Aktuelle Ernährungsmedizin 2006; 31: 81-88
DOI: 10.1055/s-2005-915362
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Blutzucker in der Intensivmedizin

Blood Glucose Concentration and Critical CareW.  H.  Hartl1 , K.-W.  Jauch1
  • 1Chirurgische Klinik und Poliklinik, Klinikum Großhadern, LMU München
Further Information

Publication History

Publication Date:
14 February 2006 (online)

Zusammenfassung

Eine stressbedingte Hyperglykämie und eine Insulinresistenz sind bei kritisch kranken Patienten überaus häufig anzutreffen, insbesondere in Verbindung mit septischen Zustandsbildern. Verschiedene pathogenetische Mechanismen sind dabei für dieses spezielle Phänomen des Postaggressionsstoffwechsels verantwortlich. Eine zentrale Bedeutung spielt dabei die vermehrte Freisetzung von proinflammatorischen Mediatoren (Zytokinen) und antiinsulinären Hormonen (Glukagon, Katecholamine, Kortisol). In jüngster Zeit verdichten sich die Informationen, dass eine lang anhaltende ausgeprägte Hyperglykämie die proinflammatorischen, autoaggressiven Mechanismen des Intensivpatienten verstärken kann, während eine gleichzeitige Insulintherapie hier antagonistisch wirkt. Es gibt zusätzlich überzeugende Hinweise dafür, dass eine engmaschige Blutzuckerkontrolle und scharfe Blutzuckereinstellung die Prognose des kritisch kranken Patienten verbessern kann. Inwieweit tatsächlich eine Absenkung des Blutzuckerspiegels oder die zusätzliche Verabreichung von mehr Insulin hier ursächlich sind, kann zum gegenwärtigen Zeitpunkt noch nicht eindeutig entschieden werden.

Abstract

Stress-induced hyperglycemia and insulin resistance are common phenomena in critically ill patients, particularly in those suffering from severe sepsis. Several mechanisms may explain this characteristic change of substrate metabolism during the post-injury catabolic response (flow phase). A crucial role can be attributed to the enhanced release of pro-inflammatory mediators (cytokines) and catabolic hormones (glucagon, catecholamines, cortisol). Recently, there is growing evidence that prolonged and profound hyperglycemia may potentiate pro-inflammatory, potentially harmful reactions in critically ill patients, whereas a simultaneous insulin therapy may antagonize these alterations. Furthermore, several clinical studies suggest that tight control of blood glucose concentration may significantly improve morbidity and mortality of critically ill patients. Thus far, it is still unclear which of the two therapeutic interventions (lowering of blood glucose concentration or insulin administration) is responsible for the observed beneficial effects.

