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Youth-onset Type 2 Diabetes Leads to Serious Complications As Soon As Young Adulthood, Major Study Finds


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UH Rainbow’s Rose Gubitosi-Klug, MD, PhD, was Vice Chair of Pivotal NEJM Study

Innovations in Pediatrics | Fall 2021

Rose Gubitosi-Klug, MD, PhDRose Gubitosi-Klug, MD, PhD

People who develop type 2 diabetes as children or teens are at high risk of developing complications from the disease as soon as their 20s and have a greater chance of developing multiple complications within just 15 years of their diagnosis – a phenomenon that is distinct to this young age group. That’s the conclusion of the TODAY2 study, recently published in The New England Journal of Medicine.

Rose Gubitosi-Klug, MD, PhD, Division Chief of Pediatric Endocrinology at UH Rainbow Babies & Children’s Hospital, was Vice Chair of the new NEJM study. She says she hopes the results will increase the urgency among healthcare providers and parents to aggressively treat overweight and obese children at risk for type 2 diabetes, given that study results show complications from the disease in children develop at an accelerated pace compared with adults.

“There’s always been this perception that these are kids, they have a long lifetime ahead of them, and weight issues take time to develop through habits and behaviors,” she says. “However, we now know that you can’t wait six months and see whether they are able to lose weight, because these complications will develop. The kids start to have the high blood sugars. And then the clock is ticking on these complications.”

TODAY2, begun in 2011, involved 500 original participants from the TODAY study, which began in 2004. TODAY, which included UH Rainbow as one of its original 15 sites, was the first major comparative effectiveness trial for the treatment of Type 2 diabetes in youth. At the time of enrollment, participants were between the ages of 10-17, had been diagnosed with type 2 diabetes for fewer than two years, and were overweight or obese. The average age of participants after the TODAY2 follow-up was 26 years.

Researchers monitored participants in TODAY2 annually for signs of diabetes complications, including heart disease, kidney disease, diabetic foot complications, and to report other health events. Diabetic eye disease was assessed once during the study, at the seven-year study visit. 

Results show that within 15 years of a type 2 diabetes diagnosis, 60% of participants had at least one diabetes-related complication, and nearly a third of participants had two or more complications. Overall, researchers saw a steady decline in blood glucose control over 15 years. In addition,

  • 67% of participants had high blood pressure
  • nearly 52% had dyslipidemia
  • nearly 55% had kidney disease
  • 32% had evidence of nerve disease
  • 51% had eye disease

According to Dr. Gubitosi-Klug, these findings reinforce the emerging consensus that type 2 diabetes in youth has a distinct and disruptive pathophysiology.

”Studies tell us that the effects on the pancreas and the beta cells that produce insulin are more dramatic in these children,” she says. “Their beta cells just don’t survive very long. They go from over-secreting the insulin to no longer being able to secrete the insulin – beta cell failure. As a result, these patients are much, much harder to manage. Our medications don’t seem to last. For an adult, it might be five years, 10 years until they need additional medications. These kids, within one or two years, they are failing the treatment. Something is triggering all of this at a very young age.”

One hypothesis, she says, is that the hormonal changes associated with puberty may play some role in the rapid development of complications in younger type 2 diabetes patients.

“If you are at risk for type 2 diabetes, and then you go into puberty and have excessive weight – all these factors seem to combine and your beta cells just can’t keep up. In a new NIH study, now just accepting applications, we want to recruit a group of overweight and obese children before puberty and follow them and their beta cell function. We want to see if we can find earlier markers to pick these kids up. There are a lot of children who are overweight or obese, but not every one of them is going to go on to have youth-onset type 2 diabetes. There have to be some other clinical indications that we can pick up on.”

In the meantime, Dr. Gubitosi-Klug’s advice to pediatricians and parents is to be vigilant and intervene early.

“Follow that BMI,” she says. “Work as diligently and hard with the families and community resources to change that weight trajectory for these children. If you cannot, do not wait to test their metabolic status. The treatment is continued lifestyle education, but they likely need to be started on oral medications. We believe that the sooner the better in trying to keep these beta cells alive.”

The stakes couldn’t be higher.

“This is a major public health issue for our country and for the world,” Dr. Gubitosi-Klug says. “When individuals are in their early 20s with all these complications, it will really limit their ability to work and contribute to their communities and families. It’s very staggering to think of the long-term effects.”

For more information, contact the Division of Pediatric Endocrinology at 216-844-3661.

Contributing Expert:
Rose Gubitosi-Klug, MD, PhD
Division Chief, Pediatric Endocrinology
William T. Dahms Chair in Pediatric Endocrinology
UH Rainbow Babies & Children’s Hospital
Professor of Pediatrics
Case Western Reserve University School of Medicine