Overview

How does resistance to insulin develop in the body? No one knows for sure, but the answer is critical to a growing number of type 2 diabetics.

Seen most often in conjunction with excess weight and inactivity, insulin resistance leads to the body’s inability to regulate sugar in the bloodstream. The result is type 2 diabetes. Complications include heart disease, stroke, kidney disease, nerve damage and blindness, making it a significant health problem in the United States.

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. Research by Jürgen Naggert, Ph.D., investigates the basic mechanisms of the genetics behind obesity and type 2 diabetes susceptibility.

Research

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," said 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."

To further complicate efforts to understand how obesity is linked to diabetes, mouse models developed at The Jackson Laboratory show that there are 500 to 1,000 genes that, when mutated, will lead to obesity.

Naggert and co-investigator Patsy Nishina, Ph.D., are making use of a new mouse model they have developed to explore the genetics inherent in the linkage between obesity and type 2 diabetes, a condition some researchers have termed "diabesity."

"Because type 2 diabetes occurs within the context of obesity and genes associated with insulin resistance have to interact with pancreatic genes, few mouse models for type 2 diabetes exist," Nishina said. "We have developed a new inbred strain of diabetic mice called 'Tallyho.' This new model for type 2 diabetes is characterized by moderate obesity, excessive levels of insulin in the blood, glucose intolerance and enlargement of pancreatic function associated with insulin production. Male Tallyho mice become overtly diabetic at eight weeks of age, which is the equivalent of a young human adult."

Resources

• Current diabetes research (ADA)
• U.S. Centers for Disease Control and Prevention
• Maine Center for Disease Control and Prevention
• Joslin Diabetes Center
  
• Diabetes Action: Research and Education Foundation
• Diabetic Exercise & Sports Association
• Mendosa.com - Writer specializing in diabetes, comprehensive list of diabetes resources
• American Diabetes Association (ADA)
  • Current type 2 diabetes research (ADA)
  • The genetics of Diabetes (ADA

Personal Connections

Frankie Barnhart is too well acquainted with the consequences type 2 diabetes can have. Her grandfather lost a leg to complications of diabetes. Her father is battling kidney failure from diabetes. Her daughter is pre-diabetic at age 20. And she herself was diagnosed with type 2 diabetes two years ago.

Frankie is lucky. While working until recently in the employee health center at The Jackson Laboratory as a medical assistant, she was under skilled medical care. That, combined with attention and diligence on her part, allowed her to avoid the worst complications of the disease. But she isn't free from worry.

"I manage my diabetes with diet, exercise and daily metformin (a common type 2 diabetes drug)," Frankie says. "Due to a congenitally small kidney and diabetes I’m afraid, because I am at a higher risk for kidney failure."

The type 2 diabetes epidemic is getting worse, and not everyone receives the care needed. For those who are particularly susceptible, like Frankie’s daughter, it can be a medical problem that lasts a lifetime.

"My hope is that research today will help my daughter and others like her by preventing or curing diabetes in the future," says Frankie, "not just manage it, like I do."