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Insulin resistance and glucose-induced thermogenesis in critical illness

Published online by Cambridge University Press:  05 March 2007

Gordon L. Carlson
Gordon L. Carlson*
Affiliation:
Department of Surgery, Hope Hospital, Salford M6 8HD, UK
*
Corresponding Author: Mr Gordon Carlson, fax +44 161 707 9708, email [email protected]
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Abstract

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Critical illness is associated with a marked increase in metabolic rate and progressive wasting, despite aggressive nutritional support. The metabolic events which are responsible for these phenomena are unclear, but are characterised by marked impairment of the anabolic effects of insulin on glucose metabolism and excessive activation of the sympathetic nervous system. It has been suggested that critical illness may be associated with impaired carbohydrate oxidation and a marked increase in the loss of heat energy associated with glucose administration (glucose-induced thermogenesis). This situation may result in impaired efficiency of nutrient assimilation. Studies employing combinations of nutrient infusions both at clinically-relevant rates and in association with euglycaemic hyperinsulinaemia have, however, demonstrated that nutrient-induced thermogenesis is unaffected in critical illness in human subjects, and that defective glucose utilization occurs as a consequence of impaired insulin-mediated glucose storage rather than oxidation. Although the cellular and molecular mechanisms underlying these changes are controversial, the recent validation of a human model of insulin resistance in critical illness should provide a means of studying this response in future, and allow the identification of therapeutic targets. This information should increase the efficacy of nutritional support in some of our most seriously-ill patients.

Keywords

Critical illnessInsulin resistanceGlucose-induced thermogenesisNutritional support
Type
Sir David Cuthbertson Medal Lecture
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 3 , August 2001 , pp. 381 - 388
Copyright
Copyright © The Nutrition Society 2001

References

Acheson, KJ, Jequier, E & Wahren, J (1983) Influence of beta adrenergic blockade on glucose-induced thermogenesis. Journal of Clinical Investigation 72, 981–986.CrossRefGoogle ScholarPubMed
Acheson, KJ, Ravussin, E, Wahren, J & Jéquier, E (1984) Thermic effect of glucose in man. Obligatory and facultative thermogenesis. Journal of Clinical Investigation 73, 1572–1580.CrossRefGoogle Scholar
Agwunobi, AO, Reid, C, Maycock, P, Little, RA & Carlson, GL (2000) Insulin resistance and substrate utilization in human endotoxaemia. Journal of Clinical Endocrinology and Metabolism 85, 3770–3778.CrossRefGoogle Scholar
Allard, JP, Jeejeebhoy, KN, Whitwell, J, Pashutinski, L & Peters, WJ (1988) Factors influencing energy expenditure in patients with burns. Journal of Trauma 28, 199–202.CrossRefGoogle ScholarPubMed
Arnold, J, Leinhardt, D, Carlson, G, Gray, P, Little, RA & Irving, MH (1992) Thermogenic and hormonal responses to amino acid infusion in septic humans. American Journal of Physiology 263, E129–E135.Google ScholarPubMed
Arnold, J, Shipley, K, Scott, NA, Little, RA & Irving, MH (1989) Thermic effect of parenteral nutrition in septic and non-septic individuals. American Journal of Clinical Nutrition 53, 853–863.CrossRefGoogle Scholar
