A 15-year, multicenter study has changed the course of care for youth with type 2 diabetes, enhancing treatments for this growing population and illustrating the scope of the work conducted on the CU Anschutz Medical Campus. Called Treatment Options for Type 2 Diabetes in Adolescents & Youth (TODAY), the massive clinical trial included 699 participants and was led nationally by Phil Zeitler, MD, professor, pediatrics-endocrinology, University of Colorado School of Medicine.
The study, which wrapped up at the end of 2022, has already changed the way doctors treat adolescents and young people with type 2 diabetes. The scholarship it has produced is vast. So far, 74 papers have been published with more currently in preparation. “It is the only source of hard data on the treatment of kids as well as the disease course. It is by far the most detailed set of data on kids with type 2 diabetes,” Zeitler said.
In terms of day-to-day management, monitoring, screening and recommendations from the American Diabetes Association and International Society for Pediatric and Adolescent Diabetes (ISPAD), all of it is based on findings from TODAY, Zeitler said.
The most recent paper to be published is first-authored by Janine Higgins, PhD, co-investigator of TODAY and director of operations for the Colorado Clinical and Translational Sciences Institute (CCTSI). The findings, published in Diabetes Care, show that glucose variability, rather than the standard clinical measure of HbA1c concentration, can more quickly predict loss of glycemic control and development of long-term complications at 10 years. These findings are another step to help manage Type 2 diabetes in youth more quickly and effectively.
The information in Higgins’ publication is just one component in an extensive catalogue of information doctors can now use to inform the care they provide to their young patients with type 2 diabetes, which unfortunately continues to increase each year. (The Centers for Disease Control and Prevention reports that rates of type 2 diabetes are skyrocketing in Black and Hispanic youth.)
The primary takeaway from TODAY overall is that type 2 diabetes in adolescents and youth progresses more rapidly than the same disease in adults.
As Zeitler is fond of saying, “This is not your grandma’s diabetes.” Though type 2 diabetes in adolescents has a lot of similarities to the disease in adults, it has unique features that demand distinctly different treatment.
“We need to pay close attention to type 2 diabetes when it is developed as a child. It is not the same course as in an adult. We can’t treat it the same way,” Higgins said.
“The disease progresses more rapidly in the sense that initial therapy does not necessarily last as long. So, there is a higher failure rate with therapy,” Zeitler said. “It becomes more difficult to control.”
Moreover, treatments that may work in adults often are ineffective in adolescents and youth.
In 2021, the New England Journal of Medicine published findings from the Treatment Options for Type 2 Diabetes in Adolescents and Youth follow-up study (TODAY2). In this paper, authors show that youth-onset type 2 diabetes leads to serious complications by early adulthood.
The good news is there are now drug treatment options for the disease that did not even exist when TODAY started in 2004. Here in Colorado and across the country, physicians are currently studying the effectiveness of these treatments in youth with several clinical trials.
Higgins explains that once a study closes, the NIH normally does a follow-on study. But she said with TODAY, so many poor outcomes were discovered so early in life, the NIH is doing something very unusual. “We are doing a prequel,” Higgins said. “We are going back in time to see what precipitates this disease in kids.”
The study is in the design phase now and will be co-led by Kristen Nadeau, MD, and Megan Kelsey, MD, at Children’s Hospital Colorado and in the CCTSI’s Clinical Translational Research Center.
Zeitler said, “We know there is a very close relationship of onset [of the disease] and puberty. So, the next study will put together a large cohort of kids who are pre-pubertal to try to understand who gets the disease and what are the predictors, so we may understand how to intervene to prevent it.”