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FOCUS FOR NUTRITION RESEARCH

Question. It has been stated that five of the 10 leading causes of death have been associated with dietary habits (U.S. Dept. of Health and Human Services, The Surgeon General's Report on Nutrition and Health, 1988). In fact, it is believed that some 30 percent to 60 percent of all cancers may be associated with diet (National Research Council, Diet, Nutrition and Cancer, 1982). Given this close relationship of diet and nutrition to human disease, it is surprising to find that there is no clear focus for nutritional research at NIH. Can you explain why this is the case?

Answer. There is a clear focus for nutrition research provided by the NIH Nutrition Coordinating Committee, which is a catalyst for trans-NIH meetings, conferences, and research solicitations in this field, as well as the mechanism for providing a cross-fertilization and interchange of research activities and plans among the institutes. Primary research activity in nutrition remains at the institute level, consistent with the research orientation of each NIH component. For example, nutrition research as it relates to cancer is funded by the National Cancer Institute. Similarly, nutrition research as it relates to heart disease is funded by the National Heart, Lung and Blood Institute. Fundamental nutrition research in such areas nutrient metabolism is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. We believe this organizational approach is the most appropriate one for nutrition research. In FY 1992, 15 NIH components will collectively spend approximately $323.2 million on nutrition research.

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OBESITY RESEARCH

Question. Obesity appears to figure importantly as one of the chief nutritional disabilities provoking untimely death from diabetes, heart disease and other ailments. The NIH, some years ago, played a central role in pointing out the importance of obesity in a Consensus Conference. Yet, treatment appears to be of uncertain quality and non uniformly helpful. Why has NIH not had an additional Consensus Conference to inform the medical profession and the Ameerican public on what constitutes optimum treatment? Shouldn't the medical profession and American public know whether there is a recommended treatment?

Answer. I'm pleased to tell you that the NIH sponsored a Consensus Development Conference on "Gastrointestinal Surgery for Severe Obesitys on March 25-27, 1991. This conference evaluated the objective data for new surgical procedures developed in the last 10 to 15 years, which use principles of reduction of gastric volume, intestinal malabsorption, or both. Refinements in these procedures have led to reports of successful results superior to those seen with the earlier intestinal bypass operations. In addition, the National Institute of Diabetes and Digestive and Kidney Diseases is in the process of establishing a National Task Force on the Prevention and Treatment of Obesity. Comprised of eminent scientific experts, this Task Force will review the current stateof-the-science from a clinical perspective and develop a consensus about preventive and therapeutic approaches. The Task Force will also identify issues for future clinical study. At the same time,

the NHLBI is exploring the possibility of establishing a new program that would focus on obesity as a risk factor for hypertension. The Nutrition Coordinating Committee is also very active with respect to obesity. It has established a Work Group on Obesity that has met monthly since last June; is planning a major conference on obesity for 1991; developing Requests for Applications, Requests for Proposals, and Program Announcements related to obesity; and focusing special attention on prevention of obesity in its annual report. I think that all of these efforts are contributing to a greater understanding of obesity and its treatment and prevention, and that the American public will benefit as a result.

OBESITY PREVENTION RESEARCH

Question. Isn't there more to nutrition than simply cajoling people to eat a different diet? Is there no scientific base that can be generated by clinical investigation which will determine how diseases such as obesity can be prevented?

Answer. I agree that we need to have some general guiding principles about the treatment and prevention of obesity and that these principles need to have a sound scientific basis. Developing such principles is one of the major objectives of a new National Task Force on the Prevention and Treatment of Obesity, which the National Institute of Diabetes and Digestive and Kidney Diseases is in the process of establishing.

GENETIC/METABOLIC FACTORS IN NUTRITION

Question. What are the NIH initiatives to bring modern molecular biologic science into nutrition?