Arnold, J, Shipley, KA, Scott, NA, Little, RA & Irving, MH (1991) Lipid infusion increases oxygen consumption similarly in septic and nonseptic patients. American Journal of Clinical Nutrition 53, 143–148.CrossRefGoogle ScholarPubMed
Askanazi, J, Carpentier, YA, Elwyn, DH, Nordenstrom, J, Jeevanandam, M, Rosenbaum, SH, Gump, FE & Kinney, JM (1980) Influence of total parenteral nutrition on fuel utilization in injury and sepsis. Annals of Surgery 291, 40–46.CrossRefGoogle Scholar
Barton, RN (1987) The neuroendocrinology of physical injury. Clinical Endocrinology and Metabolism 1, 355–374.Google ScholarPubMed
Bedard, S, Marcotte, B & Marette, A (1997) Cytokines modulate glucose transport in skeletal muscle by inducing the expression of inducible nitric oxide synthase. Biochemical Journal 325, 487–493.CrossRefGoogle ScholarPubMed
Begum, N & Ragolia, L (1996) Effect of tumor necrosis factor-alpha on insulin action in cultured rat skeletal muscle cells. Endocrinology 137, 2441–2446.CrossRefGoogle ScholarPubMed
Benedict, FG & Carpenter, TM (1918) Food ingestion and energy transformations with special reference to the stimulating effects of nutrients. Carnegie Institute of Washington 355–382.Google Scholar
Bessey, PQ, Watters, JM, Aoki, TT & Wilmore, DW (1984) Combined hormonal infusion simulates the metabolic response to injury. Annals of Surgery 200, 264–281.CrossRefGoogle ScholarPubMed
Bjorntorp, P & Sjostrom, L (1978) Carbohydrate storage in man: speculations and some quantitative considerations. Metabolism 27, 1853–1865.CrossRefGoogle ScholarPubMed
Bornstein, SR, Licinio, J, Tauchnitz, R, Engelmann, L, Negrao, AB, Gold, P & Chrousos, GP (1998a) Plasma leptin levels are increased in survivors of acute sepsis: Associated loss of diurnal rhythm in cortisol and leptin secretion. Journal of Clinical Endocrinology and Metabolism 83, 280–283.CrossRefGoogle ScholarPubMed
Bornstein, SR, Preas, HL, Chrousos, GP & Suffredini, AF (1998b) Circulating leptin levels during acute experimental endotoxemia and antiinflammatory therapy in humans. Journal of Infectious Diseases 178, 887–890.CrossRefGoogle ScholarPubMed
Carlson, GL (1998) Nutrient induced thermogenesis. In Baillière's Clinical Endocrinology and Metabolism: Energy Metabolism in Trauma, pp. 603–615 [Little, RA and Werrneman, J, editors]. London: Baillière-Tindall.Google Scholar
Carlson, GL, Gray, P, Arnold, J, Little, RA & Irving, MH (1994) Thermogenic, hormonal and metabolic effects of a TPN mixture. Influence of glucose and amino acids. American Journal of Physiology 266, E845–E851.Google ScholarPubMed
Carlson, GL, Gray, P, Arnold, J, Little, RA & Irving, MH (1997) Thermogenic, hormonal and metabolic effects of intravenous glucose infusion in human sepsis. British Journal of Surgery 84, 1454–1459.Google ScholarPubMed
Carlson, GL & Little, RA (1992) The pathophysiology and pattern of the hormonal response to severe sepsis. In Endocrine Consequences of Critical Illness, pp. 57–69 [Boles, JM, editor]. Paris: Arnette.Google Scholar
Carlson, GL & Little, RA (1994) Insulin resistance and tissue fuels. In Organ Metabolism and Nutrition: Ideas for Critical Care, pp. 49–69 [Kinney, JM, editor]. New York: Raven Press.Google Scholar
Carlson, GL, Saeed, M, Little, RA & Irving, MH (1999) Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis. American Journal of Physiology 276, E658–E662.Google ScholarPubMed
Carpenter, TM & Fox, EL (1930) The gaseous exchange of the human subject III. As affected by small quantities of levulose. Journal of Nutrition ii, 389–408.CrossRefGoogle Scholar
Catania, RA, Schwacha, MG, Cioffi, WG, Bland, KI & Chaudry, IH (1999) Does uninjured skin release proinflammatory cytokines following trauma and hemorrhage? Archives of Surgery 134, 368–374.CrossRefGoogle Scholar
