I am pleased to present the Fiscal Year (FY) 2007 President's budget request for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) a sum of $1,844,298,000, which includes $150,000,000 for the Special Appropriation for Research on Type 1 Diabetes through Sec. 330B of the Public Health Service Act. The NIDDK transfers some of these funds to other institutes of the NIH and to the Centers for Disease Control and Prevention (CDC). Adjusted for mandatory funds, this is an decrease of $10,627,000 from the FY 2006 enacted level of $1,854,925,000 comparable for transfers proposed in the President's request.

The NIDDK supports research to combat a wide range of chronic health problems, including diabetes and other endocrine and metabolic diseases; diseases of the digestive system, kidneys, urinary tract; and blood; nutritional disorders; and obesity. Through vigorous research, initiated both by investigators and by the Institute, the NIDDK will continue to elucidate the fundamental biology underlying health and disease. We are pursuing new strategies for disease diagnosis, treatment, and ultimately, prevention and cure.

PREEMPTING CHRONIC DISEASES AND THEIR COMPLICATIONS

Chronic diseases pose some of the greatest health challenges to the Nation today. These diseases and their symptoms range in severity, but are often debilitating and sometimes fatal. Some impair fundamental body processes, such as metabolism, while others target the kidneys, liver, and other vital organs and systems. Though their causes and ultimate effects on health may differ, chronic diseases share the grim features of constant affliction and impaired quality-of-life. The burden of chronic diseases within NIDDK's research purview is immense. Recent estimates using national health survey data reveal that diabetes (type 1 and type 2) affects nearly 21 million Americans. About 20 million Americans have chronically impaired kidney function, which places them at increased risk for irreversible kidney failure (end stage renal disease) and death. Digestive diseases, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and liver and biliary diseases, wreak havoc with people's lives. "Benign" diseases of the bladder and lower urinary tract, including urinary incontinence and prostate diseases, can be devastating. These chronic diseases also exact a heavy economic toll. For example, the healthcare and indirect costs of diabetes and its complications totaled $132 billion in 2002. The painful, debilitating symptoms of IBS and the bladder disease interstitial cystitis (IC) result in loss of work and increased medical costs. Costs of chronic diseases that strike the digestive system, kidneys, and bladder run into the tens of billions of dollars.

The tremendous human and monetary costs of chronic disease are matched only by the extraordinary interventions often needed just to preserve life. Organ transplantation and kidney dialysis are but two examples. Although these are extreme measures for the sickest patients, they represent some of the victories achieved by biomedical research in reducing morbidity and mortality from advanced chronic disease. Our goal is to improve these treatments, while we simultaneously seek prevention strategies. For example, whole liver transplantation from deceased donors is a successful treatment for liver failure, but is limited by a shortage of donor organs. A new NIDDK clinical network (A2ALL) is maximizing this treatment option in adults by assessing the safety and outcomes, for both patients and donors, of new procedures that use partial liver transplants from living donors--thereby increasing the potential donor pool. Similarly, we are addressing the diminished quality-of-life and low five-year survival rates under current dialysis treatment, which is typically administered three times weekly. A new clinical trial will evaluate the effectiveness of daily dialysis.

IMPORTANCE OF EARLY INTERVENTION

For persons already suffering from chronic disease, improved treatments will have great benefits. However, it is imperative that researchers find ways to intervene at the earliest possible stage of a disease. The goals for such research are to: (1) identify and use biological information, such as "biomarkers," that can predict an individual's susceptibility to disease, disease progression, or disease complications--thereby enabling more tailored use of interventions; (2) find the most effective interventions to preempt the onset or course of disease; and (3) ensure that these predictive tools and interventions can be precisely targeted for the benefit of patients. New advances in science, technology, and public health research are making these goals realizable, with the prospect of significant improvements in public health. Examples of potential research payoffs include hepatitis C and diabetes complications. In the U.S., hepatitis C infection affects an estimated four million people and is the leading cause of both liver cancer and liver failure due to end-stage cirrhosis. Patients who do not respond to standard medical therapy with interferon and ribavirin are at high risk of developing these severe health problems. Ideally, physicians should be able to predict likely "non-responders" to current therapy and those at risk for disease progression, and then tailor interventions to them. While this is not yet possible, ongoing studies will help to move the field forward, including a major clinical trial (HALT-C) aimed at preventing end-stage cirrhosis and lowering risk of liver cancer in "non-responders" with advanced disease.

