Glucose Variability and Cardiovascular Risk

Controlling blood glucose in patients with diabetes mellitus reduces the risk of cardiovascular (CV) complications.1 While the UK Prospective Diabetes Study and others have related fasting plasma glucose level (FPG) and hemoglobin A,_c (HbA,_c) to CV outcomes, a recent interim analysis of the major NIH-funded study of patients with type 2 diabetes, the ACCORD trial, now indicates that there might be a limit to the benefits and degree of HbA,_c reduction. Although specifics of the trial are yet to be published, the data analysis and safety board terminated the tight control arm of this treatment trial because of a small but significant increase in mortality. As a result, the target HbA,c for many patients with CVD will, in all likelihood, remain above the nondiabetic range.

Glucose variability, another measure of glycemic control, also relates to CV outcomes. This metric quantitates the change in glucose concentration from before a meal to that obtained afterwards and can be used to assess risk and monitor treatment effectiveness. When control is targeted to minimize glucose fluctuations, even if the HbA,_c is above normal, there are cardiovascular advantages.

Consider an example of two patients with type 2 diabetes and similar HbA,c results: one patient with the continuous glucose monitoring (CGMS) tracing A, the other with tracing B (Figure 1). The tracings record three days each. Then ask, "Do these two patients have the same cardiovascular risk?" Current evidence suggests the answer is no! The patient with tracing A, with greater variability, carries a two- to three-fold increased risk of primary and secondary macrovascular disease.2•³ The purpose of this review is to examine the relationship between glucose variability and cardiovascular disease.