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Dr. Massimo Pietropaolo — Bringing Excitement to the World of Type 1 Diabetes Research

Each year in the U.S., 13,000 children, adolescents and young adults are diagnosed with type 1 diabetes. The disease requires daily insulin injections just to stay alive, not to mention the increased chances of future complications such as kidney and heart disease. Imagine the day when this disease can be prevented, saving thousands from a life of injections and future crippling health problems. Dr. Massimo Pietropaolo, a U- M diabetes researcher, is on a mission to bring that day closer.

Dr. Massimo PietropaoloDr. Massimo Pietropaolo

The University of Michigan Comprehensive Diabetes Center welcomed Dr. Massimo Pietropaolo to the organization in 2006. He is a professor of Internal Medicine and professor of Pediatrics and Communicable Diseases. His current research focuses on two goals: predicting and preventing type 1 diabetes; and understanding a form of type 1 diabetes called Latent Autoimmune Diabetes in Adults or LADA, which is diagnosed in individuals who are over 30 years of age – much older than the usual onset of type 1.

Dr. Pietropaolo has a long and impressive career in diabetes research and care. He received his medical degree from the University of Perugia School of Medicine in Perugia, Italy. It was at this university where he also completed his residency and clinical fellowship in endocrine and metabolical sciences. A recipient of two Juvenile Diabetes Research Foundation fellowhips, Dr. Pietropaolo went on to be a research fellow under Dr. George Eisenbarth in the section of Immunogenetics at the Joslin Diabetes Center at the Harvard Medical School. He continued with Dr. Eisenbarth at the Barbara Davis Center for Childhood Diabetes at the University of Colorado Health Sciences Center. Before coming to Michigan, he was an associate professor of Pediatrics, Medicine and Immunology at the University of Pittsburgh School of Medicine.

Dr. Pietropaolo’s primary research involves predicting and ultimately preventing type 1 diabetes, especially in blood relatives of type 1 patients because these individuals face a far higher than normal risk of developing the disease. Recently, he and his cohorts developed a combination of old and new testing methods which better predicted who among patients’ siblings, children and cousins will develop the disease.

Old testing methods date back to the 1970s when researchers first identified islet cell antibodies. Islet cells are located in the pancreas and make hormones such as insulin. In type 1 diabetes, the immune system produces antibodies that cause the body to attack good islet cells as though they were foreign substances eventually killing them and causing diabetes. Without the insulin produced by some islet cells, the body cannot break down sugar for energy. Researchers were able to measure the level of these antibodies to predict the likelihood of developing type 1 diabetes. However, the accuracy rate was less than ideal.

Newer tests involve biochemical markers to uncover islet autoantibodies. These autoantibody responses suggest a relationship between type 1 diabetes and the body’s attack against pancreatic insulin producing cells.

"In the mid 1990s, we found that a combination of autoantibodies could predict type 1 diabetes over time in individuals at risk of developing the disease," states Dr. Pietropaolo. "However, there were some patients who were positive for a combination of these biochemical markers that did not develop type 1 diabetes."

So, Dr. Pietropaolo and his team decided to combine the old and new testing methods. They measured both types of antibodies in approximately 1,500 close relatives of patients with type 1. This test led to the highest level of accuracy ever achieved in predicting type 1 diabetes.

Being able to predict the level of risk is the first step; the next is to do something with that information and prevent diabetes from occurring. Dr. Pietropaolo and his team are currently working to determine if they can block the immune system’s anti-islet cell attack by encouraging the growth of immune system cells that counteract the attack. The research is still being performed in rodents, but a clinical trial may be ready to start as early as 2007. In the meantime, the U-M is preparing to take part in national clinical trials of drugs that dampen the immune system reaction. Such drugs may be promising but carry a burden of long-term side effects.

Dr. Pietropaolo also is involved in the study of Latent Autoimmune Diabetes in Adults. This form of diabetes has often been referred to as “Slow Onset Type 1 Diabetes.” Patients with LADA are mistakenly thought to have type 2 diabetes because of their advanced age at the time of diagnosis (30 or older). Amazingly, it is thought that 10 to 15 percent of people affected with type 2 diabetes have this form of autoimmunity. If this percentage is correct, 2 million Americans might have an unidentified autoimmune form of type 2 diabetes, prevalence higher than that of recent onset childhood diabetes.

For clinicians, accurately distinguishing type 1 from type 2 diabetes allows for the initiation of appropriate medical treatment. The correct classification could also allow immunity-based therapeutics to be instituted sufficiently early in a large number of patients otherwise diagnosed as having type 2 diabetes. This could possibly delay the onset of insulin dependence and complications due to elevated blood sugar levels.

The University of Michigan is privileged to have Dr. Pietropaolo part of their diabetes research team.   He is bringing excitement to the world of type 1 diabetes research.