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Diabetes Genes

By David Mendosa

Last Update: August 17, 2005

Trying to understand the cause of diabetes is like peeling an onion. Not only do both activities tend to make us cry, but also as soon as we reach one layer, there's another one to cut through.

Only recently have we begun to glimpse the core. In the case of diabetes the core consists of both some little things called genes and a huge thing called the environment.

Finding the genes is quite a challenge

On the surface, all types of diabetes have one thing in common. Our bodies can't do a good job of using the food we eat. This is because of a disturbance of carbohydrate metabolism.

Below the surface of this disturbance is an insulin problem. For glucose to get into our cells, it needs insulin, which is a hormone that the beta cells in our pancreases produce. Those of us who have type 1 diabetes aren't producing any insulin and require supplemental shots.

Type 2 diabetes results from two problems. Our pancreases may be fatigued but they are still producing some insulin. At the same time our cells are resistant to the insulin that the beta cells are pumping out. This leads to too much glucose in our blood.

But what is causing these problems with insulin? The answers are beginning to appear from genetic studies around the world. These studies show that some—but not all—of the fault lies in our genes. In fact, "diabetes is probably the most common genetic disease that we have," says Jerrold M. Olefsky, M.D., of the University of California, San Diego.

Our environment also plays a role. In other words, it's nature and nurture.

Contrary to the expectations of most researchers, genetics is more of a problem with type 2 diabetes than it is with type 1. Some of the best evidence for this comes from studies of identical twins.

If one identical twin has type 2 diabetes, the chance of the other twin having it is 60 to 90 percent. In contrast, if one identical twin has type 1 diabetes, the chance of the other twin developing it is about 50 percent, according to Alan Shuldiner, M.D., of the University of Maryland School of Medicine.

If both of your parents have type 2 diabetes, you have about a 40 percent chance of getting it yourself, Dr. Shuldiner says. And if one parent has it you have about a 20 percent chance.

That's a bit higher than the 10 to 15 cited by the Genetic Health Web site at What Is Type 2 Diabetes? for a parent or sibling with the disease. For people with type 1 the risk is about two percent if your mother has diabetes and six percent if your father or siblings have Type 1 diabetes, according to What is Type 1 Diabetes?

Finally, genetic differences explain different prevalence rates for type 2 diabetes. These rates range from 5 to 8 percent for Caucasians to 50 percent for Pima Indians in Arizona, Dr. Shuldiner says.

With all the research on genes now underway, finding the diabetes gene should be easy—if there were just one. That's true for only 2 to 5 percent of people with type 2 diabetes, mostly those with maturity onset diabetes of the young (MODY) and maternally inherited diabetes and deafness (MIDD), according to M. Alan Permutt and Andrew T. Hattersley, "Searching for Type 2 Diabetes Genes in the Post-genome Era," in the November issue of Trends in Endocrinology and Metabolism.

For the rest of us diabetes seems to result not only from the combined working of several genes but also from a variety of environmental factors. Finding the genes is quite a challenge, as they point out.

"Considering that perhaps 50,000 to 100,000 genes might exist, their multiple forms and the fact that genetic variation in the disease might be due to many genes, each with modest effect, illustrates the magnitude of the problem in the search for T2DM genes," they write.

More and more type 2 diabetes genes are coming to light. Perhaps 20 have been identified. DNA Sciences lists about half of these.

The most exciting recent discovery was the September announcement of a gene scientists believe increases the risk of developing diabetes by 300 percent. The discovery of this "calpain-10" gene could lead to better prevention and treatment of type 2 diabetes. Will this lead to a cure? We'll know when we reach the core. 

The American Diabetes Association originally published this article on its Web site as one of my “About the Internet” columns.

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