A mutant rat that mimics a 400-pound human is helping scientists understand early vascular changes that make walking a pain for more than 2 million Americans.“Everybody knows that obesity eventually causes diabetes and that when you have complications of the disease, you may even die,” says Dr. David W. Stepp, cardiovascular researcher in the Medical College of Georgia Vascular Biology Center.“What is underappreciated … is that there are vascular changes and cardiovascular effects of obesity well before you become diabetic.”The Obese Zucker rat model shares the symptoms of obesity with a growing number of Americans. “For example, these animals are glucose intolerent, slightly hypertensive and showing protein in their urine. They have kidney dysfunction even though they are not yet diabetic,” he says.That is because small blood vessels in their kidneys already have begun to fail. All the fat rats eventually will get diabetes, but these ailing animals still have the same blood glucose levels as their lean peers. “When they go into frank diabetes, that pushes their kidneys over the edge. The goal of our lab is to use this model to examine vascular disease in other organs, especially the limbs.”Dr. Stepp recently received a $1.4 million grant from the National Heart, Lung and Blood Institute to study these early vascular changes, called peripheral vascular disease, that can result from obesity, smoking and inactivity.His goal is to prevent a common condition with significant quality-of-life consequences. “The reason peripheral vascular disease is of interest to us is not because it kills but because patients with it often have quality of life indices worse than those of terminal cancer,” Dr. Stepp says. “They can’t walk. They don’t have any mobility. They are not free. They feel humiliated and miserable.”
