Association of Estimated Time-in-Range Capillary Glucose Levels Versus HbA(1c) With Progression of Microvascular Complications in the Diabetes Control and Complications Trial

OBJECTIVE Estimated time in range (eTIR) obtained from DCCT glucose profiles (pre- and postprandial and bedtime) was recently reported to be associated with microvascular outcomes and was recommended as a clinical trial outcome, but without consideration of HbA(1c). RESEARCH DESIGN AND METHODS The associations of eTIR with diabetic retinopathy and microalbuminuria were assessed without and with adjustment for HbA(1c) and baseline covariates. RESULTS Adjusted for HbA(1c) and covariates, eTIR was marginally significantly associated with retinopathy in the full cohort (hazard ratio [HR] 1.12 per 10% lower eTIR [95% CI 1.0, 1.26], P = 0.042). Conversely, HbA(1c) was significantly associated with both outcomes (HR >= 1.19 per 0.5% higher HbA(1c), P <= 0.0002) in five of six adjusted analyses. CONCLUSIONS The association of eTIR with complications is largely explained by its correlation with HbA(1c). HbA(1c), not eTIR or continuous glucose monitoring TIR, remains the preferred outcome in clinical studies of type 1 diabetes complications.