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Hyperglycaemia and pulmonary infection

Published online by Cambridge University Press:  07 March 2007

Emma H. Baker ,
David M. Wood ,
Amanda L. Brennan ,
Nicholas Clark ,
Deborah L. Baines  and
Barbara J. Philips
Emma H. Baker*
Affiliation:
Glucose and Pulmonary Infection Group, Cardiac and Vascular Sciences (Respiratory), St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
David M. Wood
Affiliation:
Glucose and Pulmonary Infection Group, Cardiac and Vascular Sciences (Respiratory), St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
Amanda L. Brennan
Affiliation:
Glucose and Pulmonary Infection Group, Cardiac and Vascular Sciences (Respiratory), St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
Nicholas Clark
Affiliation:
Glucose and Pulmonary Infection Group, Cardiac and Vascular Sciences (Respiratory), St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
Deborah L. Baines
Affiliation:
Glucose and Pulmonary Infection Group, Cardiac and Vascular Sciences (Respiratory), St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
Barbara J. Philips
Affiliation:
Glucose and Pulmonary Infection Group, Cardiac and Vascular Sciences (Respiratory), St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
*
*Corresponding author: Dr Emma Baker, fax: +44 20 8725 5955; email ebaker@sgul.ac.uk
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Abstract

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Pathophysiological stress from acute illness causes metabolic disturbance, including altered hepatic glucose metabolism, increased peripheral insulin resistance and hyperglycaemia. Acute hyperglycaemia is associated with increased morbidity and mortality in patients in intensive care units and patients with acute respiratory disease. The present review will consider mechanisms underlying this association. In normal lungs the glucose concentration of airway secretions is approximately 10-fold lower than that of plasma. Low airway glucose concentrations are maintained against a concentration gradient by active glucose transport. Airway glucose concentrations become elevated if normal homeostasis is disrupted by a rise in blood glucose concentrations or inflammation of the airway epithelium. Elevated airway glucose concentrations are associated with and precede increased isolation of respiratory pathogens, particularly methicillin-resistant Staphylococcus aureus, from bronchial aspirates of patients intubated on intensive care. Markers of elevated airway glucose are associated with similar patterns of respiratory infection in patients admitted with acute exacerbations of chronic obstructive pulmonary disease. Glucose at airway concentrations stimulates the growth of respiratory pathogens, over and above the effect of other nutrients. Elevated airway glucose concentrations may also worsen respiratory disease by promoting local inflammation. Hyperglycaemia may thus promote pulmonary infection, at least in part, by an effect on airway glucose concentrations. Therapeutic options, including systemic control of blood glucose and local manipulation of airway glucose homeostasis, will be considered.

Keywords

HyperglycaemiaStressInfectionLung diseasesInsulin
Type
BAPEN Symposium 1 on ‘Nutritional support in children and adolescents’
Information
Proceedings of the Nutrition Society , Volume 65 , Issue 3 , August 2006 , pp. 227 - 235
Copyright
Copyright © The Nutrition Society 2006

References

Adewoye, LO & Worobec, EA (2000) Identification and characterisation of the gltK gene encoding a membrane-associated glucose transport protein of Pseudomonas aeruginosa. Gene 253 323–330.CrossRefGoogle ScholarPubMed
