CLINICAL RESEARCH
Identifying Strategies That Improve Outcomes
Long-term complications significantly impair the health of people with diabetes. The risk of having a stroke or dying from heart disease, for instance, is two to four times greater in people with diabetes. Diabetes is also the leading cause of blindness in working-age adults and a major cause of kidney disease requiring dialysis or transplantation.
More than 25 clinical trials are under way at any given time at Joslin, ranging from studies of promising new drugs to those evaluating the impact of lifestyle changes such as weight loss and increased physical activity on the prevention or treatment of diabetes and its complications.
Targeting Cardiovascular Disease
A number of studies under way in the section aim to identify the best strategies for improving the long-term health of participants. These studies focus particularly on finding ways to prevent cardiovascular disease.
One example is the Diabetes Prevention Program Outcome Study (DPPOS), a major multicenterclinical trial. An earlier study, the Diabetes Prevention Program, showed that treatment with the blood glucose-lowering medication metformin and a combination of diet and exercise are both effective at preventing the development of type 2 diabetes in people who have insulin resistance and impaired glucose metabolism. Both treatments also reduced the development of the metabolic syndrome, and the lifestyle changes improved both hypertension and lipid profiles, thus reducing the risk of cardiovascular disease. In DPPOS, researchers are now assessing whether metformin and lifestyle changes also can prevent the development of heart attacks, stroke and other long-term complications in this population.
A related investigation, the Look AHEAD (Action for Health in Diabetes) Study, is comparing two interventions to determine which is most effective at preventing cardiovascular and other complications in people who already have type 2 diabetes. Half of the participants are trying to lose 10 percent of their weight and exercise more, while the other half participate in a diabetes support and education program.
To improve early diagnosis of cardiovascular disease, investigators in the section are studying a new technique to gauge the health of blood vessels and arteries. Known as pulse wave analysis, it measures arterial rigidity to determine whether someone has developed atherosclerosis. The technique is now being evaluated for use in a clinical setting to assess an individual’s risk of cardiovascular disease and to evaluate the impact of medications and other interventions on vascular health.
Preventing Vascular Damage
Other investigations aim to prevent the early biological changes that lead to the development of diabetes, and the vascular changes that underlie many different long-term complications. Investigators in the section conduct studies to evaluate whether particular medications or lifestyle changes can improve blood-vessel health and endothelial-cell function—and thereby lower the risk of long-term complications—in people who already have diabetes.
One investigation is evaluating the effects of the medication pioglitazone on improving endothelial-cell function and preserving pancreatic beta-cell function in people with insulin resistance or type 2 diabetes. Another study is evaluating the effects of a new treatment for people with type 2 diabetes, exendin-4 (exenatide, compared to treatment with insulin, on vascular health and reduction of risk factors for cardiovascular disease.
In addition, the section is participating in a multinational trial to determine the relationship between mean blood glucose and A1C levels over a wide range in various racial/ethnic populations, with the long-term goal of establishing a worldwide standard for the A1C assay that can be expressed in terms of average glucose concentrations.
The Joslin General Clinical Research Center (GCRC) is funded by the National Institutes of Health. In 1999, the Joslin GCRC was added as a satellite of the Harvard-Thorndike General Clinical Research Center at Beth Israel Deaconess Medical Center. Investigators representing a wide variety of research interests and expertise use the GCRC, which includes a highly skilled nursing and bionutrition staff to provide patient care and perform research procedures and testing protocols, as well as outpatient physical resources for conducting studies. Additionally, the GCRC provides education and training in patient-oriented research to students, postdoctoral fellows, visiting scientists and other healthcare professionals, and has contributed to two major clinical research core facilities.
Section Investigators:
A. Enrique Caballero, M.D.
Om P. Ganda, M.D.
Allison B. Goldfine, M.D.
Osama Hamdy, M.D., Ph.D.
Edward S. Horton, M.D.
William_C._Hsu,_M.D.
Antoine Kaldany, M.D.
Mark E. Williams, M.D.
Howard Wolpert, M.D.
