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43 - Methods of measuring nutrient substrate utilization using stable isotopes

Published online by Cambridge University Press:  10 December 2009

Patti J. Thureen
Affiliation:
University of Colorado at Denver and Health Sciences Center
Agneta L. Sunehag
Affiliation:
Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX
Morey W. Haymond
Affiliation:
Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX
William W. Hay
Affiliation:
University of Colorado at Denver and Health Sciences Center
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Summary

Introduction

During fetal life a continuous supply of nutrients is transferred to the fetus via the placenta. Transplacental transported glucose is the major energy substrate for the fetus, which has glucose demands of 4–8 mg kg−1 min−1. The maternal–fetal transport of glucose occurs via passive diffusion facilitated by the glucose transporter system (specifically GLUT-1). Amino acids are transferred by active transport, and several classes of amino acid transporters have been identified in human placentas. Transplacental transfer of fatty acids is small. It is regulated by maternal fatty acid concentrations and is mediated by a number of different proteins. At birth, the transplacental supply of nutrients is abruptly interrupted and the newborn infant must first mobilize its own substrate stores and then rapidly adjust to enteral feedings to meet the metabolic needs.

Glucose is the primary substrate for brain metabolism, and the brain utilizes about 20 times more glucose than muscle and fat per gram tissue. Infants have a large brain to body weight ratio (12% in infants v. 2% in an adult). Thus, the glucose turnover rate on a per kg body weight basis in an infant is three times higher than that of an adult, ∼30 μmol kg−1 min−1 (∼6 mg kg−1 min−1) v. 11 μmol kg−1 min−1 (∼2 mg kg−1 min−1). As a result, ∼90% of total glucose utilization in an infant is by the brain.

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Publisher: Cambridge University Press
Print publication year: 2006

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References

Ogata, E. S.Carbohydrate metabolism in the fetus and neonate and altered neonatal glucoregulation. Pediatr. Clin. N. Am. 1986;33: 25–45.CrossRefGoogle ScholarPubMed
Aynsley-Green, A.Metabolic and endocrine interrelations in the human fetus and neonate. Am. J. Clin. Nutr. 1985;41 (Suppl. 2):399–417.CrossRefGoogle Scholar
Knipp, G. T., Audus, K. L., Soares, M. J.Nutrient transport across the placenta. Adv. Drug. Deliv. Rev. 1999;38:41–58.CrossRefGoogle ScholarPubMed
Bier, D. M., Leake, R. D., Haymond, M. W.et al.Measurement of “true” glucose production rates in infancy and childhood with 6,6-dideuteroglucose. Diabetes 1977;26:1016–23.CrossRefGoogle ScholarPubMed
Gruenwald, P., Minh, H. N.Evaluation of body and organ weights in perinatal pathology. I. Normal standards derived from autopsies. Am. J. Clin. Path. 1960;34:247–53.CrossRefGoogle ScholarPubMed
Shelley, H. J.Glycogen reserves and their changes at birth and in anoxia. Br. Med. Bull. 1961;17:137–43.CrossRefGoogle Scholar
Persson, B., Gentz, J.The pattern of blood lipids, glycerol and ketone bodies during the neonatal period, infancy and childhood. Acta Paediatr. Scand. 1966;55:353–62.CrossRefGoogle ScholarPubMed