Baker, EH, Janaway, CH, Philips, BJ, Brennan, AL, Baines, DL, Wood, DM & Jones, PW (2006) Hyperglycaemia is associated with poor outcomes in people admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax 61 284–289.CrossRefGoogle ScholarPubMed
Barker, PM, Boyd, CA, Ramsden, CA, Strang, LB & Walters, DV (1989) Pulmonary glucose transport in the fetal sheep. Journal of Physiology 409 15–27.Google Scholar
Borst, SE, Lee, Y, Conover, CF, Shek, EW & Bagby, GJ (2004) Neutralization of tumor necrosis factor-alpha reverses insulin resistance in skeletal muscle but not adipose tissue. American Journal of Physiology 287 E934–E938.Google Scholar
Brennan, AL, Gyi, KM, Clark, N, Fisher, DA, Wood, DM, Baines, DL, Philips, BJ, Geddes, DM, Hodson, ME & Baker, EH (2006) Detection of elevated glucose concentrations in lower airway secretions from people with cystic fibrosis. Thorax 60, (sII) ii93.Google Scholar
Brennan, AL, Johnson, J, Holliman, R, Philips, BJ & Baker, EH (2004) Glucose at concentrations found in airway secretions increases the growth of Staphylococcus aureus. American Journal of Respiratory and Critical Care Medicine 169, A371.Google Scholar
Capes, SE, Hunt, D, Malmberg, K & Gerstein, HC (2000) Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 355 773–778.Google Scholar
Capes, SE, Hunt, D, Malmberg, K, Pathak, P & Gerstein, HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 32 2426–2432.CrossRefGoogle ScholarPubMed
Chance, DL & Mawhinney, TP (2000) Carbohydrate sulfation effects on growth of Pseudomonas aeruginosa. Microbiology 146 1717–1725.CrossRefGoogle ScholarPubMed
Chen, SS, Donmoyer, C, Zhang, Y, Hande, SA, Lacy, DB & McGuinness, OP (2000) Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism. Journal of Parenteral and Enteral Nutrition 24 255–260.CrossRefGoogle ScholarPubMed
Chhibber, VL, Soriano, C & Tayek, JA (2000) Effects of low-dose and high-dose glucagon on glucose production and gluconeogenesis in humans. Metabolism 48 39–46.CrossRefGoogle Scholar
Chu, CA, Sindelar, DK, Neal, DW, Allen, EJ, Donahue, EP & Cherrington, AD (1997) Comparison of the direct and indirect effects of epinephrine on hepatic glucose production. Journal of Clinical Investigation 99 1044–1056.CrossRefGoogle ScholarPubMed
Chu, CA, Sindelar, DK, Neal, DW & Cherrington, AD (1996) Direct effects of catecholamines on hepatic glucose production in conscious dog are due to glycogenolysis. American Journal of Physiology 271 E127–E137.Google Scholar
Clark, N, Fisher, DA, Wood, DM, Brennan, AL, Philips, BJ, Baines, DL, Grimble, G & Baker, EH (2004) Developing methods for determining dilution factor and measuring low glucose concentrations in exhaled breath condensate. Thorax 59, Suppl. II, ii46.Google Scholar
Clark, N, Wood, DM, Fisher, DA, Ruffles, T, Brennan, AL, Philips, BJ, Baines, DL & Baker, EH (2006) Effect of changes in blood glucose concentration on glucose concentrations of lower airway secretions sampled by exhaled breath condensate. Thorax 60 (sII) ii87.Google Scholar
Dandona, P, Mohanty, P, Chaudhuri, A, Garg, R & Aljada, A (2005) Insulin infusion in acute illness. Journal of Clinical Investigation 115 2069–2072.CrossRefGoogle ScholarPubMed
Devaskar, SU & de Mello, DE (1996) Cell-specific localization of glucose transporter proteins in mammalian lung. Journal of Clinical Endocrinology and Metabolism 81 4373–4378.Google ScholarPubMed
Esposito, K, Nappo, F, Marfella, R, Giugliano, G, Giugliano, F, Ciotola, M, Quagliaro, L, Ceriello, A & Guigliano, D (2002) Inflammatory cytokine concentrations are acutely increased by hyperglycaemia in humans: role of oxidative stress. Circulation 106 2067–2072.CrossRefGoogle ScholarPubMed
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 25 Suppl. S5–S20Google Scholar
