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  • 1. Summer/Fall 2005 LEADING THE WAY TO A CURE FOR DIABETES INSIDE: • Helping children manage diabetes • Uncovering factors affecting fetal growth • Learning about metabolic syndrome • Hot Topics/Research Updates • Using gene therapy to combat CVD
  • 2. Message from the American Diabetes Association Research Grant Review Panel Chair With the number of Americans affected by diabetes rising each year, the American Diabetes Association’s commitment to funding quality diabetes research has never been more important. More than 18 million Americans have diabetes, but unfortunately nearly one-third of those people do not know it. I, along with the ADA, feel that clinical research, research directly involving patients, is critical to halting the spread of diabetes across our nation and to providing better care to those who already have the disease. The National Institutes of Health (NIH) also recognizes the importance of taking research results from the laboratory and quickly and safely moving them to human trials. The NIH Roadmap to Success stresses the need for “translational” research—research that focuses on taking discoveries learned in the laboratory to real-world use in patients. It is during this crucial step when discoveries are taken from “bench to bedside” that real progress can be made in fighting disease. Over the past year, the ADA has made significant changes to its research program that demonstrates its dedication to funding clinical research. The creation of the Distinguished Clinical Scientist Award emphasizes the Association’s commitment to clinical research by providing funds to outstanding researchers and thought leaders who have advanced the field of patient-oriented diabetes research. This award provides funding for established investigators who have made novel or watershed contributions to clinical diabetes research and who will continue to provide leadership in their research areas. The Association’s Clinical Research Award has become more focused on funding smaller studies whose purpose is to prepare for a larger investigation, as well as funding sub-studies which are part of larger, existing studies funded by government organizations such as the NIH. I believe this is an important change that will lead to these grants having better outcomes and more specific results in the three-year timeframe in which the research is carried out. Health services research and behavioral research which help answer questions about healthcare delivery, health education and how to improve services for patients with diabetes are now a major focus of the Clinical Research Award. This issue of Forefront provides an opportunity to learn more about some of the brightest minds and most interesting work being done in the field of diabetes research. Both clinical and laboratory-based research studies are featured, and both kinds of research are important to finding a cure and providing better treatments for people with diabetes. Back by popular demand, we have again included a “Hot Topics” section and “Research Updates” section, which highlight some of the latest and most innovative research into diabetes care and illustrate some of the many successes of ADA-funded research. I hope you find this issue of Forefront to be educational as well as inspiring. Sincerely, Timothy J. Lyons, MD 1
  • 3. Table of Contents Message from the ADA Research Grant LEADING THE WAY TO A CURE FOR DIABETES Review Panel Chair, Timothy J. Lyons, MD 1 I RESEARCH Type 1 Andrew Muir, MD Clinical Research Award Computer-assisted training (CAT) in self-management education of children with newly diagnosed type 1 diabetes and their families 3 I RESEARCH Type 2 Robert R. Henry, MD Mentor-Based Minority Postdoctoral Fellowship The effects of pioglitazone on lipid and glucose metabolism and cardiovascular risk factors in subjects with the metabolic syndrome 7 I RESEARCH Complications Helen Vlassara, MD Research Award Artistic rendering of the recruitment Treatment of diabetic atherosclerosis by of the adapter protein APS to the insulin receptor, a potentially gene therapy 11 important molecular event for insulin-stimulated glucose uptake I RESEARCH Targeted Patrick M. Catalano, MD into cells. This figure is based on Terry & Louise Gregg Diabetes in Pregnancy the three-dimensional structure Research Award reported in Hu et al., Mol. Cell Role of placental leptin in the 12, 1379-1389 (2003) regulation of fetal growth and adiposity 15 Photo submitted by Stevan Hubbard, PhD Hot Topics 19 New York University School of Medicine Research Updates 24 Co-editors: Message from the ADA Research Tory Asfahani Elizabeth Guzman Foundation Chair, Mr. Don Wagner 34 Design: Nichols & Duncan, Inc. 2
  • 4. Helping Children Manage Type 1 Diabetes Andrew Muir, MD W orking many summers at a youth camp in my home town of Toronto, Canada provided an excellent opportunity for me to be part of a nurturing and caring community at a young age. I loved the great outdoors and enjoyed watching children develop an early appreciation for the earth’s beauty. It was also around this time that I became interested in pursuing a career in medicine. Naturally, I considered going into pediatrics. In my first year of medical school, I took an elective in genetic research. Although I was not consciously aware of it at the time, my interest in research was sparked by this elective. As I look back, © Scavone Photography I recall frequently skipping my lectures so I could work on experiments in the lab. (Don’t worry, I read the lecture notes and passed all my exams.) Pediatric endocrinology offered the opportunity to Occupation: Associate Professor of Pediatrics and Chief, help people with difficult and sometimes unusual Pediatric Endocrinology problems and is a specialty with a heavy research Medical College of Georgia emphasis. As a senior medical student and a Augusta, Georgia pediatrics resident, I was inspired by a tremendous mentor, Dr. Denis Daneman, a pediatric Professional Focus: Early diagnosis and prevention of type 1 endocrinologist at the Hospital for Sick Children diabetes; improving access for individuals with diabetes to in Toronto. high quality care; prevention of death from cerebral edema. By the time I finished my pediatrics training, I was Outside Interests: Spending time with my four children and golf certain I wanted to do research in diabetes because Research Funding: Clinical Research Award I found myself intrigued by the complexity of the Computer-assisted training (CAT) in self-management education of autoimmune response that causes the condition. children with newly diagnosed type 1 diabetes and their families Today, in addition to conducting research, I Amount Awarded: $300,000 continue to work with children in a nurturing and caring community—only now my specialty in pediatrics allows me to focus on a full range of 3
  • 5. RESEARCH Type 1 I “...the number of children with diabetes is growing at with newly diagnosed type 1 diabetes and their families, is taking place at the Medical College of Georgia and the University of Florida over a three- also proposed. If it proves effective, CAT could rapidly be made widely available. year period. In this investigation, one half of the This project will also compare the cost and a rate much faster than the eighty participating families will complete a effectiveness of traditional diabetes education Web-based computer-assisted training (CAT) to the cost and effectiveness of a new computer- supply of pediatric diabetes course that will supplement three face-to-face assisted model of education. Families of children education specialists... ” visits with the diabetes team. The other half will complete diabetes education in eight traditional with newly diagnosed type 1 diabetes will receive factual information about diabetes using health issues concerning children with type 1 face-to-face sessions with the diabetes team. animated modules that are posted on the Web. diabetes while working alongside other dedicated Completion of these modules will reduce the professionals who all want to empower children We will examine costs to the providers and to the number of in-person visits with a diabetes with type 1 diabetes and their families to achieve families to treat diabetes over the first year and use educator required to become competent in and maintain healthier lifestyles. validated surveys to measure the outcomes of the diabetes care. Patients and their caregivers will be two education programs. The outcomes will include able to complete their education using a schedule While I love being a physician who has been diabetes knowledge and problem solving skills, that is suitable to their needs at a place more involved with diabetes research for 16 years and psychological and social adjustment to life with convenient than the clinic or doctor’s office and, could not imagine doing anything else, I recently diabetes, and satisfaction with the care provided obviously, miss less work or school to complete noticed a disturbing trend throughout the diabetes by the diabetes team. their initial diabetes education. community. Because young children cannot usually This program will also determine whether Simply put, the number of children with diabetes cope with the pace of traditional diabetes diabetes educators can offer patients better is growing at a rate much faster than the supply of education, development of a new CAT service by shifting some of their current teaching pediatric diabetes education specialists to care for program for children in grades 1-3 is responsibilities to computers. This should them. We therefore need new models to improve the efficiency of our care without reducing the effectiveness of our current interventions. Because the American Diabetes Association has a long history of focusing on patients and projects that will translate quickly to clinical practice, I turned to the Association to seek the funding that would support our investigation of a new computer- based education program designed to help families with a child newly diagnosed with type 1 diabetes. Our ADA funded grant, Computer-assisted training (CAT) in self-management education of children 4
  • 6. allow educators more time to effectively solve help a large number of people with diabetes. And As an investigator, I take the investment and trust the individual’s unique problems while analyzing here lies the beauty of our work—the far that is placed in me very seriously and feel blood glucose results from both new and reaching implications. privileged to have been funded by the ADA for a established patients. project related at least initially to type 1 diabetes. The American Diabetes Association is also far By the end of the trial, we expect to learn a reaching in its scope and plays a vital role in Type 1 diabetes research is headed steadily towards lot about who can benefit from independent the daily lives of people with diabetes. No other a cure and I hope to be a part of the team that finds learning methods and when they are best applied. organization is as active in communities in the the cure for type 1 diabetes. Improved diagnosis of Hopefully, we will also establish that the cost dissemination of information to individuals with islet autoimmunity will open non-toxic avenues of of providing diabetes education can be reduced diabetes, health care providers, legislators, etc. intervention that can be instituted before beta-cell by using new technology. As professionals, we rely on the ADA to establish loss reaches a clinically important stage and and maintain professional standards through its transplantation of cadaveric islets should give way Computer-assisted education is unique among my annual Clinical Practice Recommendations, to implantation of genetically modified self-cells, diabetes research efforts because it has immediate disseminate new research through its journals stem cells, and man-made devices. applicability to patients. My colleagues and I hope and annual Scientific Sessions, and help our that we will provide a means for allowing patients patients learn about their disease through books, I also foresee a new emphasis among pediatricians to receive the personal care they need and deserve local events, and so much more. on the prevention of obesity and more aggressive in a healthcare system that increasingly restricts treatment of risk factors for cardiovascular disease. “Association has a long opportunities