Santerre, J., Karlberg, P.Respiratory quotient and metabolic rate in normal full-term and small-for-date newborn infants. Acta Paediatr. Scand. 1970;59:653–8.CrossRefGoogle Scholar
Cross, K. W., Tizard, J. P. M., Trythall, D. A. H.The gaseous metabolism of the newborn infant. Acta Paediatr. Scand. 1957;46:265–85.CrossRefGoogle ScholarPubMed
Bougnères, P. F., Karl, I. E., Hillman, L. S., Bier, D. M.Lipid transport in the human newborn. Palmitate and glycerol turnover and the contribution of glycerol to neonatal hepatic glucose output. J. Clin. Invest. 1982;70:262–70.CrossRefGoogle ScholarPubMed
Fjeld, C. R., Cole, F. S., Bier, D. M.Energy expenditure, lipolysis, and glucose production in preterm infants treated with theophylline. Pediatr. Res. 1992;32:693–8.CrossRefGoogle ScholarPubMed
Patel, D., Kalhan, S.Glycerol metabolism and triglyceride-fatty acid cycling in the newborn: effects of maternal diabetes and intrauterine growth retardation. Pediatr. Res. 1992;31:52–8.CrossRefGoogle Scholar
Sunehag, A., Gustafsson, J., Ewald, U.Glycerol carbon contributes to hepatic glucose production during the first eight hours in healthy, term infants. Acta Paediatr. Scand. 1996;85:1339–43.CrossRefGoogle Scholar
Sunehag, A., Ewald, U., Gustafsson, J.Extremely preterm infants (< 28 weeks) are capable of gluconeogenesis from glycerol on their first day of life. Pediatr. Res. 1996;40:553–7.CrossRefGoogle ScholarPubMed
Cahill, G. F. Jr, Herrera, M. G., Morgan, A. P.et al.Hormone-fuel interrelationships during fasting. J. Clin. Invest. 1966;45:1751–69.CrossRefGoogle ScholarPubMed
Bier, D. M.The use of stable isotopes in metabolic investigation. Baillieres Clin. Endocrinol. Metab. 1987;1:817–36.CrossRefGoogle ScholarPubMed
Bier, D. M. Mass spectrometry and stable isotopes. In Sadubray, J. M., Tada, K., eds. Inborn Metabolic Disease. Berlin: Springer Verlag; 1990:45–53.Google Scholar
Bougneres, P. F.Stable isotope tracers and the determination of fuel fluxes in newborn infants. Biol. Neonate 1987;52:87–96.CrossRefGoogle ScholarPubMed
Wolfe, R. R. Basic characteristics of isotope tracers. In Wolfe, R. R., ed. Radioactive and Stable Isotope Tracers in Biomedicine. Principles and Practice of Kinetic Analyses. New York, NY: Wiley-Liss Inc.; 1992:1–17.Google Scholar
Meer, K., Roef, M. J., Kulik, W., Jakobs, C.In vivo research with stable isotopes in biochemistry, nutrition and clinical medicine: an overview. Isotopes Environ. Health Stud. 1999;35:19–37.CrossRefGoogle ScholarPubMed
Argoud, G. M., Schade, D. S., Eaton, R. P.Underestimation of hepatic glucose production by radioactive and stable tracers. Am. J. Phys. 1987;252:E505–615.Google ScholarPubMed
Hachey, D. L., Parsons, W. R., McKay, S., Haymond, M. W.Quantitation of monosaccharide isotopic enrichment in physiologic fluids; by electron ionization or negative chemical ionization GC/MS using di-O-isopropylidene derivatives. Anal. Chem. 1999;71;4734–9.CrossRefGoogle ScholarPubMed
Patterson, B. W., Hachey, D. L., Cook, G. L., Amann, J. M., Klein, P. D.Incorporation of a stable isotopically labeled amino acid into multiple human apolipoproteins. J. Lipid Res. 1991;32:1063–72.Google ScholarPubMed
Lee, B., Yu, H., Jahoor, F.et al.In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorder of the urea cycle. Proc. Natl. Acad. Sci USA. 2000;5:8021–6.CrossRefGoogle Scholar