Exton, JH, Miller, TB, Harper, SC & Park, CR (1976) Carbohydrate metabolism in perfused livers of adrenalectomized and steroid-replaced rats. American Journal of Physiology 230 163–170.CrossRefGoogle ScholarPubMed
Finney, SJ, Zekveld, C, Elia, A & Evans, TW (2003) Glucose control and mortality in critically ill patients. Journal of the American Medical Association 290 2041–2047.CrossRefGoogle ScholarPubMed
Geerlings, SE & Hoepelman, AI (1999) Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunology and Medical Microbiology 26 259–265.CrossRefGoogle ScholarPubMed
Gustavson, SM, Chu, CA, Nishizawa, M, Farmer, B, Neal, D, Yang, Y, Donahue, EP, Flakoll, P & Cherrington, AD (2003) Interaction of glucagon and epinephrine in the control of hepatic glucose production in the conscious dog. American Journal of Physiology 284 E695–E707.Google ScholarPubMed
Hill Golden, S, Peart-Vigilance, C, Kao, WH & Brancati, FL (1999) Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care 22 1408–1414.CrossRefGoogle Scholar
Hotamisligil, GS (1999) Mechanisms of TNF-alpha-induced insulin resistance. Experimental and Clinical Endocrinology & Diabetes 107 119–125.Google Scholar
Icard, P & Saumon, G (1999) Alveolar sodium and liquid transport in mice. American Journal of Physiology 277 L1232–L1238.Google ScholarPubMed
Ishikawa, N, Oguri, T, Isobe, T, Fujitaka, K & Kohno, N (2001) SGLT gene expression in primary lung cancers and their metastatic lesions. Japanese Journal of Cancer Research 92 874–879.Google Scholar
Ito, T, Noguchi, Y, Satoh, S, Hayashi, H, Inayama, Y & Kitamura, H (1998) Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage. Modern Pathology 11 437–443.Google ScholarPubMed
Khair, OA, Devalia, JL, Abdelaziz, MM, Sapsford, RJ, Tarraf, H & Davies, RJ (1994) Effect of haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF-alpha and expression of ICAM-1 in cultured human bronchial epithelial cells. The European Respiration Journal 7 2109–2116.Google Scholar
Khaodhiar, L, McCowen, K & Bistrian, B (1999) Perioperative hyperglycemia, infection or risk. Current Opinion in Clinical Nutrition and Metabolic Care 2 79–82.Google Scholar
Kievit, TR, Gillis, R, Marx, S, Brown, C & Iglewski, BH (2001) Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Applied and Environmental Microbiology 67 1865–1873.CrossRefGoogle ScholarPubMed
Kim, HJ, Higashimori, T, Park, SY, Choi, H, Dong, J, Kim, YJ, Noh, HL, Cho, YR, Cline, G, Kim, YB & Kim, JK (2004) Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53 1060–1067.CrossRefGoogle ScholarPubMed
Krinsley, J & Grissler, B (2005) Intensive glycemic management in critically ill patients. Joint Commission Journal on Quality and Patient Safety 31 308–312.Google Scholar
Lanng, S, Thorsteinsson, B, Nerup, J & Koch, C (1994) Diabetes mellitus in cystic fibrosis: effect of insulin on lung function and infections. Acta Paediatrica 83 849–853.CrossRefGoogle ScholarPubMed
Lecavalier, L, Bolli, G & Gerich, J (1990) Glucagon-cortisol interactions on glucose turnover and lactate gluconeogenesis in normal humans. American Journal of Physiology 258 E569–E575.Google Scholar
McAlister, FA, Majumdar, SR, Blitz, S, Rowe, BH, Romney, J & Marrie, TJ (2005) The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care 28 810–815.Google Scholar
McGuinness, OP (2005) Defective glucose homeostasis during infection. Annual Review of Nutrition 25 9–35.CrossRefGoogle ScholarPubMed
McGuinness, OP, Burgin, K, Moran, C, Bracy, D & Cherrington, AD (1994a) Role of glucagon in the metabolic response to stress hormone infusion in the conscious dog. American Journal of Physiology 266 E438–E447.Google ScholarPubMed