Christin, L, Nach, C-A, Vernet, O, Ravussin, E, Jéquier, E & Acheson, K (1986) Insulin – its role in the thermic effect of glucose. Journal of Clinical Investigation 77, 1747–1755.CrossRefGoogle ScholarPubMed
Cohen, B, Novick, D & Rubinstein, M (1996) Modulation of insulin activities by leptin. Science 274, 1185–1188.CrossRefGoogle ScholarPubMed
DeFronzo, R, Thorin, D, Felber, J, Simonson, D, Thiebaud, D, Jequier, E & Golay, A (1984) Effect of beta and alpha adrenergic blockade on glucose-induced thermogenesis in man. Journal of Clinical Investigation 73, 633–639.CrossRefGoogle ScholarPubMed
Elwyn, DH, Kinney, JM, Jeevanandam, M, Gump, FE & Broell, JR (1978) Influence of increasing carbohydrate intake on glucose kinetics in injured patients. Annals of Surgery 190, 117–126.CrossRefGoogle Scholar
Evans, EI & Butterfield, WJH (1951) The stress response in the severely burned. Annals of Surgery 134, 588–613.CrossRefGoogle ScholarPubMed
Fan, J, Li, YH, Wojnar, MM & Lang, CH (1996) Endotoxin-induced alterations in insulin-stimulated phosphorylation of insulin receptor, IRS-1 and MAP kinase in skeletal muscle. Shock 6, 164–170.CrossRefGoogle ScholarPubMed
Ferrannini, E, Smith, JD, Cobelli, C, Toffolo, G, Pilo, A & DeFronzo, RA (1985) Effect of insulin on the distribution and disposition of glucose in man. Journal of Clinical Investigation 76, 357–364.CrossRefGoogle ScholarPubMed
Fischer, P (1862) Du diabete consecutif aux traumatismes (Diabetes following traumas). Archives Generale de Medecine 20, 413–443.Google Scholar
Flatt, JP (1977) The biochemistry of energy expenditure. In Recent Advances in Obesity Research, pp. 211–228 [Bray, GA, editor]. Washington, DC: Newman.Google Scholar
Furnsinn, C, Neschen, S, Wagner, O, Roden, M, Bisschop, M & Waldhausl, W (1997) Acute and chronic exposure to tumor necrosis factor-alpha fails to affect insulin-stimulated glucose metabolism of isolated rat soleus muscle. Endocrinology 138, 2674–2679.CrossRefGoogle ScholarPubMed
Gelfand, RA, Matthews, DE, Bier, DM & Sherwin, RS (1984) Role of counterregulatory hormones in the catabolic response to stress. Journal of Clinical Investigation 74, 2238–2248.CrossRefGoogle ScholarPubMed
Giovannini, I, Chiarla, C, Boldrini, G, Castiglioni, G & Castagneto, M (1988) Calorimetric response to amino acid infusion in sepsis and critical illness. Critical Care Medicine 16, 667–670.CrossRefGoogle ScholarPubMed
Green, CJ, Campbell, IT, O'Sullivan, E, Underhill, S, McLaren, DPM, Hipkin, LJ, MacDonald, IA & Russell, J (1995) Septic patients in multiple organ failure can oxidize infused glucose but non-oxidative disposal (storage) is impaired. Clinical Science 89, 601–609.CrossRefGoogle ScholarPubMed
Grunfeld, C, Zhao, C, Fuller, J, Pollock, A, Moser, A, Friedman, J & Feingold, K (1996) Endotoxin and cytokines induce expression of leptin the ob gene product in hamsters. Journal of Clinical Investigation 97, 2152–2157.CrossRefGoogle ScholarPubMed
Howard, JM (1955) Studies of the absorption and metabolism of glucose following injury. Annals of Surgery 141, 321.CrossRefGoogle ScholarPubMed
Krebs, HA (1964) The metabolic fate of amino acids. In Mammalian Protein Metabolism, pp. 125–176 [Munro, HN and Allison, JB, editors]. New York and London: Academic Press.CrossRefGoogle Scholar
Lang, CH, Dobrescu, C & Bagby, GJ (1992) Tumor necrosis factor impairs insulin action on peripheral glucose disposal and hepatic glucose output. Endocrinology 130, 43–52.CrossRefGoogle ScholarPubMed
