Studies of insulin resistance, development of frontline therapies shape his legacy
SAN ANTONIO (June 11, 2008)—Ralph DeFronzo, M.D., professor and chief of the Division of Diabetes at The University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System, Audie L. Murphy Division, received the American Diabetes Association’s most prestigious award June 8 during the ADA’s 68th Scientific Sessions in San Francisco. The honor is the Banting Medal for Scientific Achievement Award.
Dr. DeFronzo’s innovative thinking and problem-solving capability have made a major impact on international diabetes research and care over the last 38 years. He was the first to prove that individuals with type 2 diabetes are insulin resistant. He led and continues to lead development of new frontline diabetes therapies such as metformin, thiazolidinediones, pioglitazone and exenatide. The latter is based on a compound isolated from the saliva of Gila monsters.
He devised methods to define insulin resistance in the muscle and liver and measure beta cell function (beta cells are the cells in the pancreas that secrete insulin).
In the Banting Lecture, Dr. DeFronzo will propose a new treatment algorithm for type 2 diabetics. In contrast to the current algorithm, which calls for starting a patient on metformin, adding sulfonureas after a time and later starting the patient on insulin, he will advocate the use of triple therapy from the beginning of a patient’s medication regimen. The triple therapy would consist of pioglitazone, metformin and exenatide, each selected for its different, beneficial effects.
“Starting one drug at a time that does not correct known pathogenic abnormalities in type 2 diabetes always fails; it invariably leads to development of diabetes,” Dr. DeFronzo said. “The new algorithm is based on the reversal of established pathogenic abnormalities already present in prediabetic individuals. By the time a person is prediabetic, he has only 20 percent of his original beta cell function, for example. We can’t wait until a person is diabetic to treat the severe beta cell dysfunction that already is well advanced.”
Two of the drugs, pioglitazone and metformin, sensitize the body to insulin, making it more efficient. The third, exenatide, increases insulin reaction by the beta cells and may stimulate the ability of the beta cells to replicate.
The first winner of the Banting Medal was Elliott Joslin, M.D., in 1941. Dr. Joslin was the physician who founded the renowned Joslin Diabetes Center in Boston. In 1971, Dr. DeFronzo’s mentor at Joslin, George Cahill, M.D., won the Banting Medal.
In September, Dr. DeFronzo will be honored in Italy with the Claude Bernard Award, the top award of the European Diabetes Association. This is the first time a single researcher has won both the Banting and Bernard awards in the same year.
Dr. DeFronzo received his M.D. in 1969 from the Harvard Medical School and trained in internal medicine at the Johns Hopkins School of Medicine. He then completed two fellowships—in endocrinology at the National Institutes of Health and Baltimore City Hospitals and in nephrology at the University of Pennsylvania. He was a faculty member at the Yale School of Medicine from 1975 until 1988, when he relocated to San Antonio and the Health Science Center.
He has built the Division of Diabetes to 11 faculty members, and the group has a large clinical research space in the Texas Diabetes Institute (TDI), located in a University Health System facility on San Antonio’s West Side. Dr. DeFronzo is deputy director of the TDI, which provides comprehensive outpatient services for diabetics in the midst of neighborhoods with large Hispanic populations and high numbers of individuals with type 2 diabetes.
“In my opinion, there is no better diabetes center in the world among those that put basic and clinical research together,” Dr. DeFronzo said.
He is an agent for change in the diabetes research field. His ideas have already altered the way type 2 diabetes, in particular, is treated and approached.
“People thought the concept of insulin resistance was ridiculous when we proposed it,” Dr. DeFronzo said. “But I’ve always based what I do on the pathophysiology of the disease. You know what to correct if you know the science of what is happening.”
The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $576 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields. For more information, visit www.uthscsa.edu.