for personal interaction between Over the next decade, I believe education about ...the American Diabetes healthy lifestyle and diabetes will become more providers and patients. important for children than it ever has been before. If our hypothesis is supported by the trial results, it will be much easier to convince physicians and history of focusing on The professional paths of all diabetes investigators third party payers that computer-assisted training are all headed to the same place—cure—but we of people with diabetes is a viable option to repeated patients and projects that are taking different routes to get there. For today, in-person visits. will translate quickly to I am tremendously exhilarated to work hard in contributing smaller pieces to the big puzzle while As a professor, I am obliged to explore novel methods of improving the lives of patients and clinical practice... ” providing every person with type 1 diabetes the information, skills, equipment, and motivation families with diabetes. As a physician, my aim is To the donor who has graciously given of his or her they need to tackle their disease. to provide the highest level of service and clinical resources to make the ADA the world class leader that quality while giving patients and their families the it is, I must say that ‘thank you’ is not enough. As for tomorrow, and with your ongoing support, best information and advice they need to make Irrespective of your contribution amount, my there is no doubt that we will see many more informed decisions about managing their illnesses. experience is that the motivation of ADA donors exciting, far reaching discoveries in diabetes With this particular ADA-funded project, however, is as true as one can find. For whatever reason that research. ■ the expected outcomes and benefits will extend you have been moved, you have made a pledge to beyond a finite group of individuals to ultimately make life better for someone who has diabetes. 5
  • 7. Preventing and Reversing Type 1 Diabetes at the Medical College of Georgia Scientists at the Medical College of Georgia have been SUMO4 is one of the zeroing in on the genetic causes of type 1 diabetes. key genes contributing to type 1 diabetes. Jin-Xiong She, PhD, joined the Medical College of But that isn’t all. They Georgia in 2002 as Professor and Eminent Scholar also discovered how in Genomic Medicine and Director of the college’s the gene is involved in Center for Biotechnology and Genomic Medicine. the development of Prior to coming to Georgia, Dr. She was the Director of diabetes. Thanks to Research for the University of Florida Diabetes Center their efforts, researchers and the Diabetes & Digestive & Kidney Diseases Cong-Yi Wang, MD now know that SUMO4 Biotechnology Center. While there, his research team, controls the activity of including Mark Atkinson, PhD, the American Diabetes the molecule NF B, which in turn controls the actions McCabe Association’s 2005 Outstanding Scientific Achievement Award winner, Andrew Muir, MD and Desmond Schatz, PhD, developed a prospective study of newborns of proteins called cytokines which regulate immune system responses. Dr. Wang found that when a mutation in the SUMO4 gene occurs along with an Glossary in the state of Florida. The study, Prospective environmental trigger, such as a viral infection, cytokine Assessment in Newborns for Diabetes Autoimmunity production increases and these cytokines direct the (PANDA), is designed to identify newborns with genes body’s immune system to attack the insulin-producing that put them at high risk for type 1 diabetes. PANDA beta cells of the pancreas. is funded by the National Institute of Diabetes & Digestive & Kidney Diseases of the National Institutes Dr. Wang continues his study of the genetic causes of Health. While researchers continue to study infants of type 1 diabetes through his ADA Junior Faculty in Florida, Dr. She has expanded the study to now Award, Role of TAB2 and SUMO4 in type 1 diabetes include newborns in the state of Georgia. The PANDA pathogenesis. It is believed that multiple genes are study will not only help identify newborns at risk for involved in the development of type 1 diabetes, and type 1 diabetes, but will also allow researchers to the purpose of Dr. Wang’s ADA grant is to not only understand more about when the disease process further study SUMO4, but also determine the role of starts. Insights into how the disease process begins a gene known as TAB2 in the progression of type 1 may also help scientists figure out how to prevent the diabetes. Dr. Wang will also verify whether environmental disease from developing. triggers play a role in the expression of this gene as they do for SUMO4. Learning more about TAB2 and Not long after his arrival at the Medical College of SUMO4 will help researchers to identify children at risk Georgia, Dr. She and his former postdoctoral fellow, for type 1 diabetes. Dr. Wang also hopes that his Cong-Yi Wang, MD, published a major type 1 diabetes study will be able to determine whether these genes finding in the journal, Nature Genetics (August 2004). can be targeted for therapeutic interventions to prevent Drs. She and Wang announced that a gene known as or cure the disease. ■ 66
  • 8. Metabolic Syndrome: A Risk Factor for Type 2 Diabetes Robert R. Henry, MD S uccess in life as well as in science requires creating promising possibilities. As a young child born and raised in Winnipeg, Manitoba, Canada I did not have the clear cut aspiration to become a doctor nor medical researcher. Yet, I always knew that by following my interests in the areas that were most stimulating to me, I would end up doing what I love most in life. Genuine intellectual curiosity, coupled with the fact that I always wanted to help people, led me to become a medical doctor. However, when I went into medicine, I quickly knew that I needed more than being a practitioner. Once involved in medical research, the discovery of new findings, no © Scavone Photography matter how small, was intriguing and made me want to know more about living things and how they developed. By gathering more information and expertise, wonderful opportunities soon Occupation: Professor of Medicine, University of California, San Diego unfolded that eventually led me to the rewarding Chief, Section of Endocrinology and Metabolism and challenging area of endocrinology research. Director, Center for Metabolic Research San Diego VA Healthcare System, San Diego, California My interest in endocrinology and, in particular, diabetes began in earnest while I was an intern Professional Focus: Adipocyte (fat)–skeletal muscle interactions and a resident in internal medicine. Following a including adipocyte secretory products and skeletal muscle insulin serious auto accident that landed me in the action/resistance; which factors regulate adipocyte secretory hospital for nearly a year, and while still on products (adipokines) and how they influence insulin action in crutches, I was offered the opportunity to be a skeletal muscle. fellow in diabetes and endocrinology. Outside Interests: Spending time with family, sailing, hiking. Even then, almost 30 years ago, it seemed Research Funding: Mentor-Based Minority Postdoctoral Fellowship obvious that the prevalence of diabetes would The effects of pioglitazone on lipid and glucose metabolism and increase dramatically in succeeding decades. cardiovascular risk factors in subjects with the metabolic syndrome I was also intrigued by the complexity of the Mentor-Based Postdoctoral Fellowship disease and the multiple system involvement for Translational research of insulin resistance, obesity, and type 2 diabetes the diabetic patient. Amount Awarded: $205,000 X 7
  • 9. RESEARCH Type 2 I “The ADA gavetome my first opportunity develop cholesterol blood level of less than 40 mg/dL (for men) or 50 mg/dL (for women); • Blood pressure of 130/85 mm Hg or higher, or understand how fat worsens the diabetic state, makes it more difficult to control glucose levels and how it contributes to increased vascular into a scientific researcher the need to use blood pressure medication; and, disease. If we don’t curb the adverse effects of fat, • Fasting blood glucose level of 110 mg/dL or an ever increasing number of Americans will and I continue to feel part higher. develop diabetes and its dangerous complications. of their team. ” Most people with metabolic syndrome also have insulin resistance meaning that cells in Besides disorders of glucose metabolism, the metabolic syndrome also involves altered free fatty This was also a time when the basic causes of the body resist the action of insulin, the hormone acid (FFA) metabolism, which could itself diabetes were being elucidated and there was that enables glucose to enter cells from the contribute to insulin resistance. Free fatty acids immense opportunity for scientific growth and bloodstream. The pancreas increases insulin are by-products of fat metabolism occurring in fat understanding. Cell biology, immunology and production to compensate for the resistance, but tissue. Our project is designed to determine if molecular biology were coming of age and the with time, this effort may fail. Blood glucose impaired FFA metabolism in the metabolic opportunity to translate this to diabetes was levels rise, eventually leading to type 2 diabetes. syndrome can be reversed by treatment with the unlimited. anti-diabetic drug, pioglitazone (Actos), and if During my fellowship, it became clear to me While we know that genetic (heredity) factors, such improvement would also impact the insulin that I wanted to pursue a career in diabetes severe overweight (obesity), an inactive lifestyle, resistance acquired from acute elevations in research, because the spark that started when I poor diet, a smoking habit, and older age all circulating FFA levels. was an intern and resident soon became a flame! contribute to insulin resistance and to metabolic syndrome, we don’t understand exactly what Determinations will be made of the effect of drug I just found the disease and its complications to causes insulin resistance. treatment on both the balance between glucose be fascinating. Today, my burning desire is to metabolism and FFA metabolism in the whole learn more about the metabolic syndrome. This is why I sought American Diabetes body, and pathways of glucose and FFA Metabolic syndrome is the term used for several Association funding for one of my current research metabolism in adipose tissue and skeletal muscle. specific physical problems that occur at the same projects, The effects of pioglitazone on lipid and Studies in isolated tissues or cells will allow time and increase a person’s risk for type 2 glucose metabolism and cardiovascular risk identification of the specific molecular sites of diabetes, heart attack, stroke, and premature factors in subjects with the metabolic syndrome. defects in metabolism and insulin resistance death. Nearly 25% of American adults have This investigation explores how fat—too much in metabolic syndrome. The diagnosis is made if all the wrong places—accelerates the a person has at least three of the following development of diabetes and, in particular, how fat characteristics: induces insulin resistance and an increased risk of • A waist larger than 40 inches (for men) or cardiovascular disease. Obesity and the 35 inches (for women); development of the metabolic syndrome is • Triglyceride (a type of fat) level of 150 milli- epidemic in the U.S. It is, in fact, present in a grams per deciliter (mg/dL) of blood or higher; majority of people with type 2 diabetes as well as a • High-density lipoprotein (HDL, or “good”) substantial number of type 1 patients. We need to 8
  • 10. and help determine if the effects of pioglitazone further exploration. The ADA gave me my first on metabolism and insulin action are due solely opportunity to develop into a scientific researcher to reductions in FFA levels or if other mechanisms and I continue to feel part of their team. Over the are involved. The effects of treatment on past 20 years, I have received many types of cardiovascular risk factors will also be followed research awards from the ADA and, currently, I to see if a favorable profile (protective against have two mentor-based fellowship awards (see cardiovascular disease) can be established. that it is not easy to get people to understand the “Young Scientist in Training – Brian Escala value and promise of research to future care and Chavez, MD” on page 10). This study should provide basic information about ultimate prevention. mechanisms of metabolic control and help identify These awards allow me to attract young targets for treatment for both preventing the Without research, we would not have new investigators with substantial promise who, with negative consequences of the metabolic syndrome discoveries and this can cause so many within the my guidance and direction, will hopefully lead the and reducing the progression to type 2 diabetes. diabetes community to become discouraged and next generation of diabetes discovery. Obviously, thus lose interest. By finding new ways to fight the ADA has not only been a strong and consistent Lifestyle changes are the first step in treating diabetes, everyone is encouraged to work harder supporter of my personal research efforts but it metabolic syndrome. Topping the list for insulin because it is research that makes these also contributes in major ways to the training of resistance is weight loss through increased improvements in treatments possible. new clinician-scientists. physical activity and a lower intake of calories. Best results have been achieved among those who And this is why the work of the American Diabetes To the readers of Forefront whose generosity funds lose seven percent to 15 percent of their baseline Association is so important. the ADA Nationwide Research Program, I would weight. Increasing the intake of fiber (found in say that you have contributed to a noble and vegetables, whole grains, and fruits) helps lessen Not only is the ADA dedicated to improving the worthwhile cause—one that uses your insulin resistance as does quitting smoking. lives of people with diabetes and to discovering a contributions wisely for the betterment of those cure, it also focuses a large part of its efforts on with diabetes and those at greatest risk. I assure To date, probably the most rewarding experiences research and funding investigators in all areas you that it is money well spent, earmarked for the as a medical doctor and researcher have been of diabetes. It has also funded many important most worthy of research projects with the highest sharing in my patients’ and their loved ones discoveries in recent times. likelihood of generating impactful discoveries. euphoria and gratitude when they achieve a happier human existence through better health. Moreover, at the core of the ADA are the volunteer Because of rapid advances in science, today more To help in making ill patients feel better is really and donor who assure that the organization is lean than ever we have an opportunity to take new quite satisfying. and highly effective. I have been thoroughly advances and translate them into tangible benefits impressed with the overall organizational structure for people with diabetes. Such progress could not On the other hand, the most difficult challenge we and the dedication of all the staff. The ADA’s have happened without you and can only continue sometimes face as care providers is dealing with the mission is clear and effective, but requires the with your ongoing generosity. Like you, I am also devastating complications after diabetes takes its toll consistent involvement of its volunteer constituents. a proud Pinnacle Society member and plan to —despite the best efforts of the patient and mine. keep on supporting the ADA in every way possible It is indeed an honor and privilege to receive and, with great enthusiasm, work toward and look Medical researchers like me also experience ADA funding and is indicative that my personal forward to a world without diabetes. ■ another difficult challenge. We find, at times, research interests are worthy of funding and 9
  • 11. The ADA Research Foundation thanks Takeda Pharmaceuticals North America, Inc. (TPNA) for supporting the Mentor-Based Minority Postdoctoral Fellowship Program. Dr. Brian Escala Chavez is a 2004 recipient of the ADA-TPNA Mentor-based Minority Postdoctoral Fellowship Award. Brian Escala Chavez, MD Young Scientist in Training—Brian Escala Chavez, MD Brian Chavez received his Bachelor’s degree in “I remember how appreciative many people were after bioengineering from the University of California, San what seemed to be ‘simple’ advice, such as explaining Diego, and his MD from the Medical College of what each medication they were taking was for and why Wisconsin in Milwaukee. After earning his medical insulin doses needed to be adjusted.” degree, Dr. Chavez returned to San Diego for his internship and residency, and is now completing his Asked about his reasons for wanting to help people with postdoctoral work under the guidance of Dr. Robert diabetes, Dr. Chavez responded that he has many family Henry through an American Diabetes Association members and friends affected by diabetes, including his Mentor-Based Minority Postdoctoral Fellowship Award. grandmother who passed away from cardiovascular complications of diabetes. “In the future,” Dr. Chavez During his college years, Dr. Chavez worked in the area states, “I plan to continue caring for patients with the of biomedical engineering, developing glucose sensors metabolic syndrome and type 2 diabetes in clinical for people with diabetes. While this was an interesting practice, and hope to continue my involvement in area of research, Dr. Chavez admits, “I realized I wanted clinical trials and research.” to work with people rather than be ‘behind the scenes’ and thus went to medical school and trained in internal Encouraging Young Minorities in Research medicine, then pursued a fellowship in endocrinology.” His research collaboration with Dr. Henry to study the The American Diabetes Association Mentor-Based drug pioglitazone (Actos) and its effects on fatty acids Minority Postdoctoral Fellowship Award was first offered and glucose is helping Dr. Chavez achieve his dream of in 2002. The Association recognized a noticeable gap working with patients and helping them to have a better in the number of minorities in the research arena, including quality of life. Dr. Chavez explains, “We are now diabetes research, and the minority postdoctoral fellowship recognizing what an epidemic obesity, the metabolic award was developed to address this important issue. By syndrome, and diabetes are becoming in modern creating a training opportunity specifically for young society.” By studying pioglitazone, an “insulin sensitizing” minority scientists, the Association felt it could help drug, and its mechanisms of action in people with the encourage minorities who are under-represented in metabolic syndrome, this research will provide insight clinical and basic science research to pursue a research into the prediabetic state and help scientists to develop career in diabetes. The Association mirrors the National new ways of preventing diabetes before it occurs. Institutes of Health guidelines in its definition of under-represented minority to include African American, His desire to help people can also be seen in his past Hispanic/Latino and American Indian/Alaskan Native record of volunteer work at clinics caring for low-income individuals. The Association has funded 16 minority patients. Dr. Chavez even states that the most satisfying postdoctoral fellowship awards since the program’s part of his diabetes research experience has been inception, and is looking forward to seeing the program volunteering to educate patients about diabetes. “I recall grow as more mentors and young minority scientists volunteering at a local non-profit conference where we take advantage of this opportunity. ■ were able to spend some time with people during an informal question and answer forum,” Dr. Chavez states. 10
  • 12. Using Gene Therapy to Combat Cardiovascular Disease in Diabetes Helen Vlassara, MD B orn and raised in beautiful Athens, Greece provided stimulating surroundings and, of course, a most historical and inspiring landscape for my early intellectual curiosity. I was also exposed to my father’s illness at a young age at which time a strong desire was born in me to alleviate the sense of helplessness that accompanies this experience. This, plus a deep curiosity about how the body works and how disease evolves, made me want to become a physician as well as a medical researcher. When I arrived at the Rockefeller University in New York more than 25 years ago to begin my post-doctoral training in medical research, I found myself surrounded by a © Scavone Photography group of brilliant scientists that was just about to discover a new type of hemoglobin modified by glucose. This molecule was named glycosylated hemoglobin A1c and was soon established as a highly reliable Occupation: Professor of Geriatrics, Medicine, Molecular Medicine indicator of the average blood glucose Director of the Division of Experimental Diabetes and Aging levels of diabetic patients over a period of Mount Sinai School of Medicine several weeks. New York, New York The enormous importance of the discovery Professional Focus: Understanding diabetes complications and of A1c soon became apparent and its investigating ways to curtail them. revolutionary impact on the traditional treatment of diabetes was about to unfold Outside Interests: Spending time with family and friends, literature, nationally and worldwide. This was a most competitive dancing, piano, drawing. exciting time in the field of diabetes and I Research Funding: Research Award found myself captivated by the dramatic Treatment of diabetic atherosclerosis by gene therapy benefit that a discovery like this provided in the long-term well being of all individuals Amount Awarded: $300,000 with diabetes. 11
  • 13. I RESEARCH Complications pressure and cholesterol, which increase (sugar-fat) complexes called advanced their risk for cardiovascular disease or glycation end products or AGEs. These are stroke. When combined with diabetes, shown to accumulate in cells, tissues and these risk factors add up to far greater organs and cause gradual malfunction trouble. In fact, more than 65 percent of and failure through chronic oxidant stress people with diabetes die from heart disease and inflammation. Although several Today, the clinical testing of A1c is of or stroke. With diabetes, heart attacks experimental drugs have been identified that paramount importance in assessing the occur earlier in life and up to four times can prevent this process, none have come severity of diabetes and adjusting the treatment more frequently. By managing diabetes well, along far enough yet to make it to clinic. of each patient with far greater accuracy. this risk can be reduced but not eliminated. Diabetic vascular disease continues to be In my nearly 30-year career in diabetes as a While there has been tremendous progress a major cause of death today. (For more scientist, I have always depended on the ADA toward improving the management of diabetes, information on the link between diabetes and for its tremendous efforts in promoting particularly over the last 10 years, prolonged cardiovascular disease, visit ADA’s Web site at knowledge and research. Recently, I appealed hyperglycemia still occurs. However mild, it www.diabetes.org/diabetes-heart-disease-stroke.) to the Association once again for the funding still leads to severe vascular, renal and of a novel research project designed to help neurological complications. Moreover, the individuals with diabetes who are facing incidence of type 2 diabetes continues to rise among adults (due to excessive eating and “...individuals with diabetes are more likely perhaps one of the disease’s worst complications—diabetic vascular disease. lack of exercise) or older people (due to extended longevity), but also among much to develop far more This ADA-funded project, Treatment of younger persons. This is extremely alarming diabetic atherosclerosis by gene therapy, and a much greater effort must be mounted serious cardiovascular focuses on an extremely powerful and toward understanding and reversing the promising approach—gene transfer—that dismal demographics of the disease itself. and renal disease than may bring forth a novel therapeutic At the same time, until a definitive cure for diabetes becomes available, the treatment of are non-diabetics. ” intervention for the prevention of the vascular disease that affects the well-being of most individuals with diabetes. its complications, especially vascular and The majority of my work has focused on the kidney disease, is a top priority for the prevention and reversal of the cardiovascular We have identified a natural protein called future of diabetes-related research because and renal complications brought about by lysozyme which is present in the body, individuals with diabetes are more likely to chronic diabetes, whether type 1 or type 2. It normally helping to fight infections. This develop far more serious cardiovascular and is a well known fact that high levels of certain protein can also capture toxic AGE, helping in renal disease than are non-diabetics. sugars, like glucose in diabetes, provoke a their disposal from the body through the complicated series of chemical reactions (an kidneys. We now plan to investigate the Most adult individuals develop health early product of which is A1c) which result in potential of lysozyme as a new therapy problems over the years, such as high blood a large number of sugar-protein or sugar-lipid against diabetic complications. Using animal 12
  • 14. Chair of the Research Grant Review Panel, Chair of the Council on Complications, organizer of symposia, and as a member of the Editorial Board of the journal, Diabetes. models of type 1 and type 2 diabetes, and favorably change these odds in a meaningful I deeply believe in the importance of the crossing them with genetically manipulated way. Every day, the need for diabetes research service that the ADA provides to all health mice that carry large amounts of the becomes increasingly more important professionals, individuals with diabetes and lysozyme gene, we have observed that high because the general public’s awareness their families. The ADA is an indispensable levels of this protein appear to offer protection and education regarding diabetes and its organization that has embraced all aspects from vascular and renal damage, despite the dangerous complications are not keeping up and needs of the diabetes community— presence of diabetes. This protein appears to with the prevalence of the disease. education, medical care and, of course, be unique in that it not only helps with the research. It has supported my research ever removal of AGE from the body, but it also Indeed, the most critical and time-resistant since I was a junior researcher and this has counteracts the tendency of AGE to cause difficulties I have encountered throughout continued to the present, long after I became excessive oxidation, inflammation and my career have always been the low levels an established senior investigator. Fortunately eventual damage of tissues and organs. For of public awareness or education related to for so many of us in the research community, example, diabetic animals which typically diabetes and the persistently low priority the ADA has always appreciated the have high glucose and lipid levels, and given to this disease by the general importance of novel ideas and breakthroughs consequently develop severe vascular disease medical/scientific and federal agencies. Even and, in doing so, fulfills the role of a unique (atherosclerosis), are significantly protected today, despite the huge efforts made to alert organization set to utilize every potential that from this serious problem if they carry high the general population about the “epidemic years of experience in this field can offer. levels of the lysozyme gene. proportions” of diabetes, there is an overall frustrating denial toward this disease and the I can only express admiration and respect for Based on these exciting findings, we plan to urgent need for effective strategies in terms of the commitment and dedication that the introduce the lysozyme gene into diabetic educational tools developed for families and American Diabetes Association displays in animals with the help of viral vectors. Viral schools, for the timely availability of new multiple ways that have enabled it to achieve so vectors are harmless viruses that can transport treatments made to physicians and other much over the years and I am confident that desired genes into an animal’s cells. We will health professionals, and in particular, for it will continue to be supported by the extremely use vectors similar to those that have been greater financial support of research. generous donors until the day the battle already used in the treatment of many other against diabetes and its complications is won. diseases in humans to evaluate the possibility There has to be a brighter outlook and this of this approach as a therapy for the long- is where the American Diabetes Association Thank you for your interest in diabetes research term complications of diabetes. comes in. and your gracious support of my life-long commitment to eliminate this disease or, in As a physician, I am constantly aware of the Throughout my career, I have been involved the meantime, to make the lives of those with odds faced by our patients with diabetes and with the ADA not only as a member and diabetes free of risk, healthier, longer and this is a reminder that only research can repeatedly funded researcher, but also as more livable. ■ 13
  • 15. Women in Research at Mount Sinai School of Medicine Rosalyn Yalow, PhD Dr. Helen Vlassara is in good company at Mount Sinai of the American Diabetes School of Medicine. She joins Rosalyn Yalow, PhD, who Association (sponsored by not only conquered social and professional barriers to Eli Lilly and Company) for her discovery and its become a leading female medical physicist, but became implications in the care of those with diabetes. only the second woman in history to receive the Nobel The American Diabetes Association presents the Prize in Physiology or Medicine in 1977. Outstanding Scientific Achievement Award each year to an individual researcher under age 45 who Rosalyn Yalow was born Rosalyn Sussman in the Bronx, has made an outstanding contribution to diabetes New York in 1921. Demonstrating an early aptitude for research that demonstrates both originality and math, she graduated from Hunter College in New York independence of thought. with a degree in physics, but because of a lack of interest in women scientists, was forced to take a job as a Despite the death of her colleague, Dr. Berson, in 1971, typist to a biochemist. However, in 1941, Dr. Yalow Dr. Rosalyn Yalow persevered in her work and went on unexpectedly received an assistantship from the to receive the Nobel Prize in Physiology or Medicine in University of Illinois and became the first woman at the 1977 for continued development of RIA in peptide school’s College of Engineering since 1917. While her hormones. RIA now has multiple medical applications, acceptance at the school was in part due to a shortage including screening blood for hepatitis virus, determining of men eligible to attend (most were being drafted into effective levels of drugs and antibiotics in the blood, the military), she proved herself a talented researcher. detecting foreign substances in the blood, and even Dr. Yalow received her PhD in nuclear physics in 1945, testing hormone levels in infertile couples. Dr. Yalow and then returned to New York where she became a is now retired. The Bronx VA Hospital where she consultant and later a faculty member at the Bronx performed her research is now affiliated with Mount Sinai Veterans Administration (VA) Hospital. Here she joined School of Medicine where Dr. Yalow holds the title of Dr. Solomon Berson in conducting research on medical Distinguished Service Professor. applications of radioactive materials. It was this work which would eventually lead Drs. Yalow and Berson to Dr. Yalow’s accomplishments include not only her develop a new technology known as radioimmunoassay professional work and awards received, but also her (RIA) to prove that the immune system could recognize determination to overcome the social and cultural and respond to small molecules, such as insulin, in the barriers faced by the women of her time. While she bloodstream. By binding animal insulin to radioactive found inspiration in the autobiography of Madame Marie iodine, Dr. Yalow was able to determine the rate of Curie, another Nobel Prize winner, young women are disappearance of insulin from the circulation of insulin- already finding inspiration and have begun honing their treated patients, and determined that the patients scientific talents thanks to Dr. Rosalyn Yalow. And it developed antibodies to the animal insulins. She and Dr. is thanks to the contributions of talented women Berson had, in effect, developed a tool for measuring researchers like Dr. Yalow and Dr. Vlassara at Mount insulin levels in the bloodstream. In 1961, Dr. Yalow Sinai School of Medicine that we will continue to make received the Outstanding Scientific Achievement Award progress in the fight against diabetes. ■ 14
  • 16. Diabetes in Pregnancy: Uncovering the Factors that Affect Fetal Growth Patrick M. Catalano, MD W e have all heard the worn out cliché reminding us that “two heads are better than one.” But maybe it is not as worn out as it sounds. Yes, there are countless researchers who do their best work alone and their ideas and accomplishments are appreciated. Most of us, however, are usually grateful for all the help we can get. In science, no researcher or idea stands alone. We continuously build on one another’s work, past and present. It is also especially important to form a supportive network and have contact with people who share similar research interests because there are times when research can be somewhat isolating. Partnering or interdisciplinary research not only helps to © Scavone Photography increase motivation and interest, but will also contribute to highly successful research that better qualifies for obtaining research grants. Such is the case with my current partnership Occupation: Professor of Reproductive Biology with Dr. Sylvie Hauguel-de Mouzon, a Chairman of the Department of Obstetrics and Gynecology collaborating investigator on my ADA-funded Case Western Reserve University at MetroHealth Medical Center project, Role of placental leptin in the Cleveland, Ohio regulation of fetal growth and adiposity. Professional Focus: Mechanisms related to the development of The Terry and Louise Gregg ADA funding was insulin resistance in pregnancy; fetal growth and body composition specifically granted for research in the area of diabetes and pregnancy, including placental Outside Interests: Jogging, squash, travel, and reading, especially leptin metabolism, which is a strength of history novels Dr. Hauguel-de Mouzon, and fetal overgrowth causing overly large babies, which is a joint Research Funding: Terry & Louise Gregg Diabetes in Pregnancy interest of ours. Research Award Role of placental leptin in the regulation of fetal growth and adiposity Based on our common interests related to Amount Awarded: $300,000 diabetes in pregnancy, as well as gestational diabetes, we plan to develop research methods that will lead to the prevention of fetal obesity 15