McGuinness, OP, Donmoyer, C, Ejiofor, J, McElligott, S & Lacy, DB (1998) Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection. American Journal of Physiology 275 E763–E769.Google Scholar
McGuinness, OP, Jacobs, J, Moran, C & Lacey, DB (1995) Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog. American Journal of Physiology 269 E199–E207.Google Scholar
McGuinness, OP, Murrell, S, Moran, C, Bracy, D & Cherrington, AD (1994b) The effect of acute glucagon removal on the metabolic response to stress hormone infusion in the conscious dog. Metabolism 43 1310–1317.Google Scholar
McGuinness, OP, Snowden, RT, Moran, C, Neal, DW, Fujiwara, T & Cherrington, AD (1999) Impact of acute epinephrine removal on hepatic glucose metabolism during stress hormone infusion. Metabolism 48 910–914.CrossRefGoogle ScholarPubMed
Ma, J-F, Phibbs, PV & Hassett, DJ (1997) Glucose stimulates alginate production and algD transcription in Pseudomonas aeruginosa. FEMS Microbiology Letters 148 217–221.CrossRefGoogle ScholarPubMed
Magnusson, I, Rothman, DL, Gerard, DP, Katz, LD & Shulman, GI (1995) Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration. Diabetes 44 185–189.Google Scholar
Malmberg, K, Ryden, L, Efendic, S, Herlitz, J, Nicol, P, Waldenstrom, A, Wedel, H & Welin, L (1995) Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI Study): effects on mortality at 1 year. Journal of the American College of Cardiology 26 57–65.Google Scholar
Mao, Y, Ling, PR, Fitzgibbons, TP, McCowen, KC, Frick, GP, Bistrian, BR & Smith, RJ (1999) Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo. Endocrinology 140 5505–5515.Google Scholar
Meisenberg, G & Simmons, WH (editors) (1998) Principles of Medical Biochemistry, 1st ed., p. 333. St Louis, MO: Mosby Inc.Google Scholar
Mortlock, RP (1998) Bacterial growth and metabolism. In Microbiology and Microbial Infections, vol. 2, 9th ed., pp. 85–124 [Collier, L, Balows, A and Sussman, M, editors]. London: Arnold.Google Scholar
Muller, S, Martin, S, Koenig, W, Hanifi-Moghaddam, P, Rathmann, W, Haastert, B, Giani, G, Illig, T, Thorand, B & Kolb, H (2002) Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologica 45 805–812.Google Scholar
National Library of Medicine (2005) MeSH database. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=meshGoogle Scholar
Patino, JF, de Pimiento, SE, Vergara, A, Savino, P, Rodriguez, M & Escallon, J (1999) Hypocaloric support in the critically ill. World Journal of Surgery 23 553–559.CrossRefGoogle ScholarPubMed
Pertynska-Marczewska, M, Kiriakidis, S, Wait, R, Beech, J, Feldmann, M & Paleolog, EM (2004) Advanced glycation end products upregulate angiogenic and proinflammatory cytokine production in human monocyte/macrophages. Cytokine 28 35–47.Google Scholar
Philips, BJ, Meguer, J-X, Redman, J & Baker, EH (2003) Factors determining the appearance of glucose in upper and lower respiratory tract secretions. Intensive Care Medicine 29 2204–2210.CrossRefGoogle ScholarPubMed
Philips, BJ, Redman, J, Brennan, AL, Wood, DM, Holliman, R, Baines, DL & Baker, EH (2005) Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients. Thorax 60 761–764.CrossRefGoogle ScholarPubMed
Reading, PC, Allison, J, Crouch, EC & Anders, EM (1998) Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defence of the lung by glucose. Journal of Virology 72 6884–6887.Google Scholar
Reizer, J, Saier, MH Jr, Deutscher, J, Grenier, F, Thompson, J & Hengstenberg, W (1988) The phosphoenolpyruvate: sugar phosphotransferase system in gram-positive bacteria: properties, mechanism, and regulation. Critical Reviews in Microbiology 15 297–338.CrossRefGoogle ScholarPubMed
Rolih, CA & Ober, KP (1995) The endocrine response to critical illness. Medical Clinics of North America 79 211–224.Google Scholar
