A household name and an all too frequent diagnosis, diabetes tends to mask its seriousness with Americans are fighting type 2 diabetes, the more gradual …
The Diabetes Epidemic:
Navigating the Road to a Cure
A conversation with Denise Faustman, MD, PhD, Director of the MGH Immunobiology Laboratory and David M Nathan, MD, Director of the MGH Diabetes Center
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DiabetesI
S NOT A DISEASE SHROUDED IN MYSTERIOUS SYMPTOMS, EXOTIC ORIGINS OR RARE
occurrences A household name and an all too frequent diagnosis, diabetes tends to mask its seriousness with its commonality One million Americans now are suffering from type 1 diabetes once known as juvenile or insulin-dependent diabetes, in which the bodys immune system damages and permanently disables the pancreas ability to produce insulin And a startling 19 million Americans are fighting type 2 diabetes, the more gradual form of the disease, which first manifests itself when certain cells fail to respond to insulin signals, and eventually results in waning insulin secretion Both forms can result in devastating long-term complications affecting the eyes, heart, kidneys and nervous system Recognizing the urgency of the diabetes epidemic, two world-renowned experts at the Massachusetts General Hospital Denise Faustman, MD, PhD, director of the hospitals Immunobiology Laboratory, and
David M Nathan, MD, director of the MGH Diabetes Center are devoting their careers to understanding, treating and ultimately eradicating this disease that afflicts men and women, adults and children, of all races and all backgrounds Dr Faustman has spent the past decade exploring the calling card of type 1 diabetes: the unwelcome onset of autoimmunity, which attacks the pancreas and its ability to produce insulin Her research culminated in an explosive 2003 discovery: that end-stage diabetes can permanently be reversed in mice through manipulation of their immune systems, and the resulting reappearance of islets groups of cells within the pancreas Dr Faustmans landmark finding raises the enticing possibility that people with type 1 diabetes whose pancreases cannot manufacture insulin might successfully be treated using the same process Dr Faustman currently is aiming to apply the fruits of her research to benefit human patients through clinical trials Dr Nathan is an internationally noted expert on type 1 and type 2 diabetes and their respective complications He has led the development of the modern-day system of diabetes management, and helped to create some of the worlds first
intensive diabetes therapies Dr Nathan chairs the Diabetes Prevention Program, a multi-centered clinical trial sponsored by the National Institutes of Health NIH with the ultimate aim of learning how to prevent type 2 diabetes Already, the trial has revealed that even the patients who are most likely to develop type 2 diabetes can delay its onset through regular exercise and moderate weight loss Vision spoke with these dedicated physician-scientists about their perceptions of the past, present and future in the fight against diabetes
Vision: What drew each of you to the field of diabetes research? Dr Nathan: Really, it was the goal of translating basic science and clinical science into patient care Diabetes is a perfect fit in that respect, and thats the goal of the MGH Diabetes Center today When I first started the center in 1980, the aim was to build a facility in which the most cutting-edge clinical research could be performed and, in turn, to bring the latest developments in research to patient care This integrated
model of clinical research and clinical care has resulted in a highly productive center, where patients volunteer for studies that improve care, and then reap the
benefits of our discoveries Dr Faustman: When it came time to finish my PhD, I knew I wanted to do something that would apply to people Diabetes could best be translated to research; the basic science application was clear-cut and compelling I was recruited to the MGH out of medical
school, and at that time, I was already working on getting insulin-producing cells out of the pancreas The hospital wanted to set up a lab to further that research, and Dr Nathan and I established the first lab in New England to isolate islets for human transplantation However, I realized I had to, and wanted to, go back to the bench to address the fundamental immunologic origins of the disease, and thats what Ive been doing for the past 15 years
Vision: How is the MGH uniquely positioned to advance the best research and care for diabetes patients? Dr Faustman: The MGH is the first institution in the world to bring forth the concept of curing type 1 diabetes by taking advantage of the ability of native islets, or islets developing from other cells, to proliferate and provide insulin once the autoimmune process is interrupted The rest of the type 1 diabetes world was focusing on how to prevent the
disease, or on islet transplantation using major immunosuppressive drugs The concept that islets could recover
I realized I had to, and
wanted to, go back to the bench to address the fundamental immunologic origins of the disease, and thats what Ive been doing for the past 15 years
– Dr Faustman
their function, or even regenerate altogether, wasnt on anyones radar screen Today, there is great interest in whether regeneration can work to cure diabetes, as well as other diseases Dr Nathan and I are great friends We work together to get the job don 