Likewise, physicians would welcome new, precise methods for tailoring interventions to individuals with diabetes so as to reduce complications in those at greatest risk, while also lessening treatment burden. Landmark clinical trials have demonstrated that tight control of blood sugar levels in type 1 diabetes patients significantly reduces their overall risk of eye, kidney, nerve, and cardiovascular disease. Unfortunately, current therapies to achieve tight control also increase the risk of potentially life-threatening bouts of low blood sugar. If a simple method existed to identify patients who could tolerate "looser" control of blood sugar levels without an increased risk of complications, then therapy could be tailored accordingly. Pinpointing the underlying causes of diabetes complications will pave the way to such targeted interventions.

Developing a more personalized approach to medical therapy requires a robust toolkit forged from research advances. Therefore, the NIDDK is continuing with new initiatives to accelerate translation of fundamental research into clinically useful applications. For example, we want to be able to stop early scarring of the liver and kidney--known as fibrosis--before it ignites a series of events leading to irreversible organ failure. The NIDDK is fostering new, non-invasive imaging methods to reveal fibrosis. Such techniques will enable physicians to diagnose, monitor and treat liver and kidney disease more effectively. For diseases within the NIDDK mission, we are also committed to the discovery of biomarkers--factors, such as molecules, that can be measured and used to monitor a patient's disease or response to therapy. A new translational initiative encourages research to develop and validate these biomarkers for clinical use.

Critically important for predicting and preempting chronic diseases--such as polycystic kidney disease (PKD), focal segmental glomerulosclerosis (FSGS), kidney stones, IC, IBD, IBS, non-alcoholic steatohepatitis (NASH), and hepatitis B and C--is a thorough understanding of their natural history. For example, discovery of PKD genes has led to insights into the molecular defect underlying most cases of this disease. Promising new medical therapies are being explored to prevent or reduce cyst formation, and new trials (HALT-PKD) will now test approaches for preventing progressive kidney damage. In the kidney disease FSGS, we do yet know all the causative factors, but a better understanding of FSGS progression has enabled the NIDDK to undertake a trial of therapies to prevent or delay kidney failure in patients. A new international patient registry should increase our understanding of inherited causes of calcium oxalate kidney stones. The cause(s) of the bladder disease IC remains unknown, but studies of a promising biomarker from urine may lead to improved diagnosis and treatment for patients, as well as to new therapeutic options.

Our efforts in digestive diseases will be guided by a long-range strategic research plan to be developed by a new National Commission, as well as by a recently completed Liver Disease Action Plan. We are already making progress on several fronts. In IBD, studies of a recently identified Crohn's disease susceptibility gene are pointing the way to new therapeutic options. Researchers are exploring the multiple physical and cognitive factors that appear to play a role in IBS. A new clinical research network is studying the biological basis of progression from a less serious form of non-alcoholic fatty liver disease to the fatty liver, liver inflammation and scarring of NASH, and will test strategies to prevent disease progression in both adults and children. Studies of the hepatitis B virus continue in order to optimize treatment options. A new system to replicate ("grow") hepatitis C virus in the laboratory will significantly enhance research to test potential therapeutic targets and open the door to vaccine development--complementing ongoing trials such as HALT-C.

Strikingly, research has revealed that obesity, with its comorbidities, is at the nexus of many chronic diseases. The high prevalence of obesity in the U.S. population, with nearly 31 percent of adults affected, bears directly on the millions affected with chronic diseases. Obese individuals are at increased risk of type 2 diabetes, and obesity is linked to increased risk of NASH, as well as of ESRD via type 2 diabetes and high blood pressure. However, not all overweight and obese individuals will develop obesity-associated diseases. Age, gender, race, ethnicity, socio-economic status, and individual genetics are among the many factors that may influence risk. Through initiatives developed by the NIH Obesity Task Force and through NIDDK-led efforts, we are encouraging research studies to promote prevention and to identify which subsets of obese individuals are at risk for developing particular comorbidities, and, in turn, to tailor interventions accordingly.