Lavoisier, AL & LaPlace, P (1784) Memoire sur la chaleur (Memoir on heat). Histoires Academie Royale Science 355–408.Google Scholar
Leinhardt, DJ, Arnold, J, Shipley, KA, Mughal, MM, Little, RA & Irving, MH (1993) Plasma NE concentrations do not accurately reflect sympathetic nervous system activity in human sepsis. American Journal of Physiology 265, E284–E288.Google Scholar
Liu, YL, Emilsson, V & Cawthorne, MA (1997) Leptin inhibits glycogen synthesis in the isolated soleus muscle of obese ob/ob mice. FEBS Letters 411, 351–355.CrossRefGoogle ScholarPubMed
Lusk, G (1912) Animal calorimetry. The influence of the ingestion of amino acids upon metabolism. Journal of Biological Chemistry XIII, 155–183.CrossRefGoogle Scholar
Lusk, G (1922) The specific dynamic action of various food factors. Medicine 1, 311–354.CrossRefGoogle Scholar
Lusk, G (1931) The specific dynamic action. Journal of Nutrition iii, 519–530.Google Scholar
McCall, JL, Tuckey, JA & Parry, BR (1992) Serum tumor necrosis factor alpha and insulin resistance in gastrointestinal cancer. British Journal of Surgery 79, 1361–1363.CrossRefGoogle ScholarPubMed
Magnus-Levy, A (1894) Über die Grosse des respiratorischen Gaswechsels unter dem einfluss der nahrungsaufnahme (On the extent of respiratory gaseous exchange in relation to food intake). Pflugers Archiv 46, 1–126.Google Scholar
Moan, A, Hoieggen, A, Nordby, G, Birkeland, K, Eide, I & Kjeldsen, SE (1995) The glucose clamp procedure activates the sympathetic nervous system even in the absence of hyperinsulinemia. Journal of Clinical Endocrinology and Metabolism 80, 3151–3154.Google ScholarPubMed
Molina, PE, Malek, S, Lang, CH, Qian, L, Naukam, R & Abumrad, NN (1997) Early organ-specific hemorrhage-induced increases in tissue cytokine content: Associated neurohormonal and opioid alterations. Neuroimmunomodulation 4, 28–36.CrossRefGoogle ScholarPubMed
Moshyedi, AK, Josephs, MD, Abdalla, EK, Mackay, SL, Edwards, CK III, Copeland, EM III & Moldawer, LL (1998) Increased leptin expression in mice with bacterial peritonitis is partially regulated by tumor necrosis factor alpha. Infection and Immunity 66, 1800–1802.CrossRefGoogle ScholarPubMed
Newsholme, EA & Crabtree, B (1976) Substrate cycles in metabolic regulation and in heat generation. Biochemical Society Symposia 41, 61–109.Google Scholar
Ng, LL & Hockaday, TD (1989) The effect of environmental temperature on prandial changes in leucocyte sodium transport. British Journal of Nutrition 62, 639–645.CrossRefGoogle ScholarPubMed
Noguchi, Y, Yoshikawa, T, Marat, D, Doi, C, Makino, T, Fukuzawa, K, Tsuburaya, A, Satoh, S, Ito, T & Mitsuse, S (1998) Insulin resistance in cancer patients is associated with enhanced tumor necrosis factor alpha expression in skeletal muscle. Biochemical and Biophysical Research Communications 253, 887–892.CrossRefGoogle ScholarPubMed
Nordenström, JM, Jeevanandam, M, Elwyn, DH, Carpentier, YA, Askanazi, J, Arnold, R & Kinney, JM (1981) Increasing glucose intake during total parenteral nutrition increases norepinephrine in trauma and sepsis. Clinical Physiology 1, 525–534.CrossRefGoogle ScholarPubMed
Randle, PJ, Garland, PB, Hales, CN & Newsholme, EA (1963) The glucose fatty acid cycle, its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet i, 787–788.Google Scholar
Ravussin, E & Bogardus, C (1982) Thermogenic response to insulin and glucose infusions in man: a model to evaluate the different components of the thermic effect of carbohydrate. Life Science 31, 2011–2018.CrossRefGoogle Scholar