  • 17. RESEARCH Targeted I which we believe may have potential long Our research has shown that increased placentas of women without diabetes. term implications for both the children and amounts of fat tissue contribute to this This investigation will permit us to better mothers. excessive growth, which creates a greater risk define the role of leptin in pregnancy and of developing obesity and diabetes later in life. help us determine the factors that are The problem of obesity is epidemic, not only Our team has previously shown that the responsible for overgrowth and obesity of the in this country, but in the developing world. placenta controls fetal growth by producing fetus. Once we understand the processes While diabetes in pregnancy may represent hormones that modify fetal nutrition. The related to fetal overgrowth, we can then an interesting pattern in itself, our research is hormone leptin is produced in the adipose implement intervention measures to decrease leading us to believe that maternal obesity, tissue of the mother, the fetus and also in the the risk of fetal overgrowth and then hopefully through metabolic mechanisms, may affect placenta. When a fetus is obese, particularly long term complications such as obesity and fetal overgrowth which may in turn have in diabetic women, the placenta produces type 2 diabetes. Coupled with our clinical long term implications for the development more leptin. studies, this investigation will help us improve of diabetes and the metabolic syndrome (see the means by which basic research can be page 8) in children born to these mothers. translated into clinical care of our patients. Because of the increased insulin resistance, “...offspring ofadiabetic mothers have higher pregnancy demands more insulin in the body. An inability of the body to keep up with this risk of developing insulin demand can lead to diabetes during pregnancy. In addition, increased production diabetes and obesity ” of molecules by the the placenta increases insulin resistance, a diagnostic feature of later in life. common diabetes. Diabetes during pregnancy is a serious condition that endangers the In our ADA-funded project, we are health of the unborn fetus and the mother. investigating the molecular basis of the changes that occur in the placenta of diabetic Sylvie Hauguel-de Mouzon, PhD and While in the uterus, the development of the and obese women. Recently, we identified Patrick M. Catalano, MD fetus is totally dependent on the placenta. placental signals which are associated with The placenta is a unique and necessary an increase in fetal adipose tissue. The aim Dr. Hauguel-de Mouzon and I consider this to boundary between the mother and her fetus. of this project is also to learn how leptin be an important investigation, especially When a woman is or becomes diabetic during affects the growth of the fetus. We are given the fact that more than 10 years after pregnancy, the placenta receives all kinds currently studying factors that stimulate the the discovery of leptin’s role in pregnancy, it of signals and stimuli that may modify production of leptin by the placenta. Our continues to be poorly understood. This is placental function and, consequently, the studies compare lipids in the placentas of why we are so grateful for the ADA’s support growth of the fetus. diabetic mothers with lean and obese babies and consider receiving our award very in order to determine if their placentas important for two specific reasons. First, ADA One major complication of diabetic transport more lipids to their babies than funding helps us face the high cost of pregnancy is excessive growth of the fetus. 16
  • 18. research studies in molecular biology. Second, the funding is specifically used to improve our understanding of the placental function in a diabetic environment and its consequences for the developing fetus; thus, promoting diabetes research at the earliest stages of life. Support for our project also demonstrates the Association’s interest in addressing pregnancy disorders that may have long term consequences for infants, and the value in basically “nipping the problem in We are really quite proud to have been have both participated in multiple ADA the bud” for preventing what may turn out to awarded this grant by the ADA both as meetings and conferences and continue to be greater problems later in life. individual investigators and as a team be thoroughly impressed with the level of merging basic and clinical studies. We dedication our peers and colleagues To date, Dr. Hauguel-de Mouzon and I find sincerely hope that our unique approach demonstrate toward their research efforts. I that one of the most difficult challenges we combining studies on mothers, placentas and personally have been involved with the local face as researchers is to convince the scientific newborns will contribute to improving the ADA office in Cleveland as well as on a community that diabetes is a lifelong disease heath care outcome in diabetic pregnancy. national level and believe that the American which often starts before birth. For many If we can determine that obesity at birth is Diabetes Association has an excellent years, diabetes in pregnancy has gained little related to exposure to specific maternal combination of input from people in attention in regard to the importance of basic stimuli during pregnancy, then rational families living with diabetes as well as the research studies and funding. It is crucial to plans for primary prevention rather than commitment from the researchers aiming recognize that there is more to it than the treatment can be developed. to make life with diabetes more livable. clinical goals of providing the appropriate They are all to be commended. dose of insulin to diabetic pregnant women. And because the funding for our research project was largely due to the extraordinary We recognize that although investigators It has also become quite obvious that generosity of Mr. and Mrs. Terry and Louise occasionally make large strides, more offspring of diabetic mothers have a higher Gregg of Malibu, California, we would also commonly it is through small steps built on risk of developing diabetes and obesity later in like to thank them for their remarkable the work of others that we move forward in life. Researchers now believe that this may be support and recognize that this work would our research. Much like a baby’s first steps, the result of the adverse environment in not be taking place had it not been for their we all start out walking before we learn to which the fetus develops. This is known as heartfelt desire to help struggling mothers-to- run. In the long run, and thanks to the metabolic programming or fetal origin of be realize their dream of having healthy unfailing generosity of the American Diabetes adult diseases. Thus, the worldwide epidemic pregnancies and healthy babies. Association donors, I see us crossing the finish of obesity starting in adolescence and even line together, hand in hand, in our race earlier in childhood may have some Both Dr. Hauguel-de Mouzon and I have been toward the cure for diabetes. ■ components of prenatal origin. affiliated with the ADA for many years. We 17
  • 19. American Diabetes Association Support of Gestational Diabetes Research The ADA supports gestational diabetes (GDM) research C-peptide is in many ways. Through its core funding program and a subunit of support of government-run clinical trials, and by insulin created organizing and funding scientific meetings focusing on by the diabetes during pregnancy, the Association shows its pancreas, and is measured to determine the amount of commitment to caring for women and infants affected insulin being produced by the pancreas. Second, DNA by this disease. samples from both the mother and the infant will be stored and will become a resource for later studies in: The ADA provides co-support to federally-funded predisposition to type 2 diabetes, obesity, hypertension research programs which it feels hold significant promise and cardiovascular disease in women who have had to affect the lives of individuals with diabetes or those at gestational diabetes; fetal growth and long-term growth risk for developing the disease. The Hyperglycemia and and development, as well as risks of obesity and Adverse Pregnancy Outcome Study (HAPO) is one such diabetes, in their children. program. Funded primarily by the National Institute of Child Health and Human Development (NICHD) and the The ADA is also proud to sponsor the 5th International National Institute of Diabetes, Digestive & Kidney Workshop Conference on Gestational Diabetes Diseases (NIDDK), the HAPO study is led by Boyd scheduled for November 11-13, 2005 in Chicago, Metzger, MD at Northwestern University in Chicago, Illinois. The three-day program will bring together Illinois. The purpose of this study is to determine researchers from around the world to discuss the whether pregnant women with hyperglycemia have a disease processes involved in the development of GDM, higher risk of poor maternal, fetal and neonatal outcomes. management of GDM, and post-partum follow-up of both women and infants. The goal of the meeting is to Investigators from 16 clinical centers around the world encourage dialogue between researchers in an effort to are working together to examine glucose tolerance in a develop specific recommendations for further GDM multicultural, multinational and ethnically diverse group research. The NIDDK is also organizing a meeting of women in the third trimester of pregnancy. Their goal to be held in September 2005 on the long-term is to obtain information on the relationship between consequences of the intrauterine environment on the blood glucose levels in pregnant women and the risk of development of obesity and metabolic disease, with a certain adverse outcomes. This information will be used concentration on the effects of maternal obesity and to develop international criteria for the diagnosis of GDM. diabetes on children. These meetings are an example of the commitment of the scientific community to study Support from the American Diabetes Association has the effects of diabetes in pregnancy. enabled researchers to add two critical resources to the main HAPO study that will greatly add to the study’s By funding research and promoting collaboration among overall results. First, c-peptide levels will be obtained scientists, the ADA hopes to find improved ways of during the oral glucose tolerance tests performed on all treating, preventing and ultimately eliminating diabetes of the pregnant women participating in the study. during pregnancy. ■ 18
  • 20. Hot Topics T H E E X PA N D I N G P R O B L E M O F O B E S I T Y Why lose weight? Americans have been flooded with newspaper and Being overweight or obese and leading a sedentary magazine articles as well as television news stories lifestyle are some of the leading risk factors for about obesity and diabetes. By now many people are developing type 2 diabetes, and nine out of 10 people aware that there is an increasing incidence of obesity newly diagnosed with type 2 diabetes are overweight. in the U.S. The latest data from the National Center The body mass index (BMI) chart on the next page can for Health Statistics show that 30 percent of U.S. be used to determine whether a person is overweight adults 20 years of age and older—over 60 million or obese. Individuals who are overweight have a BMI of people—are obese. The prevalence of overweight 25.0-29.9, while those with a BMI greater than or equal among children and adolescents has also risen to 30 are considered obese. While the BMI chart is alarmingly over the past three decades. National used by many researchers and clinicians, there are Health and Nutrition Examination Survey (NHANES) some who feel it does not accurately predict the data over the past 30 years has indicated the likelihood of developing a disease since abdominal prevalence of overweight in 6-11 year-olds has almost obesity (fat deposited in the abdomen around the quadrupled and the prevalence in 12-19 year-olds organs) has been shown to be a better indicator of has increased 2.5 fold. The most recent 1999-2000 disease risk. Therefore, waist circumference has NHANES data estimates that 15 percent (almost nine become another useful indicator of obesity. Men million) children and adolescents ages 6-19 are with a waist circumference greater than 40 inches overweight. The 1999-2000 findings for children and and women with a waist circumference greater than adolescents suggest the likelihood of another 35 inches are considered obese and, as one recent generation of overweight adults who may be at study showed, are at greater risk for cardiovascular increased risk for obesity, as well as related disease. Unlike other diabetes risk factors like genetics cardiovascular disease and type 2 diabetes. or age, a person’s weight and activity level are two factors that may be possible to control. Because of that, we are seeing an increased research focus on obesity, diet and exercise. The recently completed Diabetes Prevention Program (DPP) was a major clinical trial funded by the National Institutes of Health, National Institute of Diabetes & Digestive & Kidney Diseases with support from the American Diabetes Association. The purpose of the study was to discover whether diet and exercise or the oral diabetes medication, metformin (Glucophage), could prevent or delay the onset of type 2 diabetes in people with impaired glucose tolerance (IGT). IGT, also called impaired fasting glucose (IFG) or “pre-diabetes,” is a condition in which blood glucose levels are higher 19
