The Role of Insulin Therapy in Critically I11 Patients

Protracted critically ill patients have a seriously deranged metabolism, characterized by severe hyperglycemia, a disturbed serum lipid profile, and protein hypercatabolism. The severity of stress-induced hyperglycemia and insulin resistance in critically ill patients reflect the risk of death. A large, prