The vicious cycle of adolescent diabetes
It's a familiar story in the U.S., particularly among minority populations. For Hispanic youth like Mona, the rate of diabetes is about 17% of the total population. For Native Americans, the rate approaches half. And as studies follow these kids over time, the outlook grows increasingly grim.
"Complication rates are high," says pediatric endocrinologist Philip Zeitler, MD, PhD, national primary investigator for the now-famous TODAY study, the first large-scale research on treatment options for diabetic youth, published in the New England Journal of Medicine in 2012. Now 15 years out from diagnosis, many of the study's more than 600 young adults are developing eye disease, kidney disease, high blood pressure.
"They're only 25 or 30," he remarks. "They're not 60."
Mona was headed down that path. At age 19, she couldn't spend five minutes walking without getting tired. She'd sweat just shopping for groceries. For a girl who prided herself on being active, it was embarrassing. She got depressed. And the depression led to more weight.
Limited effectiveness of exercise for adolescent diabetes
Liz had been there. She'd gotten bariatric surgery, as had Mona's three aunts. It helped a lot. But when it came to Mona, her family was split on the issue. She seemed too young. Her grandmother didn't think she should do it. Neither did her brother.
"He personally thought I could do it on my own," Mona recalls. "He's like, 'Go to the gym. Work out.'"
But as intuitive as that solution sounds, it doesn't have a great track record. TODAY's lifestyle intervention failed to yield statistically significant results.
"Even with intensive medicinal therapy, diabetes in teens tends to get worse over time," says Associate Surgeon-in-Chief Thomas Inge, MD, national primary investigator of Teen-LABS, the first long-term study of bariatric surgery in adolescents, published in JAMA Pediatrics in 2014. "That's what TODAY showed."
A dim outlook for teens with prediabetes
Before TODAY, there was no consistent course of treatment for kids with type 2 diabetes. Pediatric providers sporadically treated with metformin, although nobody knew what that would look like long-term, and rosiglitazone had just hit the market. TODAY tested both. Neither performed as expected based on the adult literature. Metformin had a failure rate of 13% in adults. In kids it was more like 50%.
"And failure meant we couldn't manage them with oral medicines. They had to go on insulin, and then you have shots, checking blood sugar multiple times a day. It's more expensive. There's more risk," says pediatric endocrinologist Kristen Nadeau, MD, MS. "So the thought was, well, maybe TODAY intervened too late. Maybe you can't even wait until diabetes sets in. So we recruited kids with less than 6 months of diabetes, and another half with prediabetes."
That work became the RISE study, for which Dr. Nadeau has served as national primary investigator. She and her multicenter peers knew teens were more resistant to insulin because of the hormonal environment of puberty. RISE's latest results from August 2018 show that youth have lower insulin sensitivity compared with adults.
If you could give those overtaxed beta cells a rest early, they hypothesized, maybe you could improve their function. In August 2018, RISE also published their findings from one group on 12 months of metformin and another on 3 months of insulin, followed by 9 of metformin.
"These kids' maximal beta cell response actually got worse on treatment," says Dr. Nadeau. "Some of the kids, their blood sugar got so high they couldn't even come in for the last measurement."
For some kids, beta cell response will get better when they grow out of puberty and their insulin resistance ends. But for about half of the kids in TODAY, that beta cell function never came back.
Read all of the latest research findings from the RISE consortium on PubMed.
Bariatric surgery for teens: a new paradigm
As an adult gastroenterological surgeon in the late 1990s, Dr. Inge performed bariatric surgeries on adults long before almost anyone would perform one on a teen. Dr. Inge's first, during his first year of pediatric practice, was an extreme case: an adolescent weighing 400 lbs. with obstructive sleep apnea so severe his otolaryngologist and pulmonologist were considering a tracheostomy. But because of the thickness of the patient's neck, they feared that, too, could threaten his life.