Studying Metformin as Heart Protector in Teens
Kristen Nadeau, MD, MS
Endocrinologist, University of Colorado School of Medicine
ADA Research Funding
Career Development Grant
Heart health is something most people start worrying about in middle age. But new research suggests that for people with type 1 diabetes, cardiovascular disease—weak heart muscles, stiff or clogged arteries, and other factors that increase the risk of heart attack and stroke—may actually be a concern much earlier in life.
Kristen Nadeau, MD, MS, a researcher at the University of Colorado School of Medicine, says symptoms of heart disease show up as early as puberty. “There’s mild thickening of the heart arteries already in teenagers,” Nadeau says. “It’s a gradual process, not something that starts when you’re 50.”
Nadeau’s research, conducted with the help of a grant from the American Diabetes Association, is probing the reasons why. She thinks insulin resistance—when the body fails to respond properly to the insulin hormone—may contribute to cardiovascular disease in people with type 1, even if they are getting enough insulin to control their blood glucose. “It used to be thought that type 1 was just a matter of keeping blood sugar within range,” Nadeau says. “The thinking now is, in addition to the pancreas not making insulin, the body is more resistant.”
Researchers have already shown that in people with type 2 diabetes, insulin resistance contributes to an increased risk of heart disease. The same cause and effect may be at work in people with type 1 diabetes, who experience heart disease and other cardiovascular illnesses at nearly triple the rate of people without diabetes.
Blood glucose control, then, may not be enough to ward off associated health problems. People with type 1 may have their first encounter with insulin resistance as early as puberty. “During puberty, kids are more insulin resistant, or insulin doesn’t work as well,” Nadeau says. “Some of the extra insulin may go to growth spurts.”
Because puberty has such a high degree of insulin resistance, the early teen years would be the time to treat the early development of cardiovascular problems. Wait much longer than the teen years to treat, and it might be too late, according to Nadeau: “Once there’s calcification and hardening of the arteries, we think there could be permanent damage to blood vessels.”
The results are measurable. “Kids don’t have heart attacks or strokes, so we don’t have hard evidence. But we see the early signs already in teenagers,” Nadeau says. “They’re old enough that we can find something, but young enough that the changes haven’t become permanent.”
Nadeau is conducting a study to see if metformin, a drug commonly used to treat insulin resistance in people with type 2 diabetes, may be effective at warding off heart disease in teens with type 1. Here’s how it works: She’s recruiting 60 teens with type 1 diabetes. She and her team bring them into the hospital for a round of tests, looking at their heart and arteries using MRI scans and echocardiograms. The researchers will look at neck and arm blood vessels to see how well they open and close and how stiff they are. The teens then spend the night in the hospital and undergo a test to see how insulin resistant they are first thing in the morning.
Next, they’re sent home and asked to take a pill each day. Half get metformin, and half get a placebo. The teens come in for checkups every six weeks for three months. (It’s hard to get kids to stick with a study for much longer, Nadeau admits.) The goal is to see if the group on metformin shows fewer signs of cardiovascular damage at the end of the three-month study.
Evidence that metformin is effective in staving off short-term cardiovascular changes in the teens might lead to a new way to treat heart disease among people with type 1 diabetes by addressing it long before it becomes permanent. “As adults, people with type 1 diabetes have more heart disease,” Nadeau says. “The goal is to find ways to reverse early heart disease by starting younger.”
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