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Trevor Orchard

University of Pittsburgh Schools of the Health Sciences

University of Pittsburgh Researchers Devise Simple Insulin Resistance Test to Predict Heart Disease in Type 1 Diabetics

PITTSBURGH, March 23, 2000 — A simple series of questions and measurements to determine insulin sensitivity could help save the lives of many people with type 1 diabetes by identifying those who are at an increased risk of heart disease. The new test is described by researchers from the University of Pittsburgh Graduate School of Public Health and the School of Medicine in a paper published in the April issue of Diabetes, a journal of the American Diabetes Association.

Dubbed the Insulin Resistance Syndrome (IRS) score, the test is a clinical means of measuring insulin resistance, a condition that researchers believe may be common, but often overlooked, in patients with type 1 diabetes. In the past, insulin resistance has been associated only with type 2 diabetes.

In type 1 diabetes, which affects 10 to 15 percent of all diabetics, the pancreas cannot make insulin to regulate blood glucose. The condition often develops in patients before the age of 30 and requires insulin therapy.

Insulin resistance occurs when the body does not properly use insulin to metabolize blood sugar. To compensate, the body produces more insulin and results in an oversupply.

Insulin resistance is associated with an increased risk of coronary artery disease, a leading cause of mortality in people with type 1 diabetes. With the new IRS score, physicians can identify insulin resistant patients and begin heart-saving treatment interventions including exercise, weight loss and medication.

"Insulin resistance has long been recognized in type 1 diabetes, but few studies have examined the association between clinical IRS risk factors and insulin resistance in this population," said Trevor J. Orchard, M.D., professor of epidemiology at GSPH and senior author of the article.

This study is the first to develop a method of estimating a patient’s insulin sensitivity and validating it with the use of the insulin clamp, a three-hour test during which glucose and insulin are administered intravenously and adjusted to achieve stable blood glucose levels. The clamp measures an individual’s glucose disposal rate (GDR). A low GDR shows that the body is not using insulin effectively to process glucose, indicating insulin resistance.

"Up until now, the clamp has been the most accurate means of determining insulin resistance, but it is used only in research because it is expensive and time consuming," said Katherine V. Williams, M.D., M.P.H., University of Pittsburgh, division of endocrinology and metabolism, and clinical investigator on the study. "But our research study has shown that the IRS score is a good proxy measure, and the beauty is that it is not costly, intimidating, invasive or time consuming."

The IRS score is based on clinical risk factors in adults with type 1 diabetes, including hypertension, high waist-to-hip ratio, family history of type 2 diabetes and glycemic control. By applying a personalized rating of 1 (lowest) to 3 (highest) for each risk factor, then dividing by the total number of risk factors for which data are available, a physician can calculate an IRS score for the patient.

The study included eight type 1 diabetic patients from each of three IRS risk categories—low, moderate and high. The subjects received a clamp study to measure GDR and thus verify their IRS scores.

Results showed an inverse correlation between participants’ IRS risk group and mean glucose disposal rate (GDR). Subjects with low IRS scores showed high GDR, and those with high IRS scores showed low GDRs. Researchers found high waist-to-hip ratio to be the strongest predictor of insulin resistance. High-density lipoprotein (HDL) and triglyceride levels were analyzed as well but made little difference in the IRS score.

"Previous research has identified a family history of type 2 diabetes as a risk factor for insulin resistance in the general population, but this is among the first to identify it as a risk factor in type 1 diabetics," said Dr. Orchard. Research also has found that a family history of type 2 diabetes increases the risk of cardiovascular complications.

The study was funded by the National Institutes of Health and the General Clinical Research Center at the University of Pittsburgh Medical Center.

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