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Type 2 diabetes researcher receives prestigious award
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AUSTIN, Texas — At the American Association of Clinical Endocrinologists Annual Scientific and Clinical Congress, Ralph A. DeFronzo, MD, BMS, MS, BS, received the American College of Endocrinology’s Distinction in Endocrinology Award.
The award recognizes an AACE member who is expanding the field through education and research.
Endocrine Today spoke with DeFronzo, deputy director of the Texas Diabetes Institute and chief of the diabetes division at the University of Texas Health Science Center, San Antonio, about his work with combination therapy for the treatment of type 2 diabetes and his future hopes for the field.
What area of endocrinology most interests you right now and why?
DeFronzo: My major interest focuses on the pathophysiology of type 2 diabetes at the whole body, organ, cellular and molecular levels, and the development of novel therapeutic interventions that correct the multiple pathophysiologic disturbances present in the disease. I am convinced that, in order to successfully restore normoglycemia, we need to use combination therapy with multiple agents to correct the myriad pathophysiologic disturbances that are present in people with type 2 diabetes. To change the “treat-to-fail” stepwise approach, we have initiated clinical trials using state-of-the-art methodologies to establish the benefit of early combination therapy.
What has been the greatest challenge in your prof essional career thus far?
DeFronzo: I am an out-of-the-box, creative thinker and continue to be amazed at how refractory clinicians and scientists in the diabetes community are to accept novel ideas that challenge “established dogma.” It took decades of work by Gerald M. Reaven, MD, and myself before insulin resistance was accepted as a major pathophysiology disturbance in type 2 diabetes. The concept of combination therapy at the time of type 2 diabetes diagnosis has yet to be accepted, and we continue to employ the “treat-to-fail” stepwise approach with medications that do not correct the basic pathophysiologic defects present in type 2 diabetes. From the time of our original description about the ability of SGLT2 inhibitors to improve glycemic control by enhancing renal glucose excretion and reversing the glucotoxic effect of hyperglycemia on insulin sensitivity and insulin secretion, it took 20 years to get this class of drugs approved for the treatment of patients with type 2 diabetes.
What do you think will have the greatest influence on your field in the next 10 years?
DeFronzo: I believe that the development of an effective means of beta cell-replacement therapy will be the next major advance in the treatment of both type 1 and type 2 diabetes. I am skeptical that this can be achieved via islet transplantation or stem cells. Rather, it will require innovative approaches such as reprogramming cells in the pancreas to secrete insulin in response to minute-to-minute fluctuations in the blood glucose concentration, an approach that we currently are working on.
What are the most exciting advances that you have been a part of?
DeFronzo: The development of the euglycemic insulin and hyperglycemic clamps, which today remain the gold standards for quantitating insulin action and insulin secretion, respectively, was a major advance that allowed me to elucidate the pathophysiologic disturbances responsible for type 2 diabetes and establish insulin resistance as a hallmark feature of the disease. These in vivo techniques have played a major role in the development of novel therapeutic interventions for the treatment of people with type 2 diabetes. Working with Gerard L. Daniel, MD, of Lipha Pharmaceuticals, I served as the lead investigator for the studies that led to the eventual approval of metformin by the FDA (De Fronzo RA, et al. N Engl J Med. 1995;doi:10.1056/NEJM199508313330902). This was the first new drug introduced into the U.S. market since the sulfonylureas. My work also has played a major role in defining the mechanisms of action of the thiazolidinediones and glucagon-like peptide 1 receptor agonist class of drugs, while the use of phlorizin led to the development and eventual FDA approval of the SGLT2 inhibitor class of drugs. As a champion for early combination therapy in patients with newly diagnosed type 2 diabetes, I hope that our clinical studies will render the “treat-to-fail” approach obsolete.
What are your hobbies/interests outside of work?
DeFronzo: I enjoy travel, which allows me both to experience other cultures and to disseminate the knowledge of diabetes that I have accumulated as a clinician and basic science/clinical investigator. My main hobby is golf and I am proud that I have been able to shoot my age. However, I’m not sure whether this reflects an improvement in my golf game or advancing age. I’m still waiting for the elusive hole-in-one. – by Cassie Homer
Disclosures: Defronzo reports various financial ties with Astra Zeneca, Boehringer-Ingelheim, Elcelyx, Janssen, Novo Nordisk and Takeda.