Disclosures: The authors report no relevant financial disclosures.
July 29, 2021
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TODAY: Youth-onset type 2 diabetes precedes high burden of early adulthood complications

Disclosures: The authors report no relevant financial disclosures.
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Long-term follow-up of a cohort of children and adolescents diagnosed with type 2 diabetes showed most developed complications, including microvascular disease, in early adulthood that progressed steadily over time.

New analyses from the TODAY study, a multicenter, randomized trial of youths aged 10 to 17 years with recent-onset type 2 diabetes that began in 2004, also showed that complications were more common among participants from underrepresented groups and among those with hyperglycemia, hypertension and dyslipidemia. The findings were published in The New England Journal of Medicine.

Zeitler is a professor of pediatrics-endocrinology at University of Colorado Anschutz Medical Campus and medical director of the Children’s Hospital Colorado Clinical and Translational Research Center.

“Though it is difficult to directly compare rates of development of complications with that seen in adult-onset type 2 [diabetes], these results support the argument that this is occurring at least as rapidly as in adults — meaning, at a disease duration of 12 years or so, there is a high prevalence of complications similar to adult-onset,” Philip S. Zeitler, MD, PhD, professor of pediatrics-endocrinology at University of Colorado Anschutz Medical Campus and medical director of the Children’s Hospital Colorado Clinical and Translational Research Center, told Healio. “However, these individuals are only in their late 20s and experiencing life-changing and potentially life-limiting events, at a time when they should be at their peak health, productivity and life course. This has important implications for individuals, health care providers, health care systems, and policymakers.”

For the original TODAY study (2004-2011), researchers and assessed time to loss of glycemic control for children and adolescents with youth-onset type 2 diabetes assigned one of three treatments: metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention. Researchers then transitioned the participants to metformin with or without insulin and enrolled them in an observational follow-up study (2011-2020) conducted in two phases. Researchers assessed participants for diabetic kidney disease, hypertension, dyslipidemia and nerve disease annually; assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated.

At the end of the second phase of the follow-up study, the mean age of the 500 participants was 26 years; mean time since diabetes diagnosis was 13.3 years. Cumulative incidence of hypertension was 67.5%, incidence of dyslipidemia was 51.6%, incidence of diabetic kidney disease was 54.8%, and incidence of nerve disease was 32.4%.

The prevalence of retinal disease, including more advanced stages, was 13.7% when assessed in 2010-2011 and rose to 51% when assessed in 2017-2018. At least one complication occurred for 60.1% of participants and at least two complications occurred for 28.4%. Risk factors for the development of complications included non-white race, hyperglycemia, hypertension and dyslipidemia. No adverse events were recorded during follow-up.

Zeitler said there is a tendency among providers to pursue less treatment for youths because of age and hesitancy to expose them to medications; however, these data show these youths are at risk for development of serious life-threatening health problems.

“Therefore, although we did not specifically test the benefits of earlier, more aggressive intervention to control glucose and treat developing complications, these data support the need for more aggressive management, studies aimed at looking at these interventions more carefully, and updating of guidelines to consider these findings,” Zeitler said.

With these new data, study of the TODAY cohort is now complete, Zeitler said.

“NIH is now starting the process of putting together a new young cohort to address some of the questions raised by TODAY,” Zeitler said.