  • 21. Weight in Pounds 120 130 140 150 160 170 180 190 200 210 220 230 240 250 4'6" 29 31 34 36 39 41 43 46 48 51 53 56 58 60 4'8" 27 29 31 34 36 38 40 43 45 47 49 52 54 56 4'10" 25 27 29 31 34 36 38 40 42 44 46 48 50 52 5'0" 23 25 27 29 31 33 35 37 39 41 43 45 47 49 Height in Feet and Inches than normal (110- 5'2" 22 24 26 27 29 31 33 35 37 38 40 42 44 46 Heart, Lung and 125 mg/dL) but 5'4" 21 22 24 26 28 29 31 33 34 36 38 40 41 43 Blood Institute’s Third not high enough 5'6" 19 21 23 24 26 27 29 31 32 34 36 37 39 40 Report of the National for a diagnosis of Cholesterol Education 5'8" 18 20 21 23 24 26 27 29 30 32 34 35 37 38 diabetes (126 Program Expert mg/dL or higher). 5'10" 17 19 20 22 23 24 26 27 29 30 32 33 35 36 Panel on Detection, Results of the DPP 6'0" 16 18 19 20 22 23 24 26 27 28 30 31 33 34 Evaluation, and study showed that 6'2" 15 17 18 19 21 22 23 24 26 27 28 30 31 32 Treatment of High losing even a small 6'4" 15 16 17 18 20 21 22 23 24 26 27 28 29 30 Blood Cholesterol amount of weight in Adults (Adult 6'6" 14 15 16 17 19 20 21 22 23 24 25 27 28 29 (five to seven Treatment Panel III). percent of body 6'8" 13 14 15 17 18 19 20 21 22 23 24 25 26 28 Known as the ATP III weight) through criteria, this group Underweight Healthy Weight Overweight Obese diet and exercise defined metabolic can reduce the risk Note: This chart is for adults (> 20 years old) syndrome as having of developing any three of the diabetes by approximately 58 percent across all age following five symptoms: abdominal obesity determined and ethnic groups, and the results for older study by waist circumference, high triglycerides > 150 mg/dL, participants were even more striking with the risk of low HDL or “good” cholesterol (<40 mg/dL for men and diabetes reduced by 71 percent. Study participants <50 mg/dL for women), blood pressure > 130/85 who received metformin had a 31 percent reduced risk mmHg, and fasting blood glucose levels > 110 mg/dL. of developing diabetes, however metformin was shown While not everyone has adopted this definition, most to be most effective in younger individuals age 25–44 agree that the more symptoms a person has, the more years who were at least 60 pounds overweight. at risk they are for developing cardiovascular disease or other complications. Metabolic syndrome affects one Obesity can also contribute to a disorder called out of every five overweight people. the “metabolic syndrome.” Also known as “insulin resistance syndrome” or “syndrome X,” the metabolic Many people are able to lose weight by making syndrome is a combination of metabolic problems changes to their diet and increasing their amount of including obesity, high blood pressure and high exercise. Exercise not only promotes weight loss by cholesterol levels, which can lead to hardening of the burning excess fat and increasing muscle mass, but it arteries, cardiovascular disease and kidney disease. also improves the body’s response to insulin which can There is some controversy surrounding the precise make a big difference to people who are insulin definition of metabolic syndrome. While the American resistant. Reducing the number of calories eaten per Diabetes Association does not endorse one specific day and controlling portion sizes can also contribute definition, there are some organizations and clinicians to weight loss, which may help some people with that do use the criteria developed by the National diabetes reduce or eliminate their need for oral 20
  • 22. Hot Topics T H E E X PA N D I N G P R O B L E M O F O B E S I T Y diabetes medications. Many popular “fad” diets lack It is clear that overweight and obesity can cause health the support of quality research studies to prove problems. But the results of the DPP study show that whether they work. However, a recent clinical trial losing weight is possible and, more importantly, losing designed to study the effects of the Atkins diet was weight and exercising can help prevent or reverse those led by Guenther Boden, MD at Temple University in health problems. However, there are some situations Philadelphia, Pennsylvania. The study revealed that the in which diet and exercise are not effective at helping primary reason behind the weight loss on followers of people lose weight. So we ask ourselves, how is this diet plan was a reduction of calories. See the medical science addressing the issue of weight loss? article on page 28 for more details. Oral Medications to Treat Obesity There are several prescription drugs now available to treat obesity. Weight loss drugs are usually not recommended for those who are only mildly overweight unless there are other serious health problems such as diabetes or heart disease. A recent article in the April 5, 2005 issue of Annals of Internal Medicine reports on the results of a study to assess the safety and effectiveness of U.S. Food and Drug Administration (FDA) approved weight loss medications and other medications used for weight loss. Researchers reviewed 79 clinical trials involving dietary intervention plus the following obesity drugs: Generic name Brand name Method of action sibutramine Meridia appetite suppressant orlistat Xenical prevents absorption of fats phentermine Adipex-P, Fastin, Ionamin, Oby-Trim appetite suppressant diethylpropion Tenuate appetite suppressant fluoxetine Prozac primarily for depression; balances natural brain chemicals bupropion Wellbutrin primarily for depression and smoking cessation, balances natural brain chemicals topiramate Topamax primarily used to treat epilepsy sertraline Zoloft primarily for depression; balances natural brain chemicals zonisamide Zonegran primarily used to treat epilepsy 21
  • 23. Review of the drug trials showed that sibutramine, Do combinations of drugs promote greater orlistat, fluoxetine, sertraline, bupropion, topiramate weight loss than one drug alone, and are drug and zonisamide can cause modest weight reduction of combinations safe? approximately five kg (slightly more than 11 lbs) or less If more intense diet and exercise interventions are after one year of use when combined with dietary combined with weight loss medications, will intervention. This may not seem like very much, but individuals be able to lose even more weight than when one considers that the Diabetes Prevention current studies suggest? Program (DPP) trial showed a medical benefit with a mere five percent loss of body weight, weight loss How long should each drug be taken? One year? drugs may be very beneficial in helping obese Two years? Ten years? individuals reduce their risk of diabetes. The review Side effects of the drugs are also an important issue also revealed that among the drugs listed above, and should be thoroughly discussed between patient sibutramine and orlistat have been studied the most. and medical provider before making the decision to In fact, GlaxoSmithKline recently reported results of a begin drug therapy for obesity. Some of the side four-year study demonstrating that weight loss with effects of the drugs discussed here included increases orlistat can reduce the risk of developing type 2 in blood pressure and heart rate, gastrointestinal diabetes in individuals with impaired glucose tolerance. symptoms (diarrhea and flatulence) and effects on Research results published in April 2004 Diabetes Care the central nervous system. revealed that sibutramine significantly reduced body weight and waist circumference as well as fasting blood glucose and A1c levels in individuals treated with the drug. In addition to the drugs discussed above, the pharmaceutical company, Sanofi-Aventis, is in the process of developing a drug known as rimonabant (Acomplia), which is a new form of appetite suppressant that has been shown to be quite effective in weight loss. The company plans to file a new drug application for Acomplia with the FDA this year and, if successful, market the drug in 2006. Despite the research and availability of new drugs, there are still many questions left to be answered. The authors of the review paper suggest that the long-term effects of these drugs on health outcomes be studied to ensure long-term safety as well as effectiveness. Other questions raised included: 22
  • 24. Hot Topics T H E E X PA N D I N G P R O B L E M O F O B E S I T Y Surgery to Treat Obesity The first bariatric surgery was performed in 1954 and since then the number of weight loss surgeries has climbed along with the rate of obesity. According to a weight loss surgery review article published in the April 5, 2005 issue of Annals of Internal Medicine, an estimated 140,000 surgical procedures for weight loss were performed in the U.S. in 2004. The study, funded by the U.S. Agency for Healthcare Research and Quality, reviewed 147 clinical trials on the surgical treatment of obesity including procedures known as gastric bypass, laparoscopic adjustable gastric band technique, and biliopancreatic bypass, all of which serve to reduce the size of the stomach and re-route the intestines in order to prevent food from being absorbed and, as a result, promote weight loss. Results show that surgery can result in considerable weight loss (20-30 kg or approximately 44-66 lbs) for severely obese individuals with a BMI greater than or equal to 40, and one study reported continued weight loss over eight years with improvements in diabetes after surgery. Many obesity surgery studies have also shown improvements in hypertension, dyslipidemia (a fat protein metabolism disorder resulting in high levels of “bad” or LDL cholesterol and low levels of “good” HDL cholesterol), and sleep apnea following surgery. But more data are needed to determine the effectiveness and appropriateness of each different type of surgery for different types of individuals. Complications resulting from surgery occur in approximately 20 percent of people who undergo the procedures, and researchers must focus on ways to reduce these complications which can include internal bleeding or gastrointestinal problems such as vomiting or acid reflux. Finally, research should be done to determine if surgery is effective for less severely obese individuals. Clearly, more work needs to be done in the area of obesity research. What we do know is that excess fat, especially when located in the abdomen, contributes to diabetes and cardiovascular disease and that losing weight can help decrease one’s risk for these diseases. Whether diet and exercise, prescription weight loss medications, or surgery is the best method for weight loss depends on the individual’s level of overweight or obesity and their personal needs and doctor recommendation. We are fortunate that science has brought us to the point where medication and surgery are effective weight loss options, but we still await the day when researchers will find answers to crucial questions of long-term safety and effectiveness of each type of therapy among different groups of people affected by obesity. ■ 23
  • 25. Research UPdates ANNOUNCEMENTS Healthy Food Choices Awardees The prevalence of overweight among children and adolescents has risen alarmingly over the past three decades. National Health and Nutrition Examination Survey (NHANES) data over the past 30 years has indicated the prevalence of overweight in 6-11 year-olds has almost quadrupled and the prevalence in 12-19 year-olds has increased 2.5 fold. The most recent 1999-2000 NHANES data estimates that 15 percent (almost nine million) children and adolescents ages 6-19 are overweight. The 1999-2000 findings for children and adolescents suggest the likelihood of another generation of overweight adults who may be at increased risk for obesity, as well as related cardiovascular disease and type 2 diabetes. The purpose of the Healthy Food Choices Research Awards, funded by the ARAMARK Charitable Fund, is to support educational, behavioral, and nutritional outcome studies supporting a better understanding of healthy food choices in children and adolescents in order to prevent obesity. The American Diabetes Association is pleased to announce the award recipients of our newest targeted research opportunity, the Healthy Food Choices Research Award: Valerie Duffy, PhD, RD University of Connecticut Storrs, Connecticut The Captain 5 A Day Program: Improving dietary quality and physical activity in preschoolers Sylvie Naar-King, PhD Wayne State University Detroit, Michigan Adapting multisystemic therapy to improve food choices and health outcomes in obese African American youth Hollie Raynor, PhD, RD The Miriam Hospital Providence, Rhode Island Changing eating behaviors in young children: Should healthy foods be increased or unhealthy foods decreased? 24
