Mr. Chairman and Members of the Committee: I am pleased to present the President's budget request for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for FY 2005, a sum of $1,876,196,000, which includes $150 million 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 increase of $54,956,000 over the FY 2004 enacted level of $1,821,240,000 comparable for transfers proposed in the President's request.

HIGHLIGHTS OF PROGRAM ENHANCEMENTS

I appreciate the opportunity to testify on behalf of the NIDDK's efforts to combat the wide range of debilitating, chronic health problems within our research mission, many of which are caused directly or indirectly by obesity. Last year, I reported the creation of an NIDDK Office of Obesity Research to intensify the fight against this major public health problem, which is harmful both in its own right and as a driver of type 2 diabetes, especially in minorities and the young. Obesity can also be a contributing factor to nonalcoholic fatty liver disease, gallstones, end-stage kidney disease, and urinary incontinence. According to the CDC, approximately 64 percent of adults and 15 percent of children and teens are considered either overweight or obese. Disturbingly, these rates reflect skyrocketing trends over the past two decades. To accelerate research to combat this epidemic, the NIH Director established the NIH Obesity Research Task Force in April 2003, with co-chairmanship by the Directors of the NIDDK and the National Heart, Lung, and Blood Institute (NHLBI). I am pleased to report that the Task Force has completed a draft Strategic Plan for NIH Obesity Research, with input from external scientific and lay experts. This Plan is posted on a newly established Web site that will alert investigators to NIH obesity research funding opportunities, and also inform the public about NIH efforts. Both the Plan and the Web site are dynamic, and will evolve with changes in science and public health needs. Acting alone, the NIH cannot halt or reverse obesity; however, by generating and disseminating new research knowledge, we can lend a vital scientific dimension to what must truly be a multifaceted national effort.

The Strategic Plan will contribute to the prevention and treatment of obesity by bolstering research in three major avenues: (1) behavioral and environmental approaches to modify lifestyle; (2) pharmacologic, surgical, or other biological/medical approaches; and (3) ways to break the link between obesity and its associated health conditions, known as co-morbidities. Within the goals and strategies outlined in the Plan, the NIDDK will have a major role in three trans-NIH initiatives.

The first is an effort to combat pediatric obesity in site-specific ways--both in primary-care settings, and in other community settings, such as the home, day-care, pre-school, school, and other venues. Researchers will explore effective methods for the primary prevention of inappropriate weight gain among children and adolescents who are not overweight; secondary approaches to prevent further weight gain among those already overweight or obese; and tertiary efforts to prevent co-morbidities. We will build on studies the NIDDK is already pursuing to evaluate the effects of so-called "natural experiments" in which States or localities are changing the food and lifestyle choices and cues that students encounter in school settings. We will also build on studies to determine the effects of modifying the home environment, such as the influence of T.V.-watching on obesity, eating behavior, and physical activity. Our children are precious, and we should do all we can to spare them the serious health problems that can attend a lifelong struggle with obesity.

A second trans-NIH initiative will focus on the neurobiological basis of obesity, which includes the intricate brain-gut circuits that signal hunger and fullness, and thus are crucial to maintaining the body's energy balance between calories consumed as food and expended in physical activity. I previously reported on several hormones that mediate energy-related signals, such as leptin, adiponectin, and ghrelin. By exploiting these and other findings through innovative collaborations between biomedical and behavioral researchers, we will delineate the many pathways that modulate the control of eating behavior in humans.

In a third trans-NIH initiative, the NIDDK will take the leadership role in creation of an Intramural Obesity Clinical Research Program to capitalize on the unique, collaborative infrastructure of the NIH Clinical Research Center. This Program will foster multidisciplinary approaches to obesity research in areas such as metabolism, endocrinology, nutrition, cardiovascular biology, liver and other digestive diseases, genetics, and the behavioral sciences. A "magnet" approach will draw upon the extensive expertise and resources of the NIH intramural program to frame state-of-the-art clinical investigative strategies and harness emerging technologies.

In addition to these trans-NIH initiatives, the NIDDK will support a range of research, including ancillary studies to maximize the resources already invested in ongoing clinical trials. We will pursue challenging questions about obesity. What factors control where fat is deposited, and the relationship between its location and differences in metabolism, fat-cell regeneration, cell signaling, and associated co-morbidities of obesity? What is the relationship between obesity and abnormal levels of circulating and stored lipids, which are a hallmark of metabolic problems? Can we identify biomarkers of change brought on by the obese state? What genetic abnormalities underlie the co-morbidities of obesity? What steps can people take to achieve long-term maintenance of weight loss?

As obesity is escalating in the U.S., so is type 2 diabetes. New estimates from the CDC place the number of people with diabetes at 18.2 million, and about 90-95 percent of them have this form of the disease. Disturbingly, about 5.2 million of those affected are unaware. Millions of adults also have a condition called "pre-diabetes," in which glucose levels are elevated, but not as high as in full-blown diabetes. Because clinical trials have demonstrated that lifestyle and medical interventions can significantly delay or prevent disease onset in those at high risk, it is critical to identify these individuals and underscore the preventive actions they can take. The NIDDK is taking vigorous steps to foster the generation of new laboratory tests to improve diabetes detection, as well as to promote the development of more cost-effective strategies to pinpoint those at risk who can benefit most from early intervention. We are also supporting studies to translate important advances from clinical trials in diabetes prevention and care into medical practice. For example, for a low-income Latino population, we are supporting a clinical trial to compare current translation efforts for type 2 diabetes prevention with a method that incorporates culturally-sensitive strategies. We are also studying an interactive video conferencing system to enable communication between health professionals at a large medical center and diabetes patients in a rural state, with limited access to health care providers. Interventions that are successful in these trials could pave the way to widespread use by communities throughout the country.