Robertson, RP & Porte, D Jr (1974) Plasma catecholamine responses to intravenous glucose in normal man. Journal of Clinical Endocrinology and Metabolism 39, 403–405.CrossRefGoogle ScholarPubMed
Rubner, M (1902) Die Gesetze die Energieverbrauchs bei der Ernahrung (The laws of energy consumption with nutrition). Leipzig and Vienna: Rubner.Google Scholar
Saeed, M & Carlson, GL (1995) Substrate utilisation after injury. International Journal of Orthopaedic Trauma 5, 152–157.Google Scholar
Saeed, M, Carlson, GL, Little, RA & Irving, MH (1999) Selective impairment of glucose storage in human sepsis. British Journal of Surgery 86, 813–821.CrossRefGoogle ScholarPubMed
Segal, KR, Landt, M & Klein, S (1996) Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 45, 988–991.CrossRefGoogle ScholarPubMed
Shulman, RG, Bloch, G & Rothman, DL (1995) In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis. Proceedings of the National Academy of Sciences USA 92, 8535–8542.CrossRefGoogle ScholarPubMed
Smith, E (1859) Experiments on respiration-second communication. On the action of foods upon the respiration during the primary processes of digestion. Philosophical Transactions of the Royal Society 149, 715–742.Google Scholar
Stoner, HB, Little, RA, Frayn, KN, Elebute, EA, Tresadern, J & Gross, E (1983) The effect of sepsis upon the oxidation of carbohydrate and fat. British Journal of Surgery 70, 32–35.CrossRefGoogle ScholarPubMed
Stratton, RJ, Dewit, O, Crowe, E, Jennings, G, Villar, RN & Elia, M (1997) Plasma leptin, energy intake and hunger following total hip replacement surgery. Clinical Science 93, 113–117.CrossRefGoogle ScholarPubMed
Thiebaud, D, Schutz, Y, Acheson, K, Jacot, E, DeFronzo, R, Felber, J-P, & Jequier, E (1983) Energy cost of glucose storage in human subjects during glucose-insulin infusions. American Journal of Physiology 244, E216–E221.Google ScholarPubMed
Thorell, A, Efendic, S, Gutniak, M, Haggmark, T & Ljungqvist, O (1994) Insulin resistance after abdominal surgery. British Journal of Surgery 81, 59–63.CrossRefGoogle ScholarPubMed
Uysal, KT, Wiesbrock, SM, Marino, MW & Hotamisligil, GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389, 610–4.CrossRefGoogle ScholarPubMed
Vary, TC, Drnevich, D, Jurasinski, C & Brennan, WA (1995) Mechanisms regulating skeletal muscle glucose metabolism in sepsis. Shock 3, 403–410.Google ScholarPubMed
Virkamaki, A, Puhakainen, I, Koivisto, VA, Vuorinen-Markkola, H & Yki-Jarvinen, H (1992) Mechanisms of hepatic and peripheral insulin resistance during acute infections in humans. Journal of Clinical Endocrinology and Metabolism 74, 673–679.Google ScholarPubMed
Virkamaki, A & Yki-Jarvinen, H (1994) Mechanisms of insulin resistance during acute endotoxaemia. Endocrinology 134, 2072–2078.CrossRefGoogle Scholar
Welle, S, Lilavivat, U & Campbell, RG (1981) Thermic effect of feeding in man: increased plasma norepinephrine levels following glucose but not protein or fat consumption. Metabolism 30, 953–958.CrossRefGoogle ScholarPubMed
White, RH, Frayn, KN, Little, RA, Threlfall, CJ, Stoner, HB & Irving, MH (1987) Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycaemic glucose clamp technique. Journal of Parenteral and Enteral Nutrition 11, 345–353.CrossRefGoogle ScholarPubMed
Winkler, G, Salamon, F, Salamon, D, Speer, G, Simon, K & Cseh, K (1998) Elevated serum tumour necrosis factor alpha levels can contribute to the insulin resistance in Type II (non- insulin-dependent) diabetes and in obesity. Diabetologia 41, 860–861.Google Scholar
Wolfe, RR, Jahoor, F, Herndon, D & Miyoshi, H (1991) Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion. Surgery 110, 54–67.Google Scholar