Contents Director’s Message Overview .............................................................................................................................................. 1 Cross-Cutting Research ..................................................................................................................... 3 Diabetes, Endocrinology, and Metabolic Diseases ........................................................................ 7 Digestive Diseases and Nutrition .................................................................................................... 25 Obesity ............................................................................................................................................... 37 Kidney, Urologic, and Hematologic Diseases .................................................................................. 43 Intramural Research .......................................................................................................................... 53 NIDDK and the Nobel Prize ............................................................................................................ 62 How NIDDK Supports Research ....................................................................................................... 65 NIDDK Directors ............................................................................................................................... 67 Acknowledgements ......................................................................................................................... 69 Director’s Message CELEBRATING 60 YEARS OF RESEARCH DISCOVERY AT THE NIDDK As the ninth Director of scientists who will carry forth these efforts into of the National the future. To identify key research challenges and Institute of Diabetes opportunities and maximize the health return on and Digestive and research investments, the Institute engages in strategic Kidney Diseases planning with broad stakeholder input. Through (NIDDK), it is my great our education and outreach programs, the NIDDK honor to present disseminates science-based health information to this compendium, in patients, healthcare providers, and the public. which we celebrate the Institute’s Ground-breaking scientific research has been driven accomplishments forward by the efforts of dedicated investigators, as over the past 60 years well as the participation of patients in clinical research. in supporting and The Institute is deeply grateful to the patients and conducting research families who participate in NIDDK research studies to on some of the most common, chronic, and costly benefit others affected by disease. The perspectives diseases affecting people in this country and around of some of these patients are highlighted in this the world, as well as on diseases and disorders which compendium. are less widespread but nonetheless devastating in their impacts. The research highlighted here represents just a sampling of the Institute’s past and current efforts and Diseases and disorders within the NIDDK’s mission future plans. For additional information, I encourage include diabetes and other endocrine and metabolic you to visit our web site at: www.niddk.nih.gov. diseases, digestive and liver diseases, nutritional disorders, obesity, kidney and urologic diseases, and We hope that you enjoy this retrospective tour of diseases of the blood. Many of the NIDDK’s research NIDDK-supported research achievements as we look programs cut across boundaries of disease and forward to building on this progress to propel scientific discipline through their applicability to multiple areas discovery in the years ahead toward improving the of biomedical inquiry and a range of diseases. nation’s health. Throughout its history, the NIDDK has remained committed to supporting vigorous basic, clinical, and translational research efforts by extramural scientists GriffinP. Rodgers, M.D., M.A.C.P. at academic and other medical research institutions Director throughout the country, as well as by scientists in the National Institute of Diabetes and Digestive and Institute’s Intramural Research Program. The NIDDK Kidney Diseases also maintains strong support for research training National Institutes of Health and career development for the next generation U.S. Department of Health and Human Services Overview MISSION AND ORGANIZATION OF THE to the scientific peer-review process for assessing INSTITUTE: The National Institute of Diabetes grant applications. The NIDDK is also home to and Digestive and Kidney Diseases (NIDDK) the National Institutes of Health (NIH) Division of conducts and supports research on many serious, Nutrition Research Coordination, which provides chronic diseases: diabetes and other endocrine advice and coordination for nutrition research. The and metabolic diseases and disorders; digestive NIDDK’s Division of Intramural Research consists diseases; nutritional disorders; and kidney, urologic, of government scientists who conduct research and hematologic (blood) diseases. across a broad spectrum of basic and clinical topics. With respect to clinical research, extramural and The NIDDK’s Division of Diabetes, Endocrinology, intramural, the research progress since the Institute’s and Metabolic Diseases (DEM) supports basic and establishment reflects the contributions both of clinical research in the areas of diabetes; obesity; NIDDK-supported investigators and of the patient cystic fibrosis; osteoporosis; and other, often volunteers in clinical studies. The Institute also rare, endocrine and genetic metabolic diseases. supports research training for students and scientists The Division of Digestive Diseases and Nutrition at various stages of their careers, and a range of (DDN) supports research toward understanding, education and outreach programs that aim to bring preventing, and treating diseases of the esophagus, science-based information to patients and their stomach, intestines, liver and biliary system, and families, healthcare professionals, and the public. pancreas, as well as research on obesity and basic nutrition research. The Division of Kidney, ESTABLISHMENT AND HISTORY OF THE Urologic, and Hematologic Diseases (KUH) supports INSTITUTE: On August 15, 1950, President Harry research into chronic kidney disease and kidney S. Truman signed the Omnibus Medical Research failure, urologic diseases, the development of the Act (P.L. 81-692) into law, establishing the National genitourinary tract, and hematologic diseases. Institute of Arthritis and Metabolic Diseases, the The DEM, DDN, and KUH Divisions all support forerunner to the NIDDK. In the ensuing years, the extramural research—research by scientists at Institute was renamed several times. In 1986, one of universities and other medical research institutions the Institute’s former Divisions became the core of a throughout the country. The Institute’s Division of new, separate NIH component focused on arthritis Extramural Activities provides leadership, oversight, and other diseases, and the Institute acquired its tools, and guidance to manage the Institute’s grants current name: the National Institute of Diabetes and policies and operations, including efforts related Digestive and Kidney Diseases—the NIDDK. 1 Cross-Cutting Research dvances in medicine are largely dependent upon the accumulation of new knowledge about A biologic processes, often at the smallest levels of an organism—its genes, the proteins they encode, and the workings of and communications between cells. In many cases, major strides in fighting disease can be traced back to laboratory studies whose immediate relevance to health could not have been fully known or appreciated at the time they were conducted. Opportunities to make exciting new discoveries and advances are arising ever more rapidly with the development of new technologies, new approaches, and even new scientific disciplines. Described here are studies that span scientific boundaries, including research on fundamental biologic processes as well as the development of new technologies that make such studies possible. The insights gained through this type of research can be expected to propel disease- oriented research, not only within the NIDDK mission, but also in many other fields, for today’s cross-cutting advances may lead to tomorrow’s new treatments. Genome-wide Association and Other Genetic Studies: NIDDK-supported scientists have discovered many genetic variants that influence a person’s likelihood of developing different diseases. Genetic findings have greatly accelerated in recent years as a result of the Human Genome Project and related efforts, including the development of the HapMap, a collection of many thousands of common genetic variants, called “SNPs,” throughout the Data from a genome-wide association study of inflammatory bowel disease, genome. Genome-wide association studies (GWAS) which identified genetic variations associated with disease susceptibility. rely on these research tools and advanced technologies Image credit: Rioux J. et al. Reprinted by permission from Macmillan Publishers Ltd: Nat Genet, 39: 596-604, copyright 2007. to identify genetic differences between people with specific illnesses and healthy individuals. In some cases, risk of type 2 diabetes. One genetic region previously the genetic association maps to a chromosomal region found to be strongly associated with type 2 diabetes has that had not been thought to play a role in biological recently been implicated in a very different condition: