Author
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Haymond, Morey |
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Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/1/1999 Publication Date: N/A Citation: Haymond,M.W. 1999. Nutritional and metabolic endpoints. Journal of Nutrition. 129(1S Suppl):273S-278S. Interpretive Summary: Protein wasting and malnutrition are a frequent consequence of a number of disease processes which health care providers manage on a daily basis. Appropriate management of these patients is imperative if we are going to improve the morbidity and mortality as well as their quality of life. Metabolic endpoints which night be utilized in the design of drug or therapeutic interventional trials of individuals with wasting conditions must be identified in order to provide meaningful and significant indications of success or failure of any interventions. With the development of numerous new therapies ranging from new categories of pharmaceutical agents to recombinant hormones to organ transplantation, the ultimate morbidity and mortality of a number of disease entities has dramatically changed. No single metabolic or nutritional endpoint exists which will be universally applicable under the wide spectrum of wasting disorders which should be considered for interventional management. Some of the nutritional and metabolic endpoints considered are: linear growth in children, immunocompentency, circulating proteins, nitrogen balance, amino acid kinetics, energy expenditure, and study design. Linear growth in children is a complex, dynamic, anabolic process that clearly involves energy and accretion of protein, calcium and other nutrients. Immunocompetence is a frequent co-morbidity factor in individuals with wasting and/or catabolic conditions. In situations which protein and energy malnutrition have occurred, the absolute lymphocyte concentration is found to be decreased and distributed to all categories of lymphocytes, not just T-cells. With plasma proteins, a number of circulating plasma protein concentrations are dramatically altered with injury, trauma, infection and protein wasting conditions. Nitrogen balance is the classical metabolic indicator of protein metabolism. This straightforward technique serves as the relative "gold standard" for many other nutritional indicators and endpoints. Amino acid kinetic studies involve the use of stable and radioactive isotope tracers of amino acids and has gained both popularity and utility. Utilizing these techniques collectively, it is possible to identify changes in amino acid and protein metabolism in response to an intervention within a period of hours. Indirect calorimetry is a method in which oxygen consumption and CO2 production are measured. Utilizing standard equations, the individual's metabolic rates can be estimated. Several points of caution should be considered in selecting or utilizing any single nutritional or metabolic endpoints. None of the metabolic indicators discussed provides a single or necessarily ideal endpoint in planning interventional management is wasting disorders. Manufacturers, regulators and investigators involved in the interventional management of chronic and acute wasting disorders must agree on the endpoints to be used and these must provide the most appropriate and valid information. Selection of nutritional and metabolic endpoints must be in part dependent on the disease process involved, the potential magnitude of the interventional effect, and must be utilized in the context of a carefully designed experimental protocol with well focused questions. Technical Abstract: None of the metabolic indicators which have been used to date provides a single or necessarily ideal endpoint for interventional management in wasting disorders. Some of these indicators may provide better endpoints for the acute rather than the chronic wasting conditions. In addition, it is imperative that more than one endpoint be selected to be assured that there is concordance in the findings. However, prior to the election of any endpoint measure, the investigators involved must be fully cognizant of the potential problems, developing strategies for the interpretation of the data is critical at the outset of any interventional management strategy. The manufacturers, the regulators and the investigators involved in the interventional management of chronic and acute wasting disorders must agree on the endpoints to be used and these endpoints must provide the most appropriate and valid information. Selection of nutritional and metabolic endpoints must be in part dependent on the disease process involved, the potential magnitude of the interventional effect and must be utilized in the context of a carefully designed experimental protocol with a well focused question(s). |