Hachey, D. L., Patterson, B. W., Reeds, P. J., Elsas, L. J.Isotopic determination of organic keto acid pentafluorobenzyl esters in biological fluids by negative chemical ionization gas chromatography/mass spectrometry. Analyt. Chem. 1991; 63:919–23.CrossRefGoogle ScholarPubMed
Wong, W. W., Lee, L. S., Klein, P. D.Deuterium and oxygen-18 measurements on microliter samples of urine, plasma, saliva and human milk. Am. J. Clin. Nutr. 1987;45:905–13.CrossRefGoogle ScholarPubMed
Tigas, S., Sunehag, A. L., Haymond, M. W.Impact of duration of infusion and choice of isotope label on isotope recycling in glucose homeostasis. Diabetes 2002:51:3170–5.CrossRefGoogle ScholarPubMed
Heath, D. F.Errors inherent in the primed infusion method for the measurement of the rate of glucose appearance in man when uptake is not forced by glucose or insulin infusion. Clin. Sci. 1990;79:201–3.CrossRefGoogle ScholarPubMed
Kalhan, S. C., Bier, D. M., Savin, S. M., Adam, P. A. J.Estimation of glucose turnover and 13C recycling in the human newborn by simultaneous [1-13C]glucose and [6,6-2H2]glucose tracers. J. Clin. Endocrinol. Metab. 1980;50:456–9.CrossRefGoogle ScholarPubMed
Bier, D. M., Arnold, K. J., Sherman, W. R.et al.In vivo measurement of glucose and alanine metabolism with stable isotope tracers. Diabetes 1977;26:1005–15.CrossRefGoogle Scholar
Steele, R., Wall, J. S., De-Bodo, R. C., Altzuler, N.Measurement of size and turnover rate of body glucose pool by the isotope dilution method. Am. J. Physiol. 1956;187:15–24.Google ScholarPubMed
Bodo, R. C., Steele, R., Altszuler, N., Dunn, A., Bishop, J. S.On hormonal regulation of carbohydrate metabolism; studies with C14 glucose. Recent Prog. Horm. Res. 1963;19:445–88.Google Scholar
Haymond, M. W., Sunehag, A. L.Controlling the sugar bowl: regulation of glucose homeostasis in children. Metab. Endocrinol. Clin. N. Am. 1999;28:663–94.CrossRefGoogle ScholarPubMed
Sunehag, A., Ewald, U., Larsson, A., Gustafsson, J.Attenuated hepatic glucose production but unimpaired lipolysis in newborn infants of mothers with diabetes. Pediatr. Res. 1997;42:492–97.CrossRefGoogle ScholarPubMed
Sunehag, A., Ewald, U., Larsson, A., Gustafsson, J.Glucose production rate in extremely immature neonates (< 28 w) studied by use of deuterated glucose. Pediatr. Res. 1993;33:97–100.CrossRefGoogle Scholar
Sunehag, A., Gustafsson, J., Ewald, U.Very immature infants (< 30 weeks) respond to glucose infusion with incomplete suppression of glucose production. Pediatr. Res. 1994;36:550–5.CrossRefGoogle Scholar
Tyrala, E. E., Chen, X., Boden, G.Glucose metabolism in the infant weighing less than 1100 grams. J. Pediatr. 1994;125:283–7.CrossRefGoogle ScholarPubMed
Frazer, T. E., Karl, I. E., Hillman, L. S., Bier, D. M.Direct measurement of gluconeogenesis from 2,3-13C2 alanine in the human neonate. Am. J. Physiol. 1981;240:E615–21.Google ScholarPubMed
Kalhan, S. C., Parimi, P., Beek, R.et al.Estimation of gluconeogenesis in newborn infants. Am. J. Physiol. Endocrinol. Metab. 2001;281:E991–7.CrossRefGoogle ScholarPubMed
Katz, J., Tayek, J. A.Gluconeogenesis and Cori cycle in 12, 20 and 40-hour fasted humans. Am. J. Physiol. 1998;275:E537–42.Google Scholar
