PITTSBURGH, April 21 – Insulin resistance, a condition commonly associated with the development of type 2 diabetes, is likely a major cause of heart disease in people with type 1 diabetes, according to study results published by University of Pittsburgh Graduate School of Public Health (GSPH) researchers in the May 2003 issue of Diabetes Care, a journal of the American Diabetes Association.

"Heart disease is a major complication for people with diabetes, including those with type 1 diabetes, and until now there has been no clear explanation for its cause," said principal investigator Trevor Orchard, M.D., professor and acting chair, department of epidemiology, GSPH. "We now suspect that insulin resistance occurs in those with type 1 diabetes in the same way as it does in those with type 2, essentially giving these individuals double diabetes and greatly increasing their risk of heart disease."

Insulin resistance, long associated with type 2 diabetes and a known risk factor for heart disease, occurs when the body does not properly use insulin to metabolize blood glucose, or sugar. The condition results when insulin fails to enable cells to admit glucose, necessary for cells' energy production. Glucose then builds up in the blood, and additional insulin is required. The new study suggests that this condition can occur in people who have type 1 diabetes as well.

"The good news is that not all people with type 1 diabetes are insulin resistant, and for them the risk of heart disease may not be as high," Dr. Orchard said. "Clearly, reducing or preventing insulin resistance through exercise, weight loss and possibly medication may help people with type 1 diabetes avoid heart disease."

The study analyzed data from the Pittsburgh Epidemiology of Diabetes Complication Study (PEDCS), a 10-year prospective investigation based on a cohort of adults with type 1, or childhood-onset, diabetes. Of the 658 subjects in PEDCS, 603 did not have heart disease at baseline and were followed for the current study.

Over the 10-year period there were 108 cardiovascular events such as angina, heart attack or death among the participants. Risk factors were lowest among those who experienced no cardiovascular events, moderate among those with angina and highest among those who died.

Insulin resistance was a risk factor that predicted all adverse events, and it was the most severe among those participants who experienced the most serious events.

To measure insulin resistance, investigators used the estimated glucose disposal rate (eGDR), a novel calculation based on waist-to-hip ratio, hypertension status and long-term blood sugar levels. Study participants with no cardiovascular events had a normal eGDR; those who experienced angina, considered a moderate event, had a lower eGDR; and those with the most severe events had the lowest eGDR.

High blood sugar itself was the only potential risk factor that did not appear to predict cardiovascular events.

"Our analyses are consistent with the hypothesis that individuals with high blood glucose develop plaques in their coronary arteries that are more fibrous than normal. That quality could have a stabilizing effect that makes the plaque less likely to rupture and cause a blood clot that would result in a heart attack," Dr. Orchard explained. "However, any protective effect from the fibrous nature of their arterial plaque is countered by the likelihood that glucose causes more such plaques and that it will not affect the risk of atherosclerosis-related problems elsewhere in the body, where the very existence of plaque can lead to lower extremity arterial disease, which sometimes results in amputation."

The study was supported by the National Institutes of Health.

Established in 1948, the Graduate School of Public Health at the University of Pittsburgh is world-renowned for contributions that have influenced public health practices and medical care for millions of people. For more information about the GSPH, access the school's Web site at http://www.pitt.edu/~gsphhome.