Diabetes Forecast

Sizing Up Type 2 Diabetes in Kids

Identifying links to fatty liver disease and type 2

By Andrew Curry , ,

Sonia Caprio, MD

Sonia Caprio, MD
Endocrinologist, Yale University School of Medicine
ADA Research Funding
Amylin Pharmaceuticals Distinguished Clinical Scientist Award

As obesity has risen among America's children, so have related diseases, from high blood pressure to type 2 diabetes. Doctors are also noticing a rise in the number of children with a buildup of fat in the liver that can make it hard for the body to respond to insulin and may contribute to the early onset of type 2.

Called fatty liver disease, the phenomenon is often seen in obese adults, and researchers think that 4 out of 5 adults with diabetes have high fat content in their livers. The consequences for children are still not well understood. Sonia Caprio, a researcher at the Yale University School of Medicine's pediatrics department, is looking at what the liver damage means for developing young bodies. "Their livers look like those of heavy drinkers, but obviously they're not," she says.

Because the liver plays such an important role in regulating the body's levels of everything from blood glucose to fat, researchers think that fatty liver disease could be one reason kids are developing type 2 diabetes younger than ever.

Obesity contributes to fatty liver, which in turn makes it more difficult for the body to respond to insulin, a condition known as insulin resistance. The harder the body's insulin-producing cells must work, the sooner they wear out—leading, in the end, to the onset of type 2 diabetes. One recent study suggests that type 2 now makes up a third of diabetes cases in Americans under the age of 19.

Yet Caprio's research has shown that not all obese children have fat in their livers. With the help of a grant from the American Diabetes Association supported by Amylin Pharmaceuticals, she's trying to figure out whether there's a way to predict which children are more likely to develop type 2 diabetes. Working with the Yale Pediatric Obesity Clinic, Caprio recruited 85 obese children. "We know a lot about their metabolism—we know if they have diabetes, if they have high cholesterol, their body fat distribution," Caprio says. The goal was to see if the kids in the study with fatty livers had anything else in common.

This was no fishing expedition: Caprio was looking for something in particular. Thanks to data gathered in studies on mice, researchers now think there's something in fat cells themselves that can make a person more or less likely to develop fatty liver disease. "Almost 50 percent of the country is now obese," Caprio says. "We need to know why certain obese kids or adults are more at risk."

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Caprio wondered if there might be a connection between the layer of cells under the skin that store energy in the form of fat—the so-called subcutaneous fat—and fatty liver disease. Subcutaneous fat serves an important purpose. It's like the body's gas tank, storing energy for later use.

But sometimes the specialized cells under the skin don't store fat the way they should, and the body starts searching for alternative places to put it. "You're trying to accommodate extra calories, and if you're at maximum capacity, you store it elsewhere," Caprio says. "That elsewhere, unfortunately, is the liver."

That's a problem, because not all fat is created equal. Subcutaneous fat is fairly harmless; fat deep inside the body—in or near organs such as the heart or liver—is not only harder to lose but can contribute to other conditions. "There's very good data from animal studies that it's not overall fat that's related to insulin resistance but where the fat is located," Caprio says.

So what was to blame for the fatty livers of the children in Caprio's study? To find out, she had a plastic surgeon take a tiny sample of flesh, no bigger than a pea, from the bellies of 18 of her patients. She then looked at the way the fat cells were interpreting the information encoded in their genes.

Patients with fatty liver, it turned out, had certain genetic "expressions"—also called polymorphisms—in common. "We found they're unable to store fat in subcutaneous tissue," says Caprio. "There's a genetic component to it. If you have one of these polymorphisms, the fat content of your liver tends to be higher."

Knowing what genetic markers make fatty liver disease more likely is a step forward. "We're trying to understand the bottom line—why certain kids are more prone to diabetes," Caprio says.



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