Unlocking puzzles in pediatric diabetes

Dr. Steven Kahn, study chair for the Restoring Insulin Secretion (RISE) Consortium, talks with RISE participant Faamafi Faamafi Jr. about medication options for adults who are at high risk for Type 2 diabetes. Kahn is a professor of medicine at the University of Washington School of Medicine and an endocrinologist at VA Puget Sound Health Care. The site was one of eight RISE locations across the country looking at Type 2 diabetes treatments in children and adults. (Christopher Pacheco / VA Puget Sound Health Care System)

As more kids are diagnosed with Type 2 diabetes – historically an adult disease – a new study has found that the adult medications being used to treat them don’t work as well to slow the disease’s progression.

The study, lead by a Seattle professor, looked at children ages 10-19 in two groups: Kids with prediabetic blood glucose levels and those with recent-onset Type 2 diabetes.

Researchers found that in youth treated with long-acting insulin followed by the drug metformin, and in a separate group receiving metformin alone, neither of these approaches preserved the body’s ability to make insulin. The medications also didn’t slow progression of Type 2 diabetes.

“These findings tell us that the treatments that work on adults and that we currently use for Type 2 diabetes in youth are not as effective as we would like,” said Dr. Steven Kahn, a professor at the University of Washington School of Medicine and an endocrinologist at VA Puget Sound Health Care.

“We need to develop new approaches to treat adolescents with the disease.”

Kahn chairs the national study and leads the Seattle site. Researchers say that it’s clear from this study and others that Type 2 diabetes in youth is more aggressive than in adults.

For those with diabetes, the body doesn’t make enough or properly use insulin, a hormone that turns food into energy. It has two main forms: Type 1 and Type 2.

Type 1, formerly called juvenile diabetes, is an autoimmune disease that triggers the body to attack the beta cells in the pancreas so the body produces little or no insulin.

Previously called adult-onset diabetes, Type 2 is the most common form and occurs when blood glucose is too high and the body doesn’t make enough insulin or doesn’t use insulin well to counteract it. Too much glucose then stays in the blood, and not enough reaches cells. It’s often associated with obesity.

The longer a person has Type 2 diabetes, the greater the likelihood of developing heart, kidney, eye and nerve diseases. Because it’s long been an adult condition, pediatric diabetes experts have had to rely on best practices for adult treatments, researchers say.

This study raises questions about why medications that slow progression in adults don’t have the same effect on youth, said Lisa Randall, an Inland Northwest Health Services certified diabetes educator.

Randall, who read the study’s findings, noted that part of it looked at kids who were prediabetic and whether medication can delay onset of the disease, as it can in prediabetic adults.

“Basically what they found is it doesn’t work as well,” she said. “What we’ve known about kids and Type 2 diabetes for a while is that they progress very rapidly to Type 2 diabetes, whereas in an adult it may be two to 20 years. I am curious why it happens so rapidly in kids.

“What is happening is these kids are very insulin resistant – they’re making a ton of insulin, but it’s not working.”

Giving insulin and oral medication to adults often works effectively by taking the burden off the beta cells to produce all that insulin, she said.

Youth at four study sites were randomly assigned to one of two treatment groups. The first received three months of glargine insulin followed by nine months of metformin. The second group received only metformin for 12 months. All were monitored for three months after treatment ended.

“If we get an adult who has prediabetes or newly diagnosed Type 2, and we give them insulin and or metformin, they respond by having improved outcomes for years,” Randall said. The children on both insulin and metformin and those on menformin alone did not see, she added, “an impact on improving beta cell function. That’s the problem. Improving beta cell function or at least halting the destruction of beta cells is how we prevent the progression from prediabetes to diabetes.”

However, she said along with medications for children and adults, “really the most powerful treatment we have is exercise.”

The trials are among the first to compare youth with Type 2 diabetes to their adult counterparts to see if early, aggressive treatment would improve outcomes.

Kahn said the pediatric study found that beta cell function – key to the body’s ability to make and release insulin – declined in both groups and worsened after treatment ended. The two medications reviewed are the only FDA-approved ones for children.

“These studies provide critical new information that helps us better understand why Type 2 diabetes seems to progress more rapidly in young people,” Kahn said. “This is important news given the growing epidemic of this disease in youth, who were previously spared of Type 2 diabetes.

“What is getting more and more scary is that the number kids who have this disease is increasing.”

About 193,000 Americans younger than 20 are estimated to be diagnosed with diabetes. The prevalence of Type 2 diabetes in youth from 2000 to 2009 jumped more than 30 percent to a rate of 2.3 patients per 5,000 kids, a 2014 national study said.

It’s typically higher among minority racial and ethnic groups such as Native Americans and Alaskan natives, Kahn said. He cites a need for a national push to defeat obesity.

Kahn said parents and physicians need to ensure that children with Type 2 diabetes continue using one or both medications, “or they’re likely to progress faster.”

“The first message is because your kid has Type 2 diabetes, this is not hopeless or lost,” Kahn said. “The much bigger issue is the societal issue. Obesity is a major driver of the problem.”

A push toward more nutritional foods – while moving away from dishes loaded with calories – has to start in the home and reach to a national stage. And, “we’ve got to increase physical activity.”

Further research is needed, Kahn added, including impacts from hormones during puberty. Other medications are available for adults but not yet tested for children. He said the Restoring Insulin Secretion, or RISE, studies have yielded enough blood samples for more advanced comparisons as more research funding is secured.

One hypothesis is yet to be studied, he said. The cells in the pancreas that make hormones responsible for glucose control are made in a mini-organ called the islet, which has beta cells making insulin and also alpha cells making glucagon. Insulin will lower glucose, and glucagon will raise glucose.

“In an individual with diabetes when glucose falls too low, they will secrete glucagon to try to raise the glucose up again,” Kahn said. “One possibility is this relationship that’s normally very tight and regulated between the amount of insulin and glucagon being secreted – that we know a lot about in adults – may be disturbed.

“Maybe what kids are doing are secreting more insulin and also secreting more glucagon than adults, which is driving them through the physiological mechanism to get them to a point to progress more rapidly. If that concept was true, one might target the alpha cell in these kids in a different way.”

The pediatric medication study results recently were published in Diabetes Care with two other manuscripts comparing youth with adults participating in trials under the RISEstudy.