Haymond, M. W., Sunehag, A. L.The reciprocal pool model for the measurement of gluconeogenesis using [U-13C]glucose. Am. J. Physiol. 2000;278:E140–45.Google Scholar
Hellerstein, M. K., Neese, R. A.Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers. Am. J. Physiol. 1992;263:E988–1001.Google ScholarPubMed
Neese, R. A., Schwartz, J-M., Faix, D.et al.Gluconeogenesis and intrahepatic triose phosphate flux in response to fasting or substrate loads. J. Biol. Chem. 1995;270:14452–66.CrossRefGoogle ScholarPubMed
Hellerstein, M. K., Neese, R. A., Linfoot, P.et al.Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. J. Clin. Invest. 1997;100:1305–19.CrossRefGoogle ScholarPubMed
Landau, B. R., Wahren, J., Chandramouli, V.et al.Use of 2H2O for estimating rates of gluconeogenesis. J. Clin. Invest. 1995;95:172–8.CrossRefGoogle ScholarPubMed
Kalhan, S. C., Trivedi, R., Singh, S.et al.A micromethod for the measurement of deuterium bound to carbon-6 of glucose to quantify gluconeogenesis in vivo. J. Mass Spec. 1995;30:1588–92.CrossRefGoogle Scholar
Landau, B. R., Wahren, J., Chandramouli, V.et al.Contributions of gluconeogenesis to glucose production in the fasted state. J. Clin. Invest. 1996;98:378–85.CrossRefGoogle ScholarPubMed
Fernandez, C. A., Des Rosiers, C., Previs, S. F., David, F., Brunengraber, H.Correction of 13C mass isotopomer distributions for natural stable isotope abundance. J. Mass Spec. 1996;31:255–62.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Muntz, J. A., Carrol, R. E.A method for converting glucose to fructose. J. Biol. Chem. 1960;235:1258–60.Google ScholarPubMed
Sunehag, A. L., Haymond, M. W., Schanler, R. J., Reeds, P. J., Bier, D. M.Gluconeogenesis in very low birth weight infants receiving total parenteral nutrition. Diabetes 1999;48:791–800.CrossRefGoogle ScholarPubMed
Sunehag, A. L., Clarke, L., Bier, D. M., Haymond, M. W.[U-13C]glucose MIDA provides accurate measures of gluconeogenesis, is easy to perform and requires only small blood sample volumes. Diabetes 2001;50 (Suppl. 2):A65.Google Scholar
Sunehag, A. L.Parenteral glycerol enhances gluconeogenesis in very premature infants. Pediatr. Res. 2003;53.CrossRefGoogle ScholarPubMed
Schwenk, W. F., Beaufrere, B., Haymond, M. W.Use of reciprocal pool specific activity to model leucine metabolism in humans. Am. J. Physiol. 1985;249:E646–50.Google Scholar
Waterlow, J. C., Garlick, P. J., Millward, D. J.Protein Turnover in Mammalian Tissue in the Whole Body. Amsterdam: Elsevier North Holland; 1978:301–25.Google Scholar
Poindexter, B. B., Karn, C. A., Ahlrichs, J. A.et al.Amino acids suppress proteolysis independent of insulin throughout the neonatal period. Am. J. Physiol. 1997;272:E592–9.Google ScholarPubMed
Denne, S. C., Karn, C. A., Ahlrichs, J. A.et al.Proteolysis and phenylalanine hydroxylation in response to parenteral nutrition in extremely premature and normal newborns. J. Clin. Invest. 1996;97:746–54.CrossRefGoogle ScholarPubMed
Rivera, A. Jr, Bell, E. F., Bier, D. M.Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life. Pediatr. Res. 1993;33:106–11.CrossRefGoogle ScholarPubMed
Pointdexter, B. B., Karn, C. A., Leitch, C. A., Liechty, E. A., Denne, S. C.Amino acids do not suppress proteolysis in premature neonates. Am. J. Physiol. Endocrinol. Metab. 2001;281:E472–8.CrossRefGoogle Scholar