Literatur

  • 1 Hartl W H, Jauch K W. Postaggressionsstoffwechsel: Versuch einer Standortbestimmung.  Infusionstherapie. 1994;  21 30-40
  • 2 Bernard C. Leçons sur le diabète et la glycogenèse animale. Paris; Baillière 1877: p210
  • 3 Howard J M. Studies of the absorption and metabolism of glucose following injury.  Ann Surg. 1955;  141 321-325
  • 4 Long C L, Spencer J L, Kinney J M, Geiger J W. Carbohydrate metabolism in man: effect of elective operations and major injury.  J Appl Physiol. 1971;  31 110-116
  • 5 McCowen K C, Malhotra A, Bistrian B R. Stress-induced hyperglycemia.  Crit Care Clin. 2001;  17 107-124
  • 6 Berghe G Van den, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients.  N Engl J Med. 2001;  345 1359-1367
  • 7 Frankenfield D C, Omert L A, Badellino M M, Wiles III C E, Bagley S M, Goodarzi S, Siegel J H. Correlation between measured energy expenditure and clinically obtained variables in trauma and sepsis patients.  J Parenter Enteral Nutr. 1994;  18 398-403
  • 8 Marik P E, Zaloga G P. Adrenal insufficiency in the critically ill: a new look at an old problem.  Chest. 2002;  122 1784-1796
  • 9 Hart B B, Stanford G G, Ziegler M G, Lake C R, Chernow B. Catecholamines: study of interspecies variation.  Crit Care Med. 1989;  17 1203-1218
  • 10 Berghe G Van den. Neuroendocrine pathobiology of chronic illness.  Crit Care Clin. 2002;  18 509-528
  • 11 Siegel J H, Cerra F B, Coleman B, Giovannini I, Shetye M, Border J R, McMenamy R H. Physiological and metabolic correlations in human sepsis. Invited commentary.  Surgery. 1979;  86 163-193
  • 12 Clowes G H, Martin H, Walji S, Hirsch E, Gazitua R, Goodfellow R. Blood insulin responses to blood glucose levels in high output sepsis and septic shock.  Am J Surg. 1978;  135 577-583
  • 13 Dahn M S, Jacobs L A, Smith S, Hans B, Lange M P, Mitchell R A, Kirkpatrick J R. The relationship of insulin production to glucose metabolism in severe sepsis.  Arch Surg. 1985;  120 166-172
  • 14 Mizock B A. Alterations in fuel metabolism in critical illness hyperglycemia.  Best Pract Res Clin Endocrinol Metab. 2001;  15 533-551
  • 15 Mehta V K, Hao W, Brooks-Worrell B M, Palmer J P. Low-dose interleukin 1 and tumor necrosis factor individually stimulate insulin release but in combination cause suppression.  Eur J Endocrinol. 1994;  130 208-214
  • 16 Agwunobi A O, Reid C, Maycock P, Little R A, Carlson G L. Insulin resistance and substrate utilization in human endotoxemia.  J Clin Endocrinol Metab. 2000;  85 3770-3778
  • 17 Sakurai Y, Zhang X J, Wolfe R R. TNF directly stimulates glucose uptake and leucine oxidation and inhibits FFA flux in conscious dogs.  Am J Physiol. 1996;  270 E864-E872
  • 18 Lang C H, Dobrescu C. Gramnegative infection increases noninsulin-mediated glucose disposal.  Endocrinology. 1991;  128 645-653
  • 19 Meszaros K, Lang C H, Bagby G J, Spitzer J J. Tumor necrosis factor increases in vivo glucose utilization of macrophage-rich tissues.  Biochem Biophys Res Commun. 1987;  149 1-6
  • 20 Bird T A, Davies A, Baldwin S A, Saklatvala J. Interleukin 1 stimulates hexose transport in fibroblasts by increasing the expression of glucose transporters.  J Biol Chem. 1990;  265 13578-13583
  • 21 Saeed M, Carlson G L, Little R A, Irving M H. Selective impairment of glucose storage in human sepsis.  Br J Surg. 1999;  86 813-821
  • 22 Green C J, Campbell I T, O'Sullivan E, Underhill S, McLaren D P, Hipkin L J, MacDonald I A, Russell J. Septic patients in multiple organ failure can oxidize infused glucose, but nonoxidative disposal (storage) is impaired.  Clin Sci. 1995;  89 601-609
  • 23 Mizock B A. Alterations in fuel metabolism in critical illness. Hyperglycemia. In: Ober KP (ed) Endocrinology of critical disease. Totawa, New Jersey; Humana Press 1997: 197-297
  • 24 Jeevanandam M, Young D H, Schiller W R. Glucose turnover, oxidation, and indices of recycling in severely traumatized patients.  J Trauma. 1990;  30 582-589
  • 25 Mesotten D, Delhanty P J, Vanderhoydonc F, Hardman K V, Weekers F, Baxter R C, Berghe G Van den. Regulation of insulin-like growth factor binding protein-1 during protracted critical illness.  J Clin Endocrinol Metab. 2002;  87 5516-5523
  • 26 Cerra F B. Hypermetabolism, organ failure, and metabolic support.  Surgery. 1987;  101 1-14
  • 27 Wolfe R R. Substrate utilization/insulin resistance in sepsis/trauma.  Baillieres Clin Endocrinol Metab. 1997;  11 645-657
  • 28 Petit F, Bagby G J, Lang C H. Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance.  Am J Physiol. 1995;  268 E219-E228
  • 29 Roh M S, Moldawer L L, Ekman L G, Dinarello C A, Bistrian B R, Jeevanandam M, Brennan M F. Stimulatory effect of interleukin-1 upon hepatic metabolism.  Metabolism. 1986;  35 419-424
