Estimated Glucose Disposal Rate and Risk of Vascular Events and Death in Type 2 Diabetes in the ADVANCE Study

ABSTRACT Aims To determine the association of insulin resistance, assessed using the estimated glucose disposal rate (eGDR), and the risk of adverse clinical outcomes, and determine any effect modification on the efficacy of glucose‐ and blood pressure (BP)‐lowering treatments. Materials and Methods Briefly, 11 140 participants with type 2 diabetes (T2D) were recruited from 20 countries for the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. eGDR was derived from waist circumference, hypertension status and glycated haemoglobin, calculated in 11 081 participants. Multivariable Cox models were used to estimate hazard ratios (HRs) of the association of eGDR with clinical events. Results Over a median of 5 years of follow‐up, 2117 participants (19.1%) experienced a major macrovascular or microvascular event. Compared with individuals in the lowest quarter of eGDR, those in the highest quarter had significantly lower risks of a composite major macrovascular and microvascular event (HR 0.72, 95% CI 0.62–0.84). Similar associations were seen for major macrovascular events (HR 0.68, 95% CI 0.55–0.85), major microvascular events (HR 0.78, 95% CI 0.63–0.96), all‐cause mortality (HR 0.69, 95% CI 0.55–0.86), and cardiovascular mortality (HR 0.62, 95% CI 0.45–0.85). No significant effect modification was observed across eGDR quarters for the efficacy or safety of intensive glucose control (vs. standard control) or BP–lowering treatment (vs. placebo). Conclusion These findings highlight the value of eGDR as a prognostic marker for T2D. Intensive glucose‐ and BP‐lowering treatments remain beneficial regardless of insulin resistance status. Trial Registration: ClinicalTrials.gov identifier: NCT00145925