Goudoever, J. B., Colen, T., Wattimena, J. L.et al.Immediate commencement of amino acid supplementation in preterm infants: effect on serum amino acid concentrations and protein kinetics on the first day of life. J. Pediatr. 1995;127:458–65.CrossRefGoogle ScholarPubMed
Denne, S. C., Karn, C. A., Liechty, E. A.Leucine kinetics after a brief fast and in response to feeding in premature infants. Am. J. Clin. Nutr. 1992;56:899–904.CrossRefGoogle ScholarPubMed
Beaufrere, B., Putet, G., Pachiaudi, C., Salle, B.Whole body protein turnover measured with 13C-leucine and energy expenditure in premature infants. Pediatr. Res. 1990;28:147–52.CrossRefGoogle Scholar
Denne, S. C., Karn, C. A., Wang, J., Liechty, J. A.Effect of intravenous glucose and lipid on proteolysis and glucose production in normal newborns. Am. J. Physiol. 1995;269:E361–7.Google ScholarPubMed
Hertz, D. E., Karn, C. A., Liu, Y. M., Liecthy, E. A., Denne, S. C.Intravenous glucose suppresses glucose production but not proteolysis in extremely premature newborns. J. Clin. Invest. 1993;92:1752–8.CrossRefGoogle Scholar
Thureen, P. J., Anderson, A. H., Baron, K. A.et al.Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition. Am. J. Clin. Nutr. 1998;68:1128–35.CrossRefGoogle ScholarPubMed
Liet, J. M., Piloquet, H., Marchini, J. S.et al.Leucine metabolism in preterm infants receiving parenteral nutrition with medium chain compared with long-chain triacylglycerol. Am. J. Clin. Nutr. 1999;69:539–43.CrossRefGoogle ScholarPubMed
Kalhan, S. C.Rates of urea synthesis in the human newborn. Effect of maternal diabetes and small size for gestational age. Pediatr. Res. 1993;34:801–4.CrossRefGoogle ScholarPubMed
Jequier, E., Acheson, K., Schutz, Y.Assessment of energy expenditure and fuel utilization in man. Ann. Rev. Nutr. 1987;7:187–208.CrossRefGoogle ScholarPubMed
Darmaun, D., Roig, J. C., Auestad, N., Sager, B. K., Neu, J.Glutamine metabolism in very low birthweight infants. Pediatr. Res. 1997;41:391–6.CrossRefGoogle Scholar
Amir, J., Reisner, S. H., Lapidot, A.Glycine turnover rates and pool sizes in neonates as determined by gas chromatography-mass spectrometry and nitrogen 15. Pediatr. Res. 1980;14:1238–44.CrossRefGoogle ScholarPubMed
Miller, R. G., Jahoor, F., Reeds, P. J., Heird, W. C., Jaksic, T.A new stable isotope tracer technique to assess human neonatal amino acid synthesis. J. Pediatr. Surg. 1995;30:1325–9.CrossRefGoogle ScholarPubMed
Miller, R. G., Jahoor, F., Jaksic, T.Decreased cysteine and proline synthesis in parenterally fed, premature infants. J. Pediatr. Surg. 1995;30:953–7.CrossRefGoogle ScholarPubMed
Bougneres, P. F., Lemmel, C., Ferre, P., Bier, D. M.Ketone body transportation in the human neonate and infant. J. Clin. Invest. 1986;77:42–8.CrossRefGoogle Scholar
Bougneres, P. F., Balasse, E. O., Ferre, P., Bier, D. M.Determination of ketone body kinetics using a D-(-)-3-hydroxy[4,4,4–2H3]butyrate tracer. J. Lipid Res. 1986;27:215–20.Google Scholar
Sauerwald, T. U., Hachey, D. L., Jensen, C. L.et al.Effect of dietary alpha-linolenic acid intake on incorporation of docosahexaenoic and arachidonic acids into plasma phospholipids of term infants. Lipids 1996;31 (Suppl.):S131–5.CrossRefGoogle ScholarPubMed
Carnielli, V. P., Wattimena, D. J., Luijendijk, I. H.et al.The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acid from linoleic and linolenic acids. Pediatr. Res. 1996;40:169–74.CrossRefGoogle ScholarPubMed