Answer. The techniques of modern molecular biology are being applied to nutrition research in many ways. One avenue is the study of genetics in obesity, along with the search for metabolic factors that may regulate the storage of fat at the cellular and molecular levels. The National Institute of Diabetes and Digestive and Kidney Diseases is in the forefront of fundamental research in these areas. Recently, the NIDDK and the NICHD issued a joint solicitation to encourage additional research grants on the genetic and metabolic factors associated with the development of obesity in childhood, adolescence and adulthood. In addition, research efforts would focus on genetic and metabolic factors discernible in childhood that predict the onset of obesity later in life. Applications received in response to this RFA have now received initial review, and pending secondary review, it is expected that several will be funded.

NUTRITION RESEARCH TRAINING

Question. Are there a pool of physicians who are trained to do research in nutrition? Are these physicians learning modern scientific skills in molecular biology?

Answer. Yes, there is such a pool, but it would benefit from expansion. To this end, the National Institute of Diabetes and Digestive and Kidney Diseases has taken the initiative in

soliciting additional research trainees in the nutrition sciences through publication of annual Requests for Applications. Two such solicitations have been issued, and a third will be published in 1991, which will specifically encourage applications for career awards and fellowships. During FY 1990, three new institutional training grants were awarded, which will enable institutions to offer support to promising individuals for pre- and postdoctoral training. In addition, an institutional Physician Scientist Award to support newly trained clinicians was made. Another excellent way in which physicians can learn about molecular biology as it applies to nutrition is through the clinical Nutrition Research Unit (CNRU) program. The NIH supports eight CNRUs--five funded by the National Institute of Diabetes and Digestive and Kidney Diseases and three funded by the National Cancer Institute. These CNRU8 provide support for long-term multidisciplinary programs of research in critical health problem areas, as well as provide an excellent environment for training new investigators.

INTRAMURAL NUTRITION RESEARCH

Question. Can you describe the intramural aspects of the NIH program as related to problems of nutrition. Specifically, are there activities at your institute that involve the clinical center and studies of human nutrition?

Answer. The major focus of NIH-supported nutrition research is extramural. The NIH intramural program is carried out on the Bethesda, Maryland, campus primarily at the Warren Grant Magnuson Clinical Center. Exceptions are the programs of the National Cancer Institute, the National Institute on Aging, and the National Institute of Environmental Health Sciences, which are conducted in laboratories off campus. The Nutrition Department of the clinical Center implements nutrition components of protocols generated by the various Institutes through collaborations between dietitians and clinical investigators. Implementation of protocol requirements includes provision of controlled nutrient intakes for various disease states and for drug-related studies. Test diets are provided, either as an integral part of a protocol or as a diagnostic procedure. Other research-related activities include obtaining anthropometric measurements to assess body composition, diet counseling for protocol-specific diets with subsequent determination of compliance, development and implementation of nutrition-education classes to support protocol requirements, development of questionnaires to assess dietary intake patterns, and provision of dietary regimens for studies requiring assessment of appetite in relation to specific drug therapies.

The intramural research activities supported by the NIDDK primarily include basic and clinical research on metabolism, endocrinology, hematology, digestive diseases, diabetes, and genetics. Studies in the Pima Indian population at the NIDDK Phoenix Epidemiology and Clinical Research Branch, supported at an annual rate of approximately $5 million, are aimed at unravelling the reasons behind the extraordinarily high prevalence of noninsulin-dependent diabetes mellitus (NIDDM) and obesity in this population. Studies among the Pima have revealed that the resting metabolic rate (RMR) is a familial trait, which may be linked to a single genetic defect, and that a low RMR may be predictive of body

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weight gain. Several years ago, NIDDK intramural researchers constructed a human respiratory chamber to permit the measurement of daily caloric expenditure and its components, in humans. with the RMR, a significant variability in the 24-hour metabolic rate also appears to be a familial trait. Continuing research on the genetic and metabolic factors related to NIDDM in the Pima may elucidate the disease process in other groups.

DIABETES INTRAMURAL RESEARCH

Question. I understand that the excellent laboratories in Phoenix, Arizona study problems of diabetes, and to a limited extent, problems of human obesity. Are there no similar activities on the Bethesda campus?

