Can Metformin Help Kids at Puberty?
Megan Kelsey, MD
Pediatrician, University of Colorado–Denver
Pediatric Insulin Resistance
|ADA Research Funding
Junior Faculty Grant
Not so long ago, type 2 diabetes was known as "adult-onset diabetes," because the disease was almost unknown in children. But type 2 is on the rise in children, particularly adolescents. "All kids who get type 2 diabetes are at least overweight, and usually obese," says pediatrician Megan Kelsey.
There's something else almost all of them have in common: They've all entered puberty. Kelsey, a doctor at the University of Colorado–Denver, is trying to figure out why—and how doctors might be able to prevent type 2 diabetes in teens.
She's zeroed in on insulin—or, more precisely, insulin resistance—as a possible cause. With normal metabolism, every time people eat, insulin is released to help the body's cells fuel themselves with glucose circulating in the bloodstream. At specific stages in life, though, insulin fulfills a different role: It signals the body to grow. During puberty and pregnancy, insulin that usually helps to process the glucose from the foods we eat is instead working to trigger the changes that go along with those phases of life.
The result amounts to a temporary bout of insulin resistance. Ordinarily, the body responds by making more insulin, enough to take care of daily metabolic needs and keep the body growing to boot. "In lean, healthy people, you would never notice," Kelsey says.
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But for the 17 percent of American children who are obese, making enough insulin to take care of daily needs is already a struggle. Ramping up insulin output even further, to keep up with the demands of puberty, may be too much. For obese children, the combined stress can push the pancreas (the organ that makes insulin) to the breaking point.
That, Kelsey says, is probably why most type 2 diabetes cases in children develop during puberty. With the help of a grant from the American Diabetes Association, she's researching the impact of obesity to see if overweight and obese kids are more insulin resistant and therefore more likely to overwork the pancreas as they go through a growth spurt. "That's what we think is going on. You just don't see type 2 diabetes before puberty," she says.
In a study she's named Health Influences of Puberty, or HIP, Kelsey is comparing kids not at risk for type 2 diabetes—lean, healthy kids—with those who are obese as they enter puberty. The key measurement is an IV glucose tolerance test, which tracks the body's response to glucose over the course of a few hours. "The faster glucose goes down after insulin goes up, the more sensitive they are," Kelsey says. When glucose levels stay up or decrease very slowly in response to the body's release of insulin, insulin resistance
Kelsey hopes to recruit about 100 kids in all, divided into three groups. The first is a "control" group of lean kids; another is made up of obese kids. A third group of obese kids would test out the possibility that taking metformin (a drug that increases insulin sensitivity and helps the body absorb glucose) during puberty might help prevent diabetes.
Although metformin is one of the world's most widely prescribed anti-diabetes drugs, there's very little research on how it works in children. "A lot of people are using metformin for insulin resistance, but we don't have any research evidence for using it in pediatrics," Kelsey says. "Kids aren't small adults—their disease processes work differently."
The idea of putting kids on metformin during puberty is a reluctant acknowledgment of a tough truth: More and more children are entering puberty overweight or obese, and the rates of type 2 diabetes in teens are rising accordingly. "If we could get kids to lose weight, that would be great," Kelsey says. "Lifestyle changes seem to be the best way to [prevent] diabetes in adults, but it's very difficult to get adolescents in particular to adhere to lifestyle changes."
Kelsey hopes the HIP study—which may run for three more years, following participants all the way through puberty—comes up with ways to help prevent type 2 diabetes in teens. Perhaps, she says, taking metformin during puberty might give the pancreas some backup when insulin resistance is at its worst. "The point would be to only treat kids temporarily, so they're not committed to taking medication long-term," she says.