Objective
The objective of this study is to validate continuous glucose monitoring based time in range (TIR) between 70 and 180 mg/dL as a primary measure of diabetes control and risk factor for diabetic retinopathy in patients with type 1 diabetes across a range of different age groups sexes.
Background Rationale
The Diabetes Control and Complications Trial established hemoglobin A1c as the main measure of diabetes control and complications risk. A1c has been the measure of diabetes control discussed by patients and providers for over 30 years. Despite its widespread use, A1c is an imperfect measure as it is highly variable between different tests, is prone to ethnic bias, and does not reflect hypoglycemia exposure. Continuous glucose monitoring (CGM) use has grown significantly over the past decade and provides real-time measurement of both hypoglycemia and hyperglycemia exposure. Glucose time in range (TIR) between 70 and 180 mg/dL has been demonstrated to predict diabetes complications based on fingerstick data. Indirect evidence has shown that CGM TIR also predicts rates of complications in various studies. In order for TIR to be fully accepted by insurance companies, regulatory agencies such as the Food and Drug Administration, and more patients and clinicians direct evidence needs to show the relationship between CGM TIR and diabetes outcomes. This study will use data from the Barbara Davis Center to directly demonstrate the relationship between CGM TIR and diabetic retinopathy.
Description of Project
Hemoglobin A1c has served as the measure of diabetes control for over 30 years. It is well established that across large populations of people, higher A1c values are associated with higher rates of diabetes complications. Despite its central place within diabetes care, A1c has many flaws as a visit-to-visit measure for individuals: A1c can vary by as much as 0.5% from test-to-test, A1c provides no reflection of hypoglycemia exposure, and there are noted racial differences in A1c values. With the recent growth in continuous glucose monitoring (CGM), Time In Range (TIR) between 70 and 180 mg/dL has been proposed as a new measure which can address these deficits. Reanalysis of TIR with fingerstick data from the Diabetes Control and Complications Trial has shown that this measure predicts complications in the same way as A1c. Thus while TIR has been validated with fingerstick data, we still need to validate TIR with real-world CGM data. This project will utilize long-term electronic medical record data from the Barbara Davis Center, one of the world’s largest type 1 diabetes centers, to examine the relationships between CGM TIR and diabetic retinopathy. We will also work with biostatisticians to develop a new TIR metric which is better adjusted for duration and severity of hyper- and hypoglycemia. The results of this project will provide the data that patients, providers, and payers will need to adopt TIR as the main measure of diabetes control.
Anticipated Outcome
This project will evaluate association between CGM TIR as a predictor of diabetic retinopathy. We anticipate that CGM time in range will strongly predict the risk of diabetic retinopathy in men and women with type 1 diabetes. We will also explore association between glycemic variability and a new TIR adjusted for duration of hyperglycemia with diabetic retinopathy. We anticipate that short duration excursions out of target range will not be meaningful while a metric, which better accounts for long duration excursions, will better account for the risk of diabetic retinopathy.
Relevance to T1D
Hemoglobin A1c has long been the main measure of diabetes control discussed by patients and providers during clinical care and examined by researchers in trials. All have been frustrated with the variability of this tests, and the limits of what it tells us about diabetes control. Continuous Glucose Monitoring (CGM) Time in Range (TIR) between 70 and 180 mg/dL has begun to emerge as a better measure of diabetes control and complications risk. This project will provide strong direct evidence to association of CGM TIR with diabetic retinopathy allowing for more widespread adoption of this measure by payers, regulatory agencies, providers, and patients.