Recent data offer promise that we may be able to stem the tide of obesity-related health problems. For example, analyses by the United States Renal Data System (USRDS) indicate that overall incidence rates of ESRD have stabilized in the U.S., following a 20 year period of annual increases. This finding suggests that there has been a successful translation into medical practice of research-based knowledge important to preventing ESRD--the use of medications (ACE inhibitors) and the benefits of controlling blood sugar and blood pressure levels. Unfortunately, this positive result has not yet been seen across the entire U.S. population, in that ESRD continues to affect minority groups disproportionately. The National Kidney Disease Education Program (NKDEP) has a major campaign aimed at reducing the burden of kidney disease in African Americans, for whom the risk factors of high blood pressure, diabetes, and a family history are dangerous red flags. Through its working groups, the program is also promoting the standardized, routine reporting of serum creatinine--an indicator of kidney function. Use of this simple approach can facilitate early detection and treatment of impending or active chronic kidney disease in patients. Along the same lines, the National Diabetes Education Program (NDEP) has translated into a multi-faceted campaign for multiple audiences the impressive results of the Diabetes Prevention Program (DPP) clinical trial. This trial demonstrated that lifestyle changes--relatively moderate weight loss and increased physical activity--can reduce the risk of type 2 diabetes by 58 percent in persons at risk for the disease.

Such hopeful results spur our efforts to further reduce the health burden of these chronic conditions through interventions to prevent obesity as early as possible. Prevention research needs to address the alarming rise in rates of pediatric overweight and obesity nationwide over the past three decades. A recent study indicates that approximately two million American adolescents have a prediabetic condition (IFG) strongly linked to obesity and overweight. Children and adolescents are being increasingly diagnosed with type 2 diabetes, NASH, and other obesity-associated conditions once found mainly in adults. To address key points of vulnerability early in life, the NIDDK is spearheading several initiatives, such as defining mechanisms by which maternal obesity and diabetes during pregnancy affect the future risk of obesity and other chronic diseases in offspring. Another initiative is focused on finding ways to prevent or manage weight gain in children. Moreover, the new "HEALTHY" trial will investigate whether a concerted, integrated program in middle schools will help reduce the prevalence of obesity-related harbingers of type 2 diabetes by improving cafeteria lunches, vending machine offerings, and physical education and promoting behavioral change. The tremendous success of the intensive lifestyle intervention for adults in the Diabetes Prevention Program provides hope that the HEALTHY trial may do the same for children.

The Nation's investment in NIH-funded research offers enormous benefits, particularly the opportunity to preempt disease and reduce its lifelong costs, both human and economic. To this end, the NIDDK is harnessing new technologies, maximizing research investments, and capitalizing on new opportunities to achieve early, effective intervention for the many chronic diseases within its mission. Thank you, Mr. Chairman. I would be pleased to answer any questions that the Committee may have.

Dr. Rodgers is the Acting Director, National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), effective March 6, 2006. Prior to this appointment, he had served as Deputy Director, NIDDK, since 2001. Dr. Rodgers also serves as chief of NIDDK's Clinical and Molecular Hematology Branch, which he has headed since 1998. Dr. Rodgers received his undergraduate, graduate and medical degrees from Brown University in Providence, R.I. He did his residency and chief residency in internal medicine at Barnes Hospital, Washington University School of Medicine in St. Louis, Missouri. His fellowship training in hematology/oncology was in a joint program of the NIH, George Washington University and the Washington Veterans Administration Medical Center. Dr. Rodgers is widely recognized for his contributions to the development of the first effective--and now FDA-approved--therapy for sickle cell anemia. He has served as the principal investigator in clinical trials to elevate pharmacologically fetal hemoglobin to counteract the deleterious molecular and cellular effects present in the red cells of these patients. Dr. Rodgers' basic research has focused on understanding the molecular basis of how these drugs induce gamma-globin gene expression. He was honored for his research with the 1998 Richard and Hinda Rosenthal Foundation Award and the 2000 Arthur S. Fleming Award, among others. He has published over 150 original research articles, reviews, book chapters and books, including the recent Bethesda Handbook of Clinical Hematology. Dr. Rodgers served as Governor to the American College of Physicians for the Department of Health and Human Services, and is a member of the American Society of Hematology, the American Society of Clinical Investigation, and the Association of American Physicians. He is the Chair of the Hematology Subspecialty Board, and is a member of the ABIM Board of Directors.