During a joint symposium on Saturday, held as part of the 80th American Diabetes Association Scientific Sessions and hosted by JDRF President and CEO Aaron Kowalski, PhD, experts debated the merits and pitfalls of how to measure glycemic control and overall health among persons with diabetes. Which is better, they asked: the traditional measure of glycated hemoglobin or the newer measure, time-in-range?
Diabetes experts, patients, and advocates have debated the question for some time: is the better measure of glycemic control and overall health the traditional one, glycated hemoglobin (A1C)? Or should the field adopt a newer measure, time-in-range (TIR), based on data tracked with a continuous glucose monitor?
The quesiton made for an interesting discussion Saturday at a joint symposium held by the JDRF and the International Society for Pediatric and Adolescent Diabetes (ISPAD), hosted by JDRF President and CEO Aaron Kowalski, PhD. The symposium was part of the 80th American Diabetes Association Scientific Sessions, held in a virtual format due to coronavirus disease 2019 (COVID-19), which has hit people with diabetes especially hard.
William E. Winter, MD, of the University of Florida made the case for the use of A1C in pediatric diabetes, while Thomas Danne, MD, of Diabetes Center Auf der Bult in Hannover, Germany, made the case for TIR as the primary metric in pediatric care.
The A1C measure, taken with a blood test, evaluates an average of blood glucose levels as a percentage of red blood cells over the past 2 to 3 months. TIR is the amount of time a person spends with blood glucose levels in a healthy target range, usually 70 to 180 mg/dL (as patients’ glycemic control improves, the top end of the range may be lowered to 140 mg/dL). Patients say TIR more accurately reflects the swings of blood sugar throughout the day—which can affect how they feel and their work performance, as well as have long-term complications if such variability goes unchecked.
Although use of TIR has been gaining fans, A1C remains the standard, especially among those who see its value from a population health perspective. Whether A1C had as much value for pediatric patients was questionable, however.
Enter COVID-19, and a whole new question emerges: what if it’s not safe to get a blood test?
Danne said the pandemic has shown the value of continuous glucose monitoring (CGM) and TIR. “We had to change our whole way how we ran our diabetes clinics and changed to video consulting,” Danne said. Patients who had been reluctant to share their data on the cloud were suddenly compelled to do so. Families responded to the need to proactively manage a child’s blood glucose as never before.
“In many cases, it really allowed the whole family to discuss the glycemic profiles and how to change it by using time-in-range,” he said. In contrast with what was expected, the pediatric data from during the lockdown, including data from Italy, show TIR is improving.
“I think this COVID-19 crisis tells us one thing—time-in-range can be used for pediatric diabetes management and to help the family in goal setting. We have to, of course, give them clear goals, and I think we have the metrics today to do that,” he said.
Winter offered an overview of the history of how the A1C measure came about, to its use in the historic Diabetes Complications and Control Trial (DCCT), which found that intensively controlling A1C in patients with type 1 diabetes (T1D) to around 7% could keep microvascular complications such as retinopathy at bay, compared with traditional care that allowed A1C to drift up to 9%.
Using A1C as a yardstick in adults has offered several advantages, Winter said. “It predicts diabetes in adults,” he said. “When we’re talking about type 2 diabetes, it diagnoses diabetes in children and adults.”
Because A1C is done with a blood test, he said, it’s a “readily accessible marker that is inexpensive, and you can do it on a single blood draw any time of the day or night.”
Using A1C can predict a range of complications, from microvascular, to neuropathic, to macrovascular. However, the DCCT and other studies have shown that controlling A1C among adults does not necessarily reduce macrovascular disease. If so, is it a good way to predict these problems in children?
“One of the hypotheses put forward as to why these trials did not show reduced macrovascular disease is that possibly interventions did not begin early enough in life,” Winter said. “Because we know atherosclerosis is a chronic process, even in otherwise normal American kids. You can find fatty streaks in the aorta by age 3; you can find fatty streaks in the coronary arteries by age 10.”