  • 30 Lang C H. Sepsis-induced insulin resistance in rats is mediated by a beta-adrenergic mechanism.  Am J Physiol. 1992;  263 E703-E711
  • 31 Chambrier C, Laville M, Rhzioual B K, Odeon M, Bouletreau P, Beylot M. Insulin sensitivity of glucose and fat metabolism in severe sepsis.  Clin Sci. 2000;  99 321-328
  • 32 Pessin J E, Saltiel A R. Signaling pathways in insulin action: molecular targets of insulin resistance.  J Clin Invest. 2000;  106 165-169
  • 33 Aljada A, Ghanim H, Assian E, Dandona P. Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells.  Metabolism. 2002;  51 487-491
  • 34 Hotamisligil G S, Peraldi P, Budavari A, Ellis R, White M F, Spiegelman B M. IRS-1 mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity induced insulin resistance.  Science. 1996;  271 665-668
  • 35 Kanety H, Feinstein R, Papa M Z, Hemi R, Karasik A. Tumor necrosis factor alpha induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1.  J Biol Chem. 1995;  270 23780-23784
  • 36 Paz K, Hemi R, LeRoith D, Karasik A, Elhanany E, Kanety H, Zick Y. A molecular basis for insulin resistance. Elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation.  J Biol Chem. 1997;  272 29911-29918
  • 37 Nunes A L, Carvalheira J B, Carvalho C R, Brenelli S L, Saad M J. Tissue-specific regulation of early steps in insulin action in septic rats.  Life Sci. 2001;  69 2103-2112
  • 38 Chiasson J L, Shikama H, Chu D T, Exton J H. Inhibitory effect of epinephrine on insulin-stimulated glucose uptake by rat skeletal muscle.  J Clin Invest. 1981;  68 706-713
  • 39 Haring H, Kirsch D, Obermaier B, Ermel B, Machicao F. Decreased tyrosine kinase activity of insulin receptor isolated from rat adipocytes rendered insulin-resistant by catecholamine treatment in vitro.  Biochem J. 1986;  234 59-66
  • 40 Dimitriadis G, Leighton B, Parry-Billings M, Sasson S, Young M, Krause U, Bevan S, Piva T, Wegener G, Newsholme E A. Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle.  Biochem J. 1997;  321 707-712
  • 41 Smith T R, Elmendorf J S, David T S, Turinsky J. Growth hormoneinduced insulin resistance: role of the insulin receptor, IRS-1, GLUT-1, and GLUT-4.  Am J Physiol. 1997;  272 E1071-E1079
  • 42 Dominici F P, Cifone D, Bartke A, Turyn D. Alterations in the early steps of the insulin-signaling system in skeletal muscle of GHtransgenic mice.  Am J Physiol. 1999;  277 E447-E454
  • 43 Stuart C A, Shangraw R E, Prince M J. et al . Bed-rest-induced insulin resistance occurs primarily in muscle.  Metabolism. 1988;  37 802-806
  • 44 Shangraw R E, Jahoor F, Miyoshi H. et al . Differentiation between septic and postburn insulin resistance.  Metabolism. 1989;  38 983-989
  • 45 Pomerantz W J, Hashkes P J, Succop P A, Dowd M D. Relationship between serum glucose and injury severity score in childhood trauma.  J Pediatr Surg. 1999;  34 1494-1498
  • 46 Norhammar A M, Ryden L, Malmberg K. Admission plasma glucose. Independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients.  Diabetes Care. 1999;  22 1827-1831
  • 47 Zindrou D, Taylor K M, Bagger J P. Admission plasma glucose: an independent risk factor in nondiabetic women after coronary artery bypass grafting.  Diabetes Care. 2001;  24 1634-1639
  • 48 Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: longterm results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study.  Circulation. 1999;  99 2626-2632
  • 49 Malmberg K. Prospective randomised study of intensive insulin treatment on long-term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.  Br Med J. 1997;  314 1512-1515
  • 50 Malmberg K, Ryden L, Efendic S, Herlitz J, Nicol P, Waldenstrom A, Wedel H, Welin L. 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.  J Am Coll Cardiol. 1995;  26 57-65
  • 51 Capes S E, Hunt D, Malmberg K, Pathak P, Gerstein H C. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.  Stroke. 2001;  32 2426-2432
  • 52 Woo J, Lam C W, Kay R, Wong A H, Teoh R, Nicholls M G. The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke.  Arch Neurol. 1990;  47 1174-1177
  • 53 Laird A M, Miller P R, Kilgo P D, Meredith J W, Chang M C. Relationship of early hyperglycemia to mortality in trauma patients.  J Trauma. 2004;  56 1058-1062
  • 54 Gore D C, Chinkes D, Heggers J, Herndon D N, Wolf S E, Desai M. Association of hyperglycemia with increased mortality after severe burn injury.  J Trauma. 2001;  51 540-544
  • 55 Dandona P, Aljada A, Bandyopadhyay A. The potential therapeutic role of insulin in acute myocardial infarction in patients admitted to intensive care and in those with unspecified hyperglycemia.  Diabetes Care. 2003;  26 516-519
  • 56 Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes.  J Clin Endocrinol Metab. 2000;  85 2970-2973
