January 2005 - Reduced blood concentrations of a protein called adiponectin appear to indicate a significant risk of cardiovascular disease in one of the first studies to focus on risk of the disorder among patients with diabetes mellitus type 1, previously known as juvenile diabetes. Recent studies suggest that adiponectin, a protein specific to fat tissue, is involved in obesity, diabetes and heart disease.
Results of the study are published in the January issue of Diabetologia, a leading journal affiliated with the European Association for the Study of Diabetes.
"Most studies looking at adiponectin concentrations have been in the non-diabetic population or in people with type 2 diabetes," said Trevor Orchard, M.D., professor of epidemiology, medicine and pediatrics at the University of Pittsburgh Graduate School of Public Health (GSPH) and senior author of the study. "Given our previous work linking insulin resistance to heart disease in type 1 diabetes, we wanted to evaluate whether adiponectin levels in these individuals might be predictive of future cardiac events." Adiponectin has been closely linked with insulin resistance, a known risk factor for heart disease.
Adiponectin is one of the most abundant circulating proteins in human plasma, explained Dr. Orchard, who also is medical director of the nutrition lipid program at the University of Pittsburgh Medical Center, a clinic to which doctors refer patients with lipid metabolism disorders. "Adiponectin also seems to act as an anti-inflammatory molecule," he said.
Investigators found that for people with type 1 diabetes, decreased concentration of adiponectin was associated with increased risk for coronary artery disease (CAD). "Interestingly, this effect was independent of conventional risk factors such as smoking, cholesterol levels or body weight," said research associate Tina Costacou, Ph.D., the study's first author. "Remarkably, it also was a better predicter than our markers for inflammation and insulin resistance, as well as other factors."
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For the newest evaluation, participants were identified from the Pittsburgh Epidemiology of Diabetes Complications Study, a 10-year prospective follow-up study of childhood onset type 1 diabetes mellitus. In the study, patients with CAD were matched with controls who did not have heart disease. Blood samples from 28 cases and 34 controls were matched for gender, age and duration of diabetes.
"Regardless of CAD status, higher levels of adiponectin were observed among female participants in comparison to their male counterparts," said Dr. Costacou, explaining that adiponectin levels in blood samples from women averaged 20.8 micrograms per milliliter, versus 16.5 micrograms per milliliter for men. "This is a significant difference," she said.
Even independent of gender, however, results of the Pittsburgh study suggest that adiponectin has a substantial protective role against CAD. "There was a remarkable 63 percent reduction in risk of CAD for each 6.3 microgram per milliliter increase in serum adiponectin levels," said Dr. Orchard. "These results are striking despite the relatively small number of patients in the study. Our results � the first to show such a strong predictive power for heart disease prospectively in any population � raise the possibility that adiponectin concentration may prove not only a useful marker of cardiovascular risk, but also a potential therapeutic agent for prevention, particularly among high-risk individuals."
The study was funded by the National Institutes of Health. In addition to Drs. Orchard and Costacou, other authors are J.C. Zgibor, Ph.D., and R.W. Evans, Ph.D., both of GSPH; J. Otvos, Ph.D., LipoScience, Raleigh, N.C.; M.F. Lopes-Virella, M.D., Ph.D., Medical University of South Carolina; and R.P. Tracy, Ph.D., University of Vermont.
Source: University of Pittsburgh Medical Center
