Diabetes: Investigating a “geneticist’s nightmare”

Jackson Laboratory scientists are busy amassing the biomolecular insights essential to heading off the growing, global scourge of Diabetes.

This serious, lifelong metabolic disorder impacts how the body converts digested food into the fuel required for energy and growth. In the United States, where the rate of diabetes has doubled over the last 10 years, diabetes is now an epidemic.

More than 23 million Americans have the disease, with about 1.6 million new cases being diagnosed each year.

The least common—and most serious—form of diabetes is an autoimmune disease. In type 1 diabetes, the body’s immune system attacks and destroys cells within the pancreas that produce insulin, the hormone required to deliver blood sugar to the cells. Type 1 diabetics require daily insulin injections. Also known as “juvenile” diabetes, this life-threatening disease is most commonly diagnosed in children and young adults.

After studying type 1 diabetes at The Jackson Laboratory for 25 years, David Serreze, Ph.D., describes the disease as “a geneticist’s nightmare” by virtue of its complexity.

“Type 1 diabetes involves many, many interactive genes, with 30 to 40 contributing to the disease,” he says. “The highest incidence is among people of northern European extraction, especially those from Finland. As the world becomes a more international place, what happens when a Finn marries a Brazilian in terms of the genomes of their children getting more and more complicated? As these different genetic combinations can contribute to diabetes, the reality of a heterogeneous human population is nightmare number one.”

Type 2 diabetes affects more than 90 percent of people with diabetes. For reasons largely unknown, type 2 diabetics are unable to effectively use the insulin their bodies produce.

This insulin resistance interferes with the conversion of blood sugar into energy, putting type 2 diabetics at greater risk for heart disease, high blood pressure, stroke, kidney disease, nerve damage, amputations and blindness. Should they live long enough, type 2 diabetics eventually become insulin dependent, as are type 1 diabetics.

The role of genetics in the ongoing epidemic of type 2 diabetes is a complex puzzle complicated by the role that genetics plays in another public health epidemic: obesity. The interaction of many genes is associated with the clinical reality that, while about 7 percent of people who are obese develop type 2 diabetes, about 90 percent of those with type 2 diabetes are obese.

“This suggests that, in type 2 diabetics, obesity genes interact with diabetes susceptibility genes to produce the obese/diabetic phenotype that some have termed ‘diabesity,’” says Jürgen Naggert, Ph.D., a Jackson Laboratory principal investigator. “Obesity genes alone would only lead to obesity, while diabetes susceptibility genes alone may not cause this overt phenotype.”