Ruan, H, Miles, PD, Ladd, CM, Ross, K, Golub, TR, Olefsky, JM & Lodish, HF (2002) Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance. Diabetes 51 3176–3188.Google Scholar
Rui, L, Yuan, M, Frantz, D, Shoelson, S & White, MF (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. Journal of Biological Chemistry 277 42394–42398.Google Scholar
Saumon, G, Martet, G & Loiseau, P (1996) Glucose transport and equilibrium across alveolar-airway barrier of rat. American Journal of Physiology 270 L183–L190.Google ScholarPubMed
Senn, JJ, Klover, PJ, Nowak, IA, Zimmers, TA, Koniaris, LG, Furlanetto, RW & Mooney, RA (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. Journal of Biological Chemistry 278 13740–13746.CrossRefGoogle ScholarPubMed
Sidossis, LS, Mittendorfer, B, Walser, E & Wolfe, RR (1999) Regional disposal of intravenously infused glucose during prolonged hyperglycemia-hyperinsulinemia. Journal of Nutritional Biochemistry 10 547–554.Google Scholar
Straczkowski, M, Kowalska, I, Nikolajuk, A, Dzienis-Straczkowska, S, Szelachowska, M & Kinalska, I (2003) Plasma interleukin 8 concentrations in obese subjects with impaired glucose tolerance. Cardiovascular Diabetology 2 5.CrossRefGoogle ScholarPubMed
Sugahara, K, Freidenberg, GR & Mason, RJ (1984) Insulin binding and effects on glucose and transepithelial transport by alveolar type II cells. American Journal of Physiology 247 C472–C477.Google Scholar
Umpierrez, GE, Isaacs, SD, Bazargan, H, You, X, Thaler, LM & Kitabchi, AE (2002) Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. Journal of Clinical Endocrinology and Metabolism 87 978–982.CrossRefGoogle ScholarPubMed
Van den Berghe, G (2004) How does blood glucose control with insulin save lives in intensive care. Journal of Clinical Investigation 114 1187–1195.CrossRefGoogle ScholarPubMed
Van den Berghe, G, Wouters, PJ, Bouillon, R, Weekers, F, Verwaest, C, Schetz, M, Vlasselaers, D, Ferdinande, P & Lauwers, P (2003) Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control. Critical Care Medicine 31 359–366.CrossRefGoogle ScholarPubMed
Van den Berghe, G, Wouters, P, Weekers, F, Verwaest, C, Bruyninckx, F, Schetz, M, Vlasselaers, D, Ferdinande, P, Lauwers, P & Bouillon, R (2001) Intensive insulin therapy in the critically ill patient. New England Journal of Medicine 345 1359–1367.CrossRefGoogle Scholar
Vanhorebeek, I, De Vos, R, Mesotten, D, Wouters, PJ, De Wolf-Peeters, C & Van den Berghe, G (2005) Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients. Lancet 365 53–59.CrossRefGoogle ScholarPubMed
Vriesendorp, TM, Morelis, QJ, Devries, JH, Legemate, DA & Hoekstra, JB (2004) Early post-operative glucose levels are an independent risk factor for infection after peripheral vascular surgery. A retrospective study. European Journal of Vascular and Endovascular Surgery 28 520–525.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 hyperglycemic glucose clamp technique. Journal of Parenteral and Enteral Nutrition 11 345–353.Google Scholar
Wood, DM, Baines, DL, Woollhead, AM, Philips, BJ & Baker, EH (2004a) Functional and molecular evidence for glucose transporters in human airway epithelium. American Journal of Respiratory and Critical Care Medicine 169 A672Google Scholar
Wood, DM, Brennan, AL, Philips, BJ & Baker, EH (2004b) Effect of hyperglycaemia on glucose concentration of airways secretions. Clinical Science 106 527–533.Google Scholar
Yendarumi, S, Fulda, GJ & Tinkoff, GH (2003) Admission hyperglycemia as a prognostic indicator in trauma. Journal of Trauma 55 33–38.Google Scholar
Yu, W-K, Li, W-Q, Li, N & Li, J-S (2003) Influence of acute hyperglycaemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations. World Journal of Gastroenterology 9 1824–1827.CrossRefGoogle ScholarPubMed