New test predicts complications in diabetes

September 26, 2000

May point to new treatments

HAIFA, Israel, and NEW YORK, N.Y., September 26, 2000 -- A new and simple blood test pinpoints which diabetes patients are most likely to develop crippling and life-threatening complications that damage the heart, eyes and kidneys. The test, developed by Andrew P. Levy and colleagues at the Technion-Israel Institute of Technology in Haifa, will provide guidance to doctors in choosing the proper treatment for each patient.

As well, the research that underlies the test may indicate a route to new and more effective treatments that prevent these complications. The work is reported in related articles in the September 28 issue of the New England Journal of Medicine and in the September 13 Journal of the American Medical Association.

The new blood test determines which type of a certain protein called haptoglobin patients carry in their blood. Those who carry one type of haptoglobin have a low risk for developing complications, while those carrying the two other types have much higher risks.

"The reason that some diabetic patients develop serious life threatening complications while others appear to be relatively immune from them has puzzled us for years. This exciting work sheds light on this question and has important implications for the care of patients," said Eugene Braunwald, professor of medicine at Harvard Medical School and V.P. for Academic Programs, Partners HealthCare Systems, Brigham and Women's Hospital.

"Diabetes is a leading cause of blindness in this country," said Robert Sherwin, MD, President of the American Diabetes Association. "If we can pinpoint at an early stage those predisposed to retinopathy, we can then introduce intensive treatments early to reduce or eliminate the onset of blindness." He added that the benefits from identifying patients predisposed to kidney and vascular disease will be equally significant.

Diabetes -- characterized by high blood sugar concentrations resulting from the body's inability to produce insulin or use it effectively -- affects about 16 million people in the U.S., claims close to 200,000 lives each year and more than $100 billion annually, according to the American Diabetes Association. It can lead to complications including blindness, kidney disease and heart disease. Although insulin injections can help bring glucose or blood sugar levels down, currently it is impossible to effectively substitute for a healthy body's control of glucose, so diabetics suffer from frequent periods of high blood sugar.

High blood sugar has been thought to produce the free radicals that damage cells and destroy kidney function, cause the buildup of plaques that constrict heart arteries, and damage the retina of the eyes. Not all diabetes patients suffer these severe complications, and Levy's research was aimed at finding out why some do, and to predict which ones.

"We focused not on glucose-produced free radicals, but on a second source of these radicals -- the hemoglobin in red blood cells," says Levy. Inside red blood cells, hemoglobin performs the essential task of carrying oxygen. But when the cells die and break open, the loose hemoglobin rapidly produces free radicals. To prevent this, the body produces a protein called haptoglobin, a scavenger molecule that binds with hemoglobin floating free in the blood and renders it harmless.

In about 20 percent of individuals, this hemoglobin clean-up is more effective than in others, because these individuals produce a form of haptoglobin that is relatively small and can seek out the hemoglobin in the nooks and crannies of the circulatory system. Other people produce two larger forms of haptoglobin that are less effective. The form produced is genetically determined.

"We thought that since diabetics' bodies were already stressed by trying to clean up the free radicals created by high glucose levels, the additional radicals coming from ineffective scavenging of hemoglobin could tip the balance and cause the tissue damage that leads to complications," Levy says. That is exactly what they found in their studies -- in dramatic fashion.

Levy's team used a blood test to distinguish among the three types of haptoglobin in 53 diabetic patents. Of those patients who had the two less effective types of haptoglobin, 60% suffered from retinopathy (eye damage), 34% from nephropathy (kidney damage) and 83% from restenosis (recurrent heart disease). Of those patients who had the more effective type of haptoglobin, none suffered from nephropathy or restenosis and only one of 12 had retinopathy.

Since haptoglobin type is determined genetically and does not change during life, physicians can use a haptoglobin test to see who is at high risk for complications and who is not. This will benefit patients, since it will allow doctors to treat those at risk for complications more aggressively, while treating more conservatively the minority protected by their haptoglobin type.

As important, the research shows that the level of free radicals in the blood stream has a major impact on the complications of diabetes. "This suggests that drugs that reduce free radicals will help prevent complications, and there is a good chance of finding such drugs," Levy points out.
The Technion-Israel Institute of Technology is Israel's leading scientific and technological center for applied research and education. It commands a worldwide reputation for its pioneering work in computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel's high-tech companies are Technion graduates. The Technion's 19 faculties and 30 research centers and institutes in Haifa are home to 13,000 students and 700 faculty members.

Based in New York City, the American Technion Society is the leading American organization supporting higher education in Israel, with more than 20,000 supporters and 17 offices around the country. Technion societies are located in 24 countries around the world.

Martha Molnar

American Society for Technion - Israel Institute of Technology

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