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%.