Glycaemic variation is a predictor of all-cause mortality in the Veteran Affairs Diabetes Trial

Abstract

Diabetes is associated with substantially increased mortality. Classic risk factors explain a portion of the excess of mortality in type 2 diabetes. The aim of this study was to examine whether visit-to-visit variation in fasting glucose and haemoglobin A1c values in the Veteran Affairs Diabetes Trial were associated with all-cause mortality in patients with type 2 diabetes in addition to other comorbidity conditions, hypoglycaemic events and adverse lifestyle behaviours. The Veteran Affairs Diabetes Trial was a randomized trial that enrolled 1791 military veterans who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. During the Veteran Affairs Diabetes Trial, fasting glucose and haemoglobin A1c were measured quarterly for up to 84 months. Variability measures included coefficient of variation and average real variability. We found that variability measures (coefficient of variation and average real variability) of fasting glucose were predictors of all-cause mortality, even after adjusting for comorbidity index, mean fasting glucose and adverse lifestyle behaviour during the study. Accounting for severe hypoglycaemia did not weaken this association. Our analysis indicates that in the Veteran Affairs Diabetes Trial, longitudinal variation in fasting glucose was associated with all-cause mortality, even when accounting for standard measures of glucose control as well as comorbidity and lifestyle factors.

Keywords: Mortality; glycaemic control; hypoglycaemia; long-term glycaemic variability; type 2 diabetes.

Figure 1.

Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for mortality adjusted for age. Vertical bars shown are the 95% confidence interval (95% CI) associated with HR estimates. ***Estimated HR in the indicated variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1). Trend test results are presented as the text annotation in the figures. CV: coefficient of variation; ARV: average real variability.