Sauerwald, T. U., Hachey, D. L., Jensen, C. L.et al.Intermediates in endogenous synthesis of C22:6 omega 3 and C20:4 omega 6 by term and preterm infants. Pediatr. Res. 1997;41:183–7.CrossRefGoogle ScholarPubMed
Bunt, J. E. H., Zimmerman, L. J., Wattimena, J. L.et al.Endogenous surfactant turnover in preterm infants measured with stable isotopes. Am. J. Respir. Crit. Care Med. 1998;157:810–14.CrossRefGoogle ScholarPubMed
Merchak, A., Patterson, B. W., Yarasheski, K. E., Hamvas, A.Use of stable isotope labeling technique and mass isotopomer distribution analysis of [13C]palmitate isolated from surfactant disaturated phospholipids to study surfactant in vivo kinetics in a premature infant. J. Mass Spectrom. 2000;35:734–8.3.0.CO;2-H>CrossRefGoogle Scholar
Torresin, M., Zimmerman, L. J., Cogo, P. E.et al.Exogenous surfactant kinetics in infant respiratory distress syndrome: a novel method with stable isotopes. Am. J. Respir. Crit. Care Med. 2000;161:1584–9.CrossRefGoogle ScholarPubMed
Lifson, N., Gordon, G. B., McClintock, R.Measurement of total carbon dioxide production by means of D2O18. J. Appl. Physiol. 1955;7:704–10.CrossRefGoogle ScholarPubMed
Schoeller, D. A.Energy expenditure from doubly labeled water: some fundamental considerations in humans. Am. J. Clin. Nutr. 1983;38:999–1005.CrossRefGoogle ScholarPubMed
Jones, R. H., Sonko, B. J., Miller, L. V., Thureen, P. J., Fennessey, P. V.Estimation of doubly labeled water energy expenditure with confidence intervals. Am. J. Physiol. Endocrinol. Metab. 2000;278:E383–9.CrossRefGoogle ScholarPubMed
Black, A. E., Prentice, A. M., Coward, W. A.Use of food quotients to predict respiratory quotients for the doubly labeled water method of measuring energy expenditure. Clin. Nutr. 1986;40C:381–91.Google Scholar
Lusk, G.The Elements of the Science of Nutrition. New York, NY: Johnson Reprint Corp., 1976 (original version 1928).Google Scholar
Schoeller, D. A., Webb, P.Five-day comparison of the doubly labeled water method with respiratory gas exchange. Am. J. Clin. Nutr. 1984;40:153–8.CrossRefGoogle ScholarPubMed
Roberts, B. R., Coward, W. A., Schlingenseipen, K.-H., Nohria, V., Lucas, A.Comparison of the doubly labeled water (2H218O) method with indirect calorimetry and a nutrient-balance study for simultaneous determination of energy expenditure, water intake, and metabolizable energy intake in preterm infants. Am. J. Clin. Nutr. 1986;44:315–22.CrossRefGoogle Scholar
Jensen, C., Butte, N. F., Wong, W. W., Moon, J. K.Determining energy expenditure in preterm infants: comparison of 2H218O method and indirect calorimetry. Am. J. Physiol. 1992;263:R685–92.Google Scholar
Leitch, C. A., Alrichs, J., Karn, C., Denne, S.Energy expenditure and energy intake during dexamethasone therapy for chronic lung disease. Pediatr. Res. 1999;46:109–13.CrossRefGoogle ScholarPubMed
Meer, K., Westerterp, K. R., Houwen, R. H. J.et al.Total energy expenditure in infants with bronchopulmonary dysplasia is associated with respiratory status. Eur. J. Pediatr. 1997;156: 299–304.CrossRefGoogle ScholarPubMed
Leitch, C. A., Karn, C. A., Peppard, R. J.et al.Increased energy expenditure in infants with cyanotic congenital heart disease. J. Pediatr. 1998;133:755–60.CrossRefGoogle ScholarPubMed

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