  • 26. Research UPdates ANNOUNCEMENTS Type 1 Diabetes TrialNet The American Diabetes Association is a proud medications to prevent the destruction of beta cells in supporter of the federally-funded clinical trials of patients newly diagnosed with type 1 diabetes. TrialNet TrialNet. TrialNet is a network of 18 clinical centers in is funded by the National Institute of Diabetes & the United States, Canada, Europe, and Australia, Digestive & Kidney Diseases (NIDDK) through the Type working together to prevent or delay type 1 diabetes. 1 Diabetes Special Statutory Funding Program which TrialNet began thanks to a recommendation from the commits $1.14 billion for type 1 diabetes research from Diabetes Research Working Group (DRWG), which 1998-2008. This funding is an addition to the regularly formed as a result of the Surgeon General’s Report, appropriated funds received by the Department of Healthy People 2010. The goal of the DRWG was to Health and Human Services (HHS) for diabetes develop a strategic plan for diabetes research. One research. The National Institute of Child Health and recommendation of this group was to develop clinical Human Development (NICHD), the National Institute trials to prevent type 1 diabetes. of Allergy and Infectious Diseases (NIAID) and the American Diabetes Association are also sponsors of Two TrialNet studies are currently underway. One study this initiative. examines people at risk for type 1 diabetes (those who have relatives with the disease) to find out how type 1 To read more about TrialNet, visit the study’s website at diabetes occurs. The second study uses two different www.diabetestrialnet.org. ■ Research community loses talented, young scientist Melvin M. Denis, an American Diabetes Association Physician Scientist Award recipient, was tragically killed in an avalanche in the mountains near Salt Lake City, Utah on December 11, 2004. Melvin was born in Cuba and emigrated to the United States with his parents and younger sister in 1980. After earlier years of education in Florida, he was accepted to the MD/PhD program at the University of Utah in 1999 where he was pursuing research into vascular complications of diabetes as part of the requirements for the combined MD/PhD degree and with support from the ADA. His studies have resulted in reports published in the medical and scientific literature, and he will ultimately be awarded the PhD degree posthumously from the University of Utah. All who knew him agree that Melvin would have made an outstanding physician-investigator and that he brought great joy and empathy to the healing professions and to those around him. ■ 25
  • 27. American Diabetes Association funded researcher publishes new book Anne Peters, MD, former chairperson of the American basic steps for receiving good care and Diabetes Association Council on Health Care Delivery sustaining that care.” and Public Health and an ADA Clinical Research Award recipient, recently published the diabetes care book, Dr. Peters’ Clinical Research Award, What are the “Conquering Diabetes: A Cutting-Edge, Comprehensive factors associated with sustained global risk reduction Program for Prevention and Treatment.” The book in an underserved Latino population treated in a gives an overview of pre-diabetes, type 1, type 2 and diabetes disease management program?, ties in gestational diabetes, explains the various drug well with the theme of her book. Her ADA study, treatment options available to people with diabetes, performed in East Los Angeles, looks at parameters and stresses the importance of diet and exercise in associated with better outcomes among Latinos with both treating and preventing diabetes. Dr. Peters is a diabetes. The goal of her study is to determine what professor of clinical medicine at the University of tools and education people need to not only achieve, Southern California (USC) Keck School of Medicine, but maintain good health outcomes throughout their and Director of the USC Clinical Diabetes Program. lives. Her book includes photos and first-person “The reason I wrote this book,” Dr. Peters explains, accounts from patients explaining that it is possible “is because I see patients every day who do not have to prevent diabetes and treat diabetes well. good control of their diabetes even though they see Dr. Peters is happy to see her patients participate doctors. They don’t know what to ask and don’t know in their care and control their diabetes. “I see great what good care should be. This book describes the outcomes every day.” ■ 26
  • 28. Research UPdates IN THE NEWS American Diabetes Association past president authors book on diabetes and obesity crisis The New York Times reported in April 2005 that foods in school cafeterias and vending machines, and Francine Kaufman, MD, American Diabetes Association a lack of exercise among our nation’s youth. Dr. past president and research grant recipient, authored Kaufman stresses that offering children more healthful the book “Diabesity: The Obesity-Diabetes Epidemic foods and encouraging them to exercise in school and That Threatens America — and What We Must Do to in safe areas in their neighborhoods will help our Stop It” (Bantam). The article reports that Dr. Kaufman nation’s young people to reduce their chances of is treating an increasing number of children and getting diabetes. Dr. Kaufman explains, “I wrote this adolescents for type 2 diabetes, due in large part to the book to bring a face to the diabesity epidemic. My growing rate of obesity in this population. She credits book contains stories of people touched by diabetes, this rise in diabetes and obesity to the convenience and interspersed with the facts that support the gravity of low cost of unhealthy fast food, a shortage of healthy the epidemic. I wrote it as a call to action so that we can each examine how we live our lives and what we must each do to improve the environment where we work, where we live, and where our children go to school so that we might start to advocate for change.” Dr. Kaufman is a Professor of Pediatrics at the Children’s Hospital Los Angeles, and was principal investigator of the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)-funded Diabetes Prevention Trial of Type 1 Diabetes (DPT-1), to prevent type 1 diabetes from developing in individuals at high risk for the disease. She is now chair of the Studies to Treat or Prevent Pediatric Type 2 Diabetes (STOPP- T2D) steering committee. The STOPP-T2D trials are funded by NIDDK and supported by the American Diabetes Association. The trial is scheduled to begin in Fall 2005; however, the treatment trial, Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY), is currently underway at 12 medical centers around the U.S. The purpose of the TODAY trial is to study the safety and effectiveness of three different treatments for type 2 diabetes in young people. To read more about the TODAY trial, visit their website at Francine Kaufman, MD www.todaystudy.org. ■ 27
  • 29. New study reveals reason behind Atkins weight loss A March 2005 article by the Philadelphia Inquirer reported sensitivity which allowed that ADA-funded investigator Guenther Boden, MD of some of them to reduce Temple University recently concluded the first clinical trial their diabetes medications. to study the effects of the Atkins diet in a controlled They also experienced hospital setting. During the study, 10 obese patients lower triglyceride and with type 2 diabetes followed the Atkins diet for two- cholesterol levels. In Dr. weeks, limiting their carbohydrate intake to 20 grams Boden’s study, published in per day while being offered unlimited amounts of protein the Annals of Internal Guenther Boden, MD and high fat foods. While on the reduced carbohydrate Medicine, he concludes diet, the patients spontaneously reduced their caloric that the patient’s excessive overeating was fueled by intake by 1,000 calories per day and lost an average of carbohydrates. He warns, however, that the long-term four pounds each over the two-week period with at least effect of low-carbohydrate diets is unknown. This diet one patient losing 18 pounds in two weeks. According also had a low fiber content which may also lead to to Dr. Boden, the patients were not bored with the food health problems if continued over time. (Boden G, selection, and weight loss was not due to water loss or Sargrad K, Homko C, Mozzoli M, Stein TP. Effect of a a change in metabolism, but simply due to a reduction low-carbohydrate diet on appetite, blood glucose levels, in the number of calories consumed. In addition to the and insulin resistance in obese patients with type 2 weight loss, the patients who participated in the study diabetes. Annals of Internal Medicine. Mar also experienced improved glucose levels and insulin 15;142(6):403-11, 2005). ■ New drug approved for use in type 2 diabetes In the Winter/Spring 2005 issue of Forefront, we reported that researchers were investigating a new drug called exenatide in people with type 2 diabetes. The drug, a synthetic version of a hormone found in the saliva of the Gila monster, stimulates insulin secretion in humans. Amylin Pharmaceuticals, Inc. and Eli Lilly and Company have just announced that the U.S. Food and Drug Administration has approved exenatide in an injectable form to help control blood sugar in type 2 diabetes patients who are unable to achieve optimal control using oral medications (metformin and/or a sulfonylurea). Byetta (pronounced bye-A-tuh), the trade name for exenatide, is the first in a new class of medicines known as incretin mimetics. Byetta will be available in June 2005. ■ 28
  • 30. Research UPdates IN THE NEWS First Islet Cell Summit brings together researchers and donors RxPGNews.com reported that the Ford is a member of the ADA scientists’ ongoing work which reflects first American Diabetes Association Research Foundation Board of one of three major focus areas: Islet Cell Summit was held on April 8 Directors, and Edsel Ford chairs the • Genetic engineering of non- in Chicago, Illinois. At this invitation- Advisory Board of ADA’s Advocacy pancreatic cells into glucose- only event, recipients of the American Leadership Council. The seven sensitive, insulin-producing cells; Diabetes Association’s Islet Cell researchers who presented at the • Transforming stem cells or Replacement Research Awards Summit are Charles Burant, MD, pancreatic ductal cells into insulin- shared their latest findings on insulin- PhD, University of Michigan; Juan producing cells; and, producing cell replacement in type 1 Domínguez-Bendala, PhD, on behalf • Micro-encapsulation of islet cells to diabetes with donors who have of Luca Inverardi, MD, Diabetes restore normal glucose levels in supported their work, as well as invited Research Institute at the University of people with diabetes, with particular guests who had expressed an interest Miami, Leonard M. Miller School of focus on preventing rejection of in funding diabetes research through Medicine; Hengjiang Dong, PhD, these islets by the immune system. the American Diabetes Association. Children’s Hospital of Pittsburgh; Marc Garfinkel, MD, University of The American Diabetes Association’s The ADA Islet Cell Replacement Chicago; Michael German, MD, targeted research program allows Research Awards are funded in donors to specify the type of part by Cynthia and Edsel B. research they wish to fund. The Ford, II of Grosse Pointe, Summit was a great way for Michigan and Arleen and Don contributors to see firsthand how Wagner of Venetia, Pennsylvania. their generosity is advancing These families have generously diabetes research in the area committed gifts of $1.3 million they specified. It was also an and $1 million, respectively, to opportunity for the researchers to support the study of islet cell share their ideas with one another. replacement. Both families became involved with raising “As parents of a child with type 1 funds for the Association after diabetes, we have personally their children were diagnosed invested in these scientists and with type 1 diabetes. In addition their promising research, knowing Human islet. Courtesy of Steven Kahn, MB, ChB, to their financial support, these Seattle Institute for Biomedical and Clinical Research that their work brings us one step families have also contributed closer to life without diabetes for countless hours as volunteers for the University of California, San all those afflicted,” said Don and Association. Currently, Arleen Wagner Francisco; Paul Robbins, PhD, Arleen Wagner. “This summit serves as President of the ADA's University of Pittsburgh, and Ji-Won provides a unique opportunity to talk Washington County, Pennsylvania Yoon, PhD, Rosalind Franklin with and learn from those individuals Council, Don Wagner is Chair of the University of Medicine and Science. who are truly making a difference.” ■ ADA Research Foundation, Cynthia Participants heard updates on the 29