e, and
Dr Denise Faustman
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patients with diabetes were faced with kidney disease, eye disease, amputations and other complications Now, although we havent eradicated the sometimes terrible toll that accompanies long-term diabetes, most patients face a much brighter future We have helped develop new treatments, and have demonstrated the benefits of controlling specific risk factors Now, severe complications are the exception, not the rule We also have shifted our attention Dr Faustman: Part of the preparation needed to proceed with clinical trials, which will try to cure type 1 diabetes in humans, has been the development of
critical tests to gauge the level of autoimmunity Although the technical aspects of developing these specialized tests are difficult and frustrating, I am motivated by the enthusiasm that our research volunteers show at every step of the process People with type 1 diabetes come to our center from all over the world to donate the blood we need to perfect these assays A young man hitchhiked and skateboarded all the way from Utah, and a girl got a ride from Seattle with a trucker service just to help us with our work These people come with the hope that someday the research we do may free them, or others, from the burden of diabetes We cant be certain whether the results we have achieved in mice will translate into a cure for human diabetes and we need to be cautious that we dont promise more than we can deliver; but seeing what the hope of a cure does for these people is a reminder of what we are working for Vision: What role does philanthropy play in ensuring the progress of your efforts against diabetes? Dr Faustman: My research is where it is today thanks to philanthropic support The Iacocca Foundation established by former Chrysler Motors president Lee Iacocca in memory of his
wife, Mary, who died from type I diabetes; the foundation has pledged to raise 11 million to fund clinical trials through 2008 has been an instrumental source of support They
that characterizes the collaborative mindset at the MGH Dr Nathan: The MGH offers an extraordinarily supportive environment with world-class scientists scientists with whom clinical investigators can work closely to develop and test new therapies In this environment, bench-to-bedside translations occur on a regular basis and sometimes, with perseverance, ingenuity and a
The MGH offers an extraordinarily supportive
environment with world-class scientists scientists with whom clinical investigators can work closely to develop and test new therapies
– Dr Nathan
little bit of luck, important advances in clinical medicine take place The MGH research infrastructure allows for tremendous creativity and promotes these interactions Vision: How have the diabetes patients youve encountered affected your research, and vice versa? Dr Nathan: I still treat about 400 patients, in addition to my research and teaching activities, and the differences and hope I have seen in our patients over time have been quite
remarkable When I first started practicing endocrinology, too many increasingly to the epidemic of type 2 diabetes and its consequences Our research and clinical programs focus on improving the health of people with pre-diabetes, diabetes and its early complications and on caring for patients with more advanced medical complications Fortunately, we and others have identified the risk factors that need to be controlled in order to promote better health in patients at risk for diabetes, as well as the patients who already have developed it I wish I could guarantee that no one will develop diabetes or its complications in the future, but I can say that we have developed the means of reducing the otherwise devastating burdens of diabetes, and can keep patients healthier for longer durations
supported the basic science of this work, even when there was no guaranteed data, all because of a shared mission to cure diabetes Foundations and individuals need to support research than can take risks and find solutions to difficult problems Donors can make a tremendous impact in this regard The difference in starting a novel experiment, or delaying it, or not even doing it at all, is often
related to the generosity of an individual Donors can make all the difference in determining the timeframe of important discoveries Dr Nathan: The level of support received from the government has increased dramatically in recent years, and although we are grateful for that, funding still falls far short of the enormous need Recent cuts in NIH funding threaten the continuation of programs that have been started, and help is needed across the board In particular, the small pilot trials that test a unique hypothesis, and sometimes provide the basis for larger, definitive studies, are very difficult to fund with conventional federal sources The innovative clinical research performed at the MGH often starting with basic research, and followed by observational studies and finally clinical trials relies on the generous support of benefactors Committed donors turn scientific opportunities into research realities, and help advance the quest to improve the lives of people with diabetes For more information about the MGHs fight against diabetes, please visit http://wwwmassgeneralorg/diabetes/
Dr David Nathan