He doesn’t see A1C, the “master biomarker” of diabetes, falling out of favor any time soon. “It’s useful as the universal standard for the assessment of long-term glycemic control. It's easily accepted accessible to the patient—it’s simple, nonfasting versus the complexity and cost of CGM.”
Nonetheless, Winter said the A1C measure has several well-known limitations:
In pediatric diabetes, especially T1D, the A1C measure falls short in assessing the 2 things that put children at immediate risk: hyperglycemia and hypoglycemia. Clearly, something else was needed to help children—and especially their parents—monitor blood glucose levels to ensure basic safety and to avoid long-term complications.
The rise of CGM, including newer devices that don’t require finger sticks and demand less and less patient management, has offered opportunities for TIR data to be available to broader groups of patients, including those with T2D. Coverage decisions here are still evolving. For the young patient with T1D, CGM is the standard of care, yet access to technology remains a challenge for some.
Danne, a former head of ISPAD, then discussed the value of the TIR measurement. He agreed to a point with Winter that cost and access can be problems with CGM. But then, Danne said, he wouldn’t have predicted 10 years ago that smart phones would be ubiquitous, even in the poorest corners of the globe, and insulin dosing software can often run off a patient’s phone without the need for a separate device.
“So, I'm pretty sure that if we, as a community, push for availability of continuous glucose monitoring, very soon the discussion about agency will quiet down considerably,” Danne said.
He discussed the SWEET initiative, a network of pediatric diabetes centers that began in Europe and is now worldwide. The project promoted best practices for pediatric diabetes technology, starting with insulin pumps and later continuous glucose monitors. Since 2008, the project has collected data from more than 60,000 patients, and the researchers involved have shown that giving patients more ambitious targets leads to better results.
While SWEET has used A1C as a benchmark, the importance of TIR has increased over the years, Danne said. CGM has made lowering the benchmark A1C from 7.5% to 7% possible. “This change in using CGM, it completely revolutionizes the way that we are treating the patients—or rather, I should say, patients and families are self-treating themselves.”
With CGM and TIR, he said, “They now have a parameter that allows them to see change in their glycemic control in more or less real-time fashion.”
If a patient adjusts an insulin dose or eats something outside a dietary plan, “time-in-range may improve or get worse. And it tells them whether they’re going in the right direction or not.”
Younger patients are more tech savvy, and today’s families are more willing to give their children with T1D access to CGM—in part because many models let parents monitor blood sugar remotely.
Why is TIR so important, Danne asked. He showed an example of metrics from patients who all had the same A1C but wildly different measures for TIR. Measures of improvement, thus, can be seen in how many more minutes a patient can spend in range over time. “If you’re looking at 24 hours, and somebody offers you 1 more hour of quality time per day, I guess you would say, ‘Yes,’ I do want to have that.”
If patients with a continuous glucose monitor can improve their TIR by 5% or more, Danne said, the hope would be that there would be significant clinical improvement. The use of CGM and the focus on TIR also allows for day-to-day adjustments in insulin, food intake, or other variables like exercise to keep patients working on glycemic control.
Discussant Daniel DeSalvo, an assistant professor of pediatrics at Baylor College of Medicine, said the use of CGM and TIR allows for personalized strategies in diabetes care that can lead to rapid improvement in glycemic control. However, he recommends a step-wise approach with patients new to CGM—focus first on avoiding hypoglycemia, then avoid the most dangerous levels of hyperglycemia, then gradually add additional alarms to tighten glycemic ranges and add insulin boluses to a regimen.
Insurance coverage for CGM in pediatric diabetes is improving, DeSalvo said. Today, “We now have over 70% of patients with private health insurance on CGM within 3 months of their diabetes diagnosis,” and Texas Medicaid recently added CGM coverage. “So, we hope to see a more equitable distribution of CGM across a broader diabetes aggregation in our clinic.” He added that the role of the diabetes care team is important in getting patients using CGM and sticking with it—which leads to better TIR.
These tools are becoming more convenient, with greater ability to interact with other devices such as an Apple Watch, and more customizable for young patients who are also athletes and want to participate in sports. “You can actually program it for the next day,” DeSalvo said.