There is uncertainty about the importance of visit-to-visit glycemic variability in cardiovascular disease (CVD) complications in type 2 diabetes (T2D) patients. Using the Veteran Affairs Diabetes Trial (VADT), we investigated this relationship, and assessed whether it is influenced by intensive or standard glucose control. During the VADT, fasting glucose and HbA1c were measured every 3 months for up to 84 months in 1791 individuals. Visit-to-visit variability measures included coefficient of variation (CV) and average real variability (ARV). By Cox proportional hazard models, variability measures of fasting glucose showed significant association with CVD even after adjusting for other risk factors, including mean fasting glucose. This relationship was evident in the intensive treatment group but not in the standard group (Figure 1). Additional adjustment for severe hypoglycemic episodes, did not alter the effect of glucose variability on CVD. Interestingly, HbA1c variability was not 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 the mean glucose measures. The adverse consequences of glucose variability on CVD appear greatest in those receiving intensive glucose control.

Figure 1

Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for the primary composite CVD outcome adjusted for ethnicity, baseline HbA1c, baseline HDL and LDL cholesterol, baseline total cholesterol and triglycerides, history of hypertension, diabetes duration, prior CVD event, and the cumulative mean of glucose. Vertical bars are the 95% confidence interval (95% CI) associated with HR estimates. “***” indicates estimated HR in the related variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1).

Figure 1

Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for the primary composite CVD outcome adjusted for ethnicity, baseline HbA1c, baseline HDL and LDL cholesterol, baseline total cholesterol and triglycerides, history of hypertension, diabetes duration, prior CVD event, and the cumulative mean of glucose. Vertical bars are the 95% confidence interval (95% CI) associated with HR estimates. “***” indicates estimated HR in the related variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1).

Disclosure

J. Zhou: None. D. Schwenke: None. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company.

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