Connecting the Dots: Validation of Time in Range Metrics With Microvascular Outcomes

The landmark Diabetes Control and Complications Trial (DCCT) identified the relationship between intensive diabetes management for those with type 1 diabetes (T1D) and a delay in the onset or progression of microvascular complications, shifting the paradigm of clinical care for this chronic medical condition (1). Importantly, the data from that trial continue to have a lasting legacy as they can now be analyzed to inform present-day questions. An example of this comes from the article by Beck et al. in this issue of Diabetes Care (2) that concisely states the primary implication of the article in its title, “Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials.” In recent years, and with increasing use of continuous glucose monitoring (CGM), the ability to classify sensor glucose levels into various ranges has been feasible. Yet, some have questioned the validity of using these measures as a surrogate outcome measure in ongoing and future clinical trials. Indeed, some have called for a “modern-day” DCCT assessing whether CGM and a greater time in range (TIR) would result in fewer microvascular end points compared with self-monitoring of blood glucose (with intermittent masked CGM). Unfortunately, the duration of time, funds required, and ethical concerns given clinical equipoise regarding the benefits of the technology would make completion of a rigorous randomized controlled trial a near-impossible feat. Recognizing the wealth of data that the DCCT affords, Beck et al. (2) found a creative solution to assess the hypothesis of whether TIR could serve as an outcome measure for future trials. Specifically, they capitalized on the glucose values captured seven times daily every 3 months during the course of the 6+ years of the DCCT. This allowed them to calculate the percent TIR of glucose values between 70 and 180 mg/dL and show a robust …