  • 31. Low birth weight linked to type 2 diabetes Researchers make strides in stem cell research A February 2005 MSNBC article ADA funded investigators Luca reports that Mary Elizabeth Patti, MD, Inverardi, MD and Ricardo a researcher at the Joslin Diabetes Pastori, PhD collaborated with Center in Boston, has discovered Juan Domínguez-Bendala, PhD that low birth weight permanently at the Diabetes Research Mary Elizabeth alters the function of insulin- Institute at the University of Patti, MD Luca Inverardi, MD Miami Leonard M. Miller School producing cells in the pancreas, thus contributing to the development of type 2 diabetes later of Medicine in Miami, Florida to discover a new way to in life. In her ADA funded Research Award, Molecular encourage embryonic stem cells to turn into islet cells. determinants of low birth weight-associated diabetes, Dr. The Miami Herald reported in March 2005 that this team Patti studied two groups of pregnant mice. She gave the successfully used a new technique to encourage mouse first group of pregnant mice all the food it wanted during embryonic stem cells to become islet cells. Before a their three-week pregnancy while restricting the diet of the stem cell can become an islet cell, it must be able to second group of mice during the final week of pregnancy. produce certain proteins in a particular sequence. One of The babies born to the food-restricted mothers weighed the road blocks in stem cell research involves the difficult 23 percent less than the babies born to mothers who task of getting stem cells to produce these proteins were not food-restricted. Dr. Patti then compared the low correctly. However, the group at the Diabetes Research birth weight baby mice to normal weight baby mice. Both Institute was able to get around this dilemma by using a groups of baby mice were fed the same diet; however, technique that delivers the necessary proteins directly to the low birth weight baby mice showed abnormally high the stem cell. After delivering the proteins to the mouse levels of blood glucose as they matured. Results from stem cells, their differentiation into islets was strongly her study revealed that the cells of the pancreas in the stimulated. The next step is to produce these same low birth weight mice were not able to produce insulin in results using human cells, which is already underway. the appropriate amounts. Even when the mice reached a (Domínguez-Bendala J, Dagmar K, Ribeiro M, Ricordi C, normal weight, this impairment was not resolved. Low Inverardi L, Pastori R, Edlund H. TAT-mediated birth weight is also a risk factor for type 2 diabetes in neurogenin 3 protein transduction stimulates pancreatic humans. Therefore, the results of this study emphasize endocrine differentiation in vitro. Diabetes. 54(3):720-726, the need for individuals of low birth weight to focus on 2005). ■ diabetes prevention, including weight maintenance and physical activity. It also demonstrates the importance of good prenatal nutrition in preventing health complications later in life. (Jiminez-Chillaron JC, Hernandez-Valencia M, Reamer C, Fisher S, Joszi A, Hirshman M, Oge A, Walrond S, Przybyla R, Boozer C, Goodyear LJ, Patti ME. Beta cell secretory dysfunction in the pathogenesis of low birth weight-associated diabetes. Diabetes. 54(3):702-711, 2005). ■ 30
  • 32. Research UPdates NOTEWORTHY ADVANCES Protein found to prevent atherosclerosis Louis Ragolia, PhD of Winthrop University Hospital and Stony Brook University in New York is working to prevent atherosclerosis, or a thickening of the artery walls, in people with diabetes. Dr. Ragolia was named the first Thomas R. Lee Award winner for his ADA Career Development Award, The molecular basis of vascular smooth muscle cell apoptosis, which began in 2002. The Thomas R. Lee Award goes to the Career Development Award applicant who receives the best peer-reviewed score Louis Ragolia, PhD on his/her application in a given fiscal year. The award not only recognizes excellence in diabetes research, but also signifies the ADA’s belief that the recipient will continue to be a premier researcher who will have great impact in diabetes treatment, prevention or the search for a cure. Dr. Ragolia’s recent research results have proven him worthy of this award. His research has shown that a protein found in blood, called L-PGDS, can prevent inflammation and control the thickening of arteries by regulating the growth of artery wall cells. He also found that L-PGDS can prevent the movement or “migration” of artery cells, an event which can lead to formation of plaques in the arteries. Finally, Dr. Ragolia found that the cells of mice with diabetes react differently to L-PGDS than the cells of mice without diabetes, and it appears that L-PGDS may reverse insulin resistance in diabetes. Dr. Ragolia will continue to study how the cells of animals with diabetes react to L-PGDS and future studies will involve development of methods or drugs to correct the reaction. ■ 31
  • 33. Two key liver signals shown to cause type 2 diabetes C. Ronald Kahn, MD and medical student Cullen Taniguchi funded by an American Diabetes Association Medical Scholars Award at Joslin Diabetes Center in Boston, Massachusetts, found that lowering the level of two key proteins in the liver can cause type 2 diabetes. By using new genetic engineering tools, they were able to turn off the two specific cellular signaling proteins (IRS-1 and IRS-2) in the liver. They also designed separate experiments and found that low levels of IRS-1 cause liver cells to make more glucose and blood sugar Cullen Taniguchi and C. Ronald Kahn, MD levels to rise. Low levels of IRS-2 are linked to high to determine how to keep levels of IRS-1 and IRS-2 up. levels of blood fats such as triglycerides. When both (Taniguchi CM, Ueki K, Kahn CR. Complementary roles IRS-1 and IRS-2 are low, diabetes occurs. Now that of IRS-1 and IRS-2 in the hepatic regulation of researchers have discovered that these two factors are metabolism. Journal of Clinical Investigation, 2005 involved in type 2 diabetes, more research can be done March 1; 115(3): 718–727.) ■ Researchers discover diabetes trigger and potential treatment mass. A new study by Drs. Shoelson levels of inflammation as well as high and Cai published in the February insulin and blood glucose levels. By 2005 issue of Nature Medicine triggering NF B to cause low-level reports on a new discovery about inflammation, they were able to NF B. cause diabetes in mice that were not at risk for the disease. Researchers are aware that obese people have livers which accumulate As in their muscle wasting study, Dr. fat quickly, and that many overweight Shoelson and Dr. Cai decided to try Dong Sheng Cai, MD, PhD and individuals with type 2 diabetes have using salicylates to reduce the Steven Shoelson, MD, PhD high levels of NF B in their livers. inflammation, and were successful. The Winter/Spring 2005 issue of Dr. Shoelson and his team found Dr. Shoelson is currently working Forefront reported that Steven that in obese mice with fatty livers, with the NIH to fund a large-scale Shoelson, MD, PhD and Dongsheng NF B was activated and caused low national trial to study the use of mild Cai, MD, PhD discovered that a levels of inflammation. They then salicylate drugs in people with factor known as NF B contributed studied lean mice without diabetes diabetes. (Cai D, Yuan M, Frantz to muscle wasting in mice. They by turning on the gene that DF, Melendez PA, Hansen L, Lee J, also found that drugs known as expresses NF B, and looking for Shoelson SE. Nature Medicine, Feb salicylates stopped NF B and signs of inflammation. The result 11(2):183-90, 2005). ■ helped the mice regain their muscle was that the lean mice showed low 32
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  • 35. Message from the American Diabetes Association Research Foundation Chair The day you learn your young, helpless child has type 1 diabetes, you start on a journey of transformation. What begins as a frightening, lonely experience can turn into an amazing, self-empowering, golden opportunity for positive change if you know where to turn for the skills, knowledge and hope that diabetes requires for living well. Our journey as parents of a child with type 1 diabetes led us to join our local American Diabetes Association office in 1986. For years, we have paid close attention to new developments in diabetes care which profoundly improved our daughter’s quality of life to the extent that she is now married and has a healthy child of her own. By finding new ways to fight diabetes, everyone is encouraged to work harder and it is research that makes these improvements in treatments possible. Today, I and my wife, Arleen, continue to be involved locally and nationally with the ADA. Naturally, we are drawn to research and have often discussed state-of-the-art diabetes research with some of the world’s most prominent scientists funded by the ADA Research Foundation. We know that we are making remarkable progress, yet our work is far from over. While the federal government is doing what it can to fund diabetes research, it is not doing enough to keep up with the widespread growth of the fastest developing, chronic disease of our time. This adds greater urgency to the work of the American Diabetes Association and our Research Foundation. Founded in 1994, the ADA Research Foundation was created to accelerate the Association's ability to raise major gifts to directly fund diabetes research. To date, the Foundation has contributed more than $46 million to diabetes research and has single-handedly transformed the breadth and depth of the ADA Nationwide Research Program, giving it greater prestige and purpose and, above all, its unique ability to match a donor's interests and dollars with leading-edge diabetes research projects. On page 15, you’ll find an excellent example of inspiring, donor-driven research funded by California philanthropists, Terry and Louise Gregg. Recently, the Research Foundation was also responsible for bringing together seven of the world’s most accomplished type 1 diabetes researchers to brief donors on their progress at our first Islet Cell Summit held this past spring in Chicago. Donors saw firsthand the powerful impact their support is making in helping researchers develop replenishable sources of cells that could restore the body’s ability to produce insulin. Philanthropy has always played the most prominent role in supporting the ADA’s commitment to life without diabetes— so much so that we feel empowered to reach our $300 million goal by 2010 if that’s what it takes to defeat diabetes in our lifetime. Please join us in our journey toward life without diabetes. To learn more about donor-driven research projects or any aspect of the Research Foundation, Pinnacle Society or Summit Circle, please contact Ms. Elly Brtva, Managing Director of Individual Giving at (800) 676-4065, ext. 4377 or ebrtva@diabetes.org. Thank you for your ongoing support. Sincerely, Don Wagner 34
  • 36. Did you know? • Of the 18.2 million Americans with diabetes, it is estimated that 5.2 million of them do not even know they have the disease. • Another 41 million Americans have pre-diabetes, a condition in which blood sugar levels are higher than normal but not quite high enough for a diagnosis of diabetes. People with pre-diabetes are at increased risk for developing diabetes. • To date, the American Diabetes Association has invested more than $350 million in diabetes research throughout the nation. • The Association places a strong emphasis on supporting young scientists and providing training awards to new, talented researchers who benefit from receiving a young investigator award before moving on to obtain larger grants. The American Diabetes Association’s Annual Scientific Sessions is the largest annual research and clinical meeting on diabetes. This year’s annual meeting June 10-14, 2005 • San Diego, California was held June 10-14, 2005 in San Diego, California. To find out more about the scientific information presented at the meeting, log on to www.scientificsessions.diabetes.org 1-800-DIABETES IndividualGiving@diabetes.org 1701 N. Beauregard Street Alexandria, VA 22311

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