Does glucose variability influence the relationship between mean plasma glucose and HbA _1c levels in type 1 and type 2 diabetic patients?

OBJECTIVE - The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA _1c and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-HbA _1c relationship. RESEARCH DESIGN AND METHODS - Analyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-HbA _1c relationship. RESULTS - GV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-HbA _1c relationship in type 1 diabetic patients so that high GV led to a higher HbA _1c level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the HbA _1c level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency. CONCLUSIONS - In only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with HbA _1c. This effect is more pronounced at higher HbA _1c levels. However, the impact of GV on the HbA _1c level in type 1 diabetes is modest, particularly when HbA _1c is close to the treatment target of 7%.