SAN FRANCISCO – according to presenters at the annual scientific sessions of the American Diabetes Association.
“More research is urgently needed to better understand the reasons for this more serious trajectory,” said Philip Zeitler, MD, PhD, professor of pediatric endocrinology at the University of Colorado and medical director of Children’s Hospital Colorado Clinical & Translational Research Center, Aurora. The hope is to identify children at risk and prevent disease, but at this point “we don’t know the answer,” he added.
In the meantime, “we are getting more aggressive with bariatric surgery at our center because nothing else is working. It would be nice to move away from that, but these kids are dying,” he said.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria ().
A study he presented at the meeting – an 8-year follow-up the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, dubbed TODAY 2 – illustrates why. Published in 2011, the original trial found benefit for metformin alone or in combination with rosiglitazone.
Overall, 517 participants still are being followed. They’re managed in community practices now, and are in their early 20s, on average.
Less than 10 years down the road from TODAY, “these kids have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring” at a time that “should be the most productive period of their lives,” Dr. Zeitler said.
“The disease is much more aggressive in youth than in adults,” said Steven E. Kahn, MB, ChB, an endocrinology professor and director of the Diabetes Research Center at the University of Washington, Seattle, who presented a second study at the meeting – the Restoring Insulin Secretion Study (RISE) – that brought the point home.
Among other things,compared 12 months of metformin or insulin glargine followed by metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance. Treatments were stopped after 12 months, and the participants were reevaluated at 15 months.
Treatment improved insulin sensitivity and beta-cell response in the adults, and they reverted to baseline at 15 months. There were no improvements in children, however, and they were worse off at 15 months than they had been at baseline. Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications ().
“This was the first ever true comparison of outcomes in youths versus adults,” with the same study design and lab measurements in both arms. The difference in outcomes was “very scary,” Dr. Kahn said.
Perhaps there’s something worse about developing diabetes during puberty, which is already an insulin-resistant state, or maybe something else is going on. Whatever the case, “there’s an urgent need” to better understand the differences between kids and adults, and for better treatments in kids, Dr. Kahn said.
As for weight loss, “it’s not just that these kids can’t discipline themselves. You need to understand that type 2 diabetes in kids occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s complex,” Dr. Zeitler said.
The cardiovascular event rate in TODAY 2 – heart attacks, heart failure, and stroke, among others – is about the same as in older adults with type 1 diabetes. Renal function is declining, and there have been two cases each so far of chronic kidney disease and end stage renal failure.
Women in the cohort, about two-thirds of the study population, have had high rates of maternal and offspring complications.
Serious eye problems are common, and “we’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
The National Institutes of Health funded the study. The presenters reported no relevant disclosures or conflicts of interest.