Once considered an "adult-onset" disease, type 2 diabetes is being increasingly diagnosed in children and adolescents, especially in minority populations. We are launching a multi-center, school-based trial (STOPP-T2D) to find ways to prevent the development of risk factors for type 2 diabetes in middle-school children. The trial will include school-based programs targeting nutrition, physical activity, and behavior modification. Another multicenter trial (Treatment Options for Type 2 Diabetes in Adolescents and Youth-TODAY) will seek the best treatment strategies.

Diabetes can lead to serious complications, such as blindness, irreversible kidney failure, lower limb amputation, and heart disease. We have established an NIDDK Diabetes Complications Working Group, which is charged with seamless integration of these activities across the Institute. The NIDDK also recently convened an international group of clinical and basic researchers to brainstorm research approaches to the urologic complications of diabetes. Because complications can affect many organs, we collaborate with other components of NIH and the Department to benefit from their expertise. For example, studies have shown that the process of new blood vessel formation, called "angiogenesis"--traditionally studied in relation to cancer--is also critically important to vascular changes in diabetes, such as the dangerous proliferation of blood vessels in the eye that can lead to blindness. Angiogenesis will be the central theme of a new research collaboration involving multiple NIH institutes.

In an aggressive research program on type 1 diabetes, we have established unique, innovative, and collaborative research groups, clinical trial networks, and consortia, with an overarching group to standardize and coordinate their efforts. We are also working to overcome barriers that currently prevent widespread clinical research on islet transplantation to restore normal insulin-producing capacity to patients. In collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), we are establishing a national consortium to step up progress toward general clinical applicability of islet transplantation.

To spur research in digestive diseases, the NIDDK recently established a new Liver Disease Branch within its Division of Digestive Diseases and Nutrition. With expert external input, this Branch is now spearheading the development of a Liver Disease Research Action Plan under the auspices of the Digestive Diseases Interagency Coordinating Committee. As requested by the Congress, the NIDDK is submitting a report on actions taken by the NIH and other HHS components in response to recommendations from a Consensus Conference on hepatitis C. In other research, broad approaches are providing insights into the inflammatory bowel diseases--Crohn's disease and ulcerative colitis. Fundamental studies are shedding light on the development of pathways that control gut motility; integration of pain, motility and behavioral neural circuits; and gut inflammation.

For polycystic kidney disease (PKD), a research consortium has established the value of Magnetic Resonance Imaging for measuring kidney size. This advance portends dramatic improvements in assessing disease progression--a critical step in developing and evaluating new treatments. The HALT-PKD Network is testing a regimen designed to lower blood pressure and slow disease progression--the first of several clinical studies envisioned. A workshop on oxalosis and primary hyperoxaluria--an inherited cause of kidney stone disease--has identified future clinical research directions, which will apply emerging knowledge about underlying metabolic and genetic abnormalities. We have also launched or expanded initiatives on interstitial cystitis, urinary incontinence, and urinary tract infections, consistent with the scientific recommendations of the Strategic Plan of the Bladder Progress Review Group. A recently formed Interstitial Cystitis (IC) Epidemiology Task Force is guiding efforts in that area, as described in a requested report to the Congress.

TRANSLATION RESEARCH AND ROADMAP EFFORTS

Underpinning our disease-focused programs is an emphasis on "translation" research, which benefits patients directly by bringing the fruits of laboratory discoveries into the arena of clinical research, and by propelling the positive results of clinical trials into medical practice. In one promising pilot effort to speed the development of therapies for type 1 diabetes, we are building on an innovative mechanism established by the NCI called "Rapid Access to Intervention Development." We are also pursuing several translational efforts related to the NIH Roadmap for Biomedical Research. These include development of non-invasive methods for diagnosing and monitoring the progression of diabetes, kidney and digestive diseases; harnessing new technologies such as proteomics-the study of proteins and their functions; as well as studying stem cells during human development and tissue repair. We are leading an NIH Roadmap initiative in "New Pathways to Discovery" by enhancing metabolomics--the study of networks within the cell, and constituents of the cell, such as carbohydrates, lipids, and amino acids. We are also playing a major role in Roadmap efforts to build "Research Teams of the Future" by spurring interdisciplinary research training. These efforts can benefit programs within the NIDDK mission by bridging scientific disciplines and catalyzing partnerships, such as collaborations between biomedical and behavioral researchers, which are so important to moving obesity research forward.

Today, I have presented a cameo of our many and diverse research efforts and plans. Our research momentum has never been greater, and our commitment to improving health remains clear and strong.

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases
Biographical Sketch

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William R. Beldon
Mr. Beldon is currently serving as Acting Deputy Assistant Secretary for Budget, HHS. He has been a Division Director in the Budget Office for 16 years, most recently as Director of the Division of Discretionary Programs. Mr. Beldon started in federal service as an auditor in the Health, Education and Welfare Financial Management Intern program. Over the course of 30 years in the Budget Office, Mr. Beldon has held Program Analyst, Branch Chief and Division Director positions. Mr. Beldon received a Bachelor's Degree in History and Political Science from Marshall University and attended the University of Pittsburgh where he studied Public Administration. He resides in Fort Washington, Maryland.