for up to 84 months in 1,791 individuals. Variability measures included coefficient of variation (CV) and average real variability (ARV) for fasting glucose and HbA_1c. Overall mean glucose and HbA_1c measures as well as their maximum and the most recent measurement were also examined.

Variability measures (CV and ARV) of fasting glucose were significantly associated with CVD even after adjusting for other risk factors, including mean fasting glucose. When considering separately groups receiving intensive and standard glycemic control, this relationship was evident in the intensive treatment group but not in the standard group. Additional adjustment for severe hypoglycemic episodes did not alter the relationship between fasting glucose variability and CVD. Interestingly, no HbA_1c measures were associated with CVD after adjusting for multiple baseline risk factors.

Our analysis indicates that in the VADT, variability of fasting glucose plays a role in the development of CVD complications beyond the influence of standard fasting glucose measures. The adverse consequences of fasting glucose variability on CVD appear greatest in those receiving intensive glucose control.