Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials

By R. Beck, R. Bergenstal, Tonya D. Riddlesworth, C. Kollman, Zhaomian Li, Adam S. Brown, Kelly L Close. Diabetes Care, 2018

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OBJECTIVE This study evaluated the association of time in range (TIR) of 70–180 mg/dL (3.9–10 mmol/L) with the development or progression of retinopathy and development of microalbuminuria using the Diabetes Control and Complications Trial (DCCT) data set in order to validate the use of TIR as an outcome measure for clinical trials. RESEARCH DESIGN AND METHODS In the DCCT, blood glucose concentrations were measured at a central laboratory from seven fingerstick samples (seven-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. Retinopathy progression was assessed every 6 months and urinary microalbuminuria development every 12 months. Proportional hazards models were used to assess the association of TIR and other glycemic metrics, computed from the seven-point fingerstick data, with the rate of development of microvascular complications. RESULTS Mean TIR of seven-point profiles for the 1,440 participants was 41 ± 16%. The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51–78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25–56), for each 10 percentage points lower TIR (P < 0.001 for each). Results were similar for mean glucose and hyperglycemia metrics. CONCLUSIONS Based on these results, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials. Although hemoglobin A1c remains a valuable outcome metric in clinical trials, TIR and other glycemic metrics—especially when measured with continuous glucose monitoring—add value as outcome measures in many studies.

Subfields: Endocrinology, Diabetes and Metabolism, Nephrology

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In Endocrinology, Diabetes and Metabolism

Citations in the corpus

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021, methodology): “Although the evidence of HbA1c reduction remains the most robust measure associated with chronic diabetes complications and is the only measure that is prospectively validated, more recent studies have begun to examine the relationship between time that glucose is within the target range and long-te”
Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019, methodology): “0 mmol/L]) with diabetes complications (49,50) as well as a relationship between TIR and A1C (26,27).”