Answer. NIDDK Intramural researchers on the Bethesda campus of the NIH are examining how fat is metabolized by studying the genes, enzymes, and hormones involved in fat cell metabolism. They are studying the possible effects of hormone action on human fat distribution, which is reported to have major health effects, and have also determined a possible role for one enzyme in the wasting that occurs in tumor patients. In relation to obesity and diabetes, investigators are also focusing on glucose transporters-specialized proteins that convey sugar from outside the cell into its interior where it can be used to produce energy. In both diabetes and obesity, the number of such proteins stored by cells is markedly reduced.

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Question. Since there is only one NIH-funded Obesity Research Center, would it not be wise to consider creating more obesity centers either intra- or extramurally?

Answer. The existing Obesity Research Center funded by the National Institute of Diabetes and Digestive and Kidney Diseases is making valuable contributions to our scientific understanding of obesity. Additional centers would certainly strengthen our obesity program.

CLINICAL NUTRITION RESEARCH UNITS

Question. Are the clinical Nutrition Research Units now funded by NIH good vehicles for bringing physicians and medical students into high quality research in human nutrition?

Answer. The Clinical Nutrition Research Units (CNRUS) contribute enormously to the field of nutrition research, both in terms of promoting high quality research in clinical nutrition and in exposing young investigators to the importance of nutrition in health and disease. CNRUS are a bridging mechanism for basic and clinical research in the nutrition sciences. Advances in nutrition derive from many diverse scientific disciplines and clinical specialities. In order to transfer these scientific advances to physicians, other health professionals, and the public, a close interaction among the areas of research, health services, and education is essential. The CNRUS provide an optimal environment for this interactive exchange.

A large number of deficiency states, consequences of inborn errors of metabolism, and food-related diseases are better understood now, and may be treatable, or preventable. However, many unanswered questions remain on the relationship of diet to health and disease, particularly in cancer, other chronic diseases and aging. Locating CNRUs in medical school environments where they are associated with NIH-supported training programs in nutrition equips researchers to address these health issues effectively. This structure not only attracts promising scientists to the field but helps to establish nutrition as a discrete discipline in these institutions. The CNRUs build upon an established base of already funded research excellence in clinical nutrition research and make available core laboratories in areas such as metabolism and food intake to students, trainees, and investigators. CNRUs also provide start-up funding for pilot studies of new investigators, as well as broad educational programs for medical students, house staff, practicing physicians, and allied health personnel.

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For example, at one NIDDK-supported CNRU, a major theme is the nuritional management of very low birth weight infants. Until recently, very little information has been available regarding vitamin requirements during parenteral feeding of children. micromethods for analysis of specific levels of vitamins and nutrients have been developed and validated at this center. This advance has led directly to improved patient care and insights into other health implications for this at-risk population. A large study on diet and atherosclerosis is being carried out at another CNRU that examines the effect of different levels of fat content in the diet on cholesterol concentrations. These studies will help to show what level of decrease in fat content in the diet is important in lowering cholesterol and the risk of heart attack and stroke. As these few examples illustrate, CNRUS create a focus for nutrition research that would not exist otherwise.

NUTRITION RESEARCH PLANS

Question. Is there a formal research plan for dealing with the most pressing issues in clinical nutrition such as: what is the molecular defect underlying the genetic influence on human obesity; what are the physiologic effects of the widely recommended reduction in fat intake; are there any biochemical or other markers to determine the fat intake or intake of other nutrients that can be used in evaluating the efficacy of diet; dietary change; how important are infantile or early childhood nutritional practices on guiding nutritional behavior in adult life; are there suitable animal models or other methods under investigation by NIH to analyze the scientific basis for any potential relationship of early nutrition and later adult nutritional behavior and health?

Answer. The annual report of the NIH Nutrition Coordinating Committee summarizes the ongoing research activities and plans of all of the various NIH components that fund studies in this field. The questions you list are among those that the NIH institutes are seeking to answer through their collective efforts in nutrition science research.

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