  • 57 Straczkowski M, Dzienis-Straczkowska S, Stepien A, Kowalska I, Szelachowska M, Kinalska I. Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system.  J Clin Endocrinol Metab. 2002;  87 4602-4606
  • 58 Chettab K, Zibara K, Belaiba S R, McGregor J L. Acute hyperglycaemia induces changes in the transcription levels of 4 major genes in human endothelial cells: macroarraysbased expression analysis.  Thromb Haemost. 2002;  87 141-148
  • 59 Standiford T J, Kunkel S L, Greenberger M J, Laichalk L L, Strieter R M. Expression and regulation of chemokines in bacterial pneumonia.  J Leukoc Biol. 1996;  59 24-28
  • 60 Hack C E, Aarden L A, Thijs L G. Role of cytokines in sepsis.  Adv Immunol. 1997;  66 101-195
  • 61 Multz A S, Cohen R. Systemic response to pneumonia in the critically ill patient.  Semin Resp Infect. 2003;  18 68-71
  • 62 Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P. Glucose activates nuclear factor kappa B pathway in mononuclear cells (MNC) and induces an increase in p47phox. subunit in MNC membranes [Abstract].  Diabetes. 2002;  51 (Suppl 2) A537
  • 63 Yorek M A, Dunlap J A. Effect of increased concentration of D-glucose or L-fucose on monocyte adhesion to endothelial cell monolayers and activation of nuclear factor-kappaB.  Metabolism. 2002;  51 225-234
  • 64 Guha M, Bai W, Nadler J L, Natarajan R. Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stressdependent and -independent pathways.  J Biol Chem. 2000;  275 17728-17739
  • 65 Ceriello A, Bortolotti N, Motz E, Pieri C, Marra M, Tonutti L, Lizzio S, Feletto F, Catone B, Taboga C. Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia.  Metabolism. 1999;  48 1503-1508
  • 66 Ceriello A. Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects.  Diabetologia. 1993;  36 1119-1125
  • 67 Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C, D'Onofrio F. Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia.  Circulation. 1997;  95 1783-1790
  • 68 Nielson C P, Hindson D A. Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose concentrations in vitro.  Diabetes. 1989;  38 1031-1035
  • 69 Kwoun M O, Ling P R, Lydon E, Imrich A, Qu Z, Palombo J, Bistrian B R. Immunologic effects of acute hyperglycemia in nondiabetic rats.  J Parenter Enteral Nutr. 1997;  21 91-95
  • 70 Pittas A G, Siegel R D, Lau J. Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials.  Arch Intern Med. 2004;  164 2005-2011
  • 71 Krinsley J S. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.  Mayo Clin Proc. 2004;  79 992-1000
  • 72 Finney S J, Zekveld C, Elia A, Evans T W. Glucose control and mortality in critically ill patients.  JAMA. 2003;  290 2041-2047
  • 73 Berghe G Van den, Wouters P J, Bouillon R, Weekers F, Verwaest C, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P. Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control.  Crit Care Med. 2003;  31 359-366
  • 74 Dandona P, Aljada A, Mohanty P, Ghanim H, Hamouda W, Assian E, Ahmad S. Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?.  J Clin Endocrinol Metab. 2001;  86 3257-3265
  • 75 Aljada A, Dandona P. Effect of insulin on human aortic endothelial nitric oxide synthase.  Metabolism. 2000;  49 147-150
  • 76 Peng H B, Spiecker M, Liao J K. Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation.  J Immunol. 1998;  161 1970-1976
  • 77 Spiecker M, Darius H, Kaboth K, Hubner F, Liao J K. Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants.  J Leukoc Biol. 1998;  63 732-739
  • 78 Spiecker M, Peng H B, Liao J K. Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha.  J Biol Chem. 1997;  272 30969-30974
  • 79 Meldrum D R, McIntyre R C, Sheridan B C, Cleveland Jr J C, Fullerton D A, Harken A H. L-arginine decreases alveolar macrophage proinflammatory monokine production during acute lung injury by a nitric oxide synthase-dependent mechanism.  J Trauma. 1997;  43 888-893
  • 80 Laroux F S, Lefer D J, Kawachi S, Scalia R, Cockrell A S, Gray L, Heyde H van der, Hoffman J M, Grisham M B. Role of nitric oxide in the regulation of acute and chronic inflammation.  Antioxidants Redox Signaling. 2000;  2 391-396
  • 81 Berghe G Van den. How does blood glucose control with insulin save lives in intensive care?.  J Clin Invest. 2004;  114 1187-1195
  • 82 Tarnow-Mordi W O, Hau C, Warden A, Shearer A J. Hospital mortality in relation to staff workload: a 4-year study in an adult intensive-care unit.  Lancet. 2000;  356 185-189
  • 83 Aiken L H, Clarke S P, Sloane D M, Sochalski J, Silber J H. Hospital nurse staffing and patient mortality, nurse burnout, and job dissatisfaction.  JAMA. 2002;  288 1987-1993

PD Dr. med. W. H. Hartl

Chirurgische Klinik · Klinikum Großhadern

Marchioninistraße 15

81377 München

Email: whartl@med.uni-muenchen.de

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