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Study shows Type I Diabetes is genetic disease

By Bill Scanlon, Rocky Mountain News (Contact)

Published December 29, 2008 at 3:14 p.m.
Updated December 29, 2008 at 3:14 p.m.

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A 40-year study of identical twins at the Barbara Davis Center for Childhood Diabetes is finding that four out of five people eventually develop the disease after their identical twin gets it first.

But the time lapse before the second twin gets it can be 10, 30 even 50 years.

"This study is telling us that Type I Diabetes is primarily a genetic disease," said Dr. George Eisenbarth, who is the Executive Director of the Barbara Davis Center for Childhood Diabetes at the University of Colorado at Denver Medical School.

It's also showcasing the roles several different genes play in diabetes and the steps a family member at risk can take to delay the onset.

"We know Type I diabetes develops because the body's white blood cells attack and kill the cells that make insulin," Eisenbarth said.

The 40-year study and a new one tracing 300,000 children at risk for the disease "tie into our being able to understand how to predict diabetes," he said. "We now have tools to predict and trials to try to prevent Type I diabetes."

Type I diabetes formerly was called Childhood Diabetes, but it can attack at any age and is characterized by the body's inability to produce insulin.

By contrast, Type II diabetes usually is associated with lifestyle, such as obesity, that slows the body's ability to keep blood sugar in balance.

Some 10 percent of the U.S. adult population has one form of the disease or the other.

Dr. Michael Savage's identical twin developed Type I diabetes back in 1974, when they were both 27 years old.

Identical twins have identical genes, so he was certainly susceptible.

"It's not as if it kept me up at night," said Savage, 61, a professor at the University of Colorado at Denver School of Dentistry.

But for the next three decades, his brothers' diagnosis "sort of hung like a sword over my head."

Thirty years later, when he was 57, Savage developed the markers for diabetes. He now gives himself five shots a day to deliver insulin to his body. His body still is producing a bit of its own insulin, unlike his brother, who is completely dependent on injected insulin to keep his blood sugar in balance.

"When they checked me out 11 years ago, and I told them that my twin brother was insulin-dependent, they didn't believe it," Savage said. They brought him in to make sure it was true.

Yes, his twin had it, yet Savage didn't have a trace of the disease.

The doctors at Barbara Davis brought him in yearly for blood-glucose and antibody tests."

Four years ago, Savage turned up positive.

"Before diabetes develops, we can detect antibodies in the blood," Eisenbarth said. Antibodies can precede the actual diabetes by 10 or 15 years -- or maybe by just one year.

"We don't know what the trigger is, after the genetic susceptibility. The first twin might get it at 12, and the second at 60," Eisenbarth said.

Savage now takes low doses of insulin three to five times a day.

He hasn't had to stop skiing or scuba diving, but his diet isn't as fun as it used to be.

"I'm pretty much on a low-carb, high protein diet," he said. "I have to watch my simple carbs -- the white potatoes, the white bread."

Otherwise, "Life is fine," he said. "This is not something I look upon as a death sentence."

Savage said he learned how to deal with his diabetes by watching his brother, Pat, and seeing what not to do.

"He was in denial. He had several episodes of very low blood sugar, passing out, going to the hospital.

"I never have, although I've come close a couple times."

About 2 in 5 Americans carry a gene that makes them at elevated risk for Type I diabetes. But the extreme risk comes when a person has inherited several genes from both mother and father, patterned in a way that make them particularly susceptible.

There has been a tremendous increase in Type I diabetes in Colorado and the nation -- a doubling in just the past 25 years, Eisenbarth said.

"It probably has to do with the environment -- something added or taken away over the last 70 years," he said.

Aside from identical twins, if a sibling has diabetes, the other siblings have about a 1 in 20 chance of getting the disease.

Among people with no family history of the disease, the chances of contracting Type I are less than one in 300.

Some 40 genes are supposed to contribute to diabetes risk. Most of them are on chromosome 6.

The Barbara Davis Center is following 300,000 newborns who have at least one marker for diabetes risk, trying to determine if an environmental trigger causes certain of the children to develop the disease.

The kids enrolled in the study get periodic blood tests to see if their bodies are starting to develop the antibodies to fight diabetes -- usually the first sign that the disease is on its way.

A Colorado child dies of Type I diabetes about once every two years.

Even though the signs of diabetes are dramatic -- thirst, losing weight, passing a lot of urine, vomiting -- the first time a child with diabetes symptoms sees a doctor, the signs more likely than not will be missed, he said.

"It takes just two minutes to check the blood sugar in an ER," he said.

A delayed diagnosis could be fatal.

Animal studies are encouraging, including a vaccine that thwarts the immune system's attack on healthy insulin.

Researchers are working on a new approach in which medicines are infused just once a year to boost the number of regulatory T cells in people at risk for diabetes or autoimmune diseases, while slowing the manufacture of dangerous effector T cells.

"There's a major worldwide effort now to find the set of genes that cause diabetes," he said. "Some day, we hope to be able to screen for diabetes and autoimmune diseases, and develop therapy to prevent the illnesses.

"Human immunology is finally coming of age and attacking these common illnesses," Eisenbarth said. The breakthroughs are a legacy of the Human Genome Project.

"We're trying to delay the progress, but prevention is the goal."

Comments

  • December 29, 2008

    7:25 p.m.

    Suggest removal

    bug writes:

    Hi

    Thankyou for this article...most interesting as the argument regarding Diabetes Type 1 having a genetic predisposition has been raging for a long time.

    Im sure some will still not be conviinced, however a 40 year study cannot be ignored...sheer numbers tell the story.

    I wish the Researchers well and hope they will now go forward and dig deeper to find how having these genes one can end up with Typ1 Daibetes.(what the processes are)

    Eventually we will see a treatment for those who continue to suffer so...though I think it will take perhaps 20 or more years.

    I have realised that all this research costs money and no Pharma is going to want to find THE Cure...so who pays, hopefully Government and the Public will realise that they must pay to fix the problem..

    One thing I will note is that Autoimmune Disease has become an Epidemic...cost to health care is unimaginable all this with little treatment and no cure....forget going back to the moon...this is the hardest thing to do right now....
    find the answer to Autoimmunity.

    I have no doubt that other Autoimmune Diseases will follow a similar pattern which these researchers have realised with Diabetes and Celiac.

    Go guys !

  • December 29, 2008

    11:29 p.m.

    Suggest removal

    Outside_the_Box writes:

    This makes a lot of sense. My grandma and her indentical twin both had diabetes and were diagnosed at the same time around the age of 16. No one else in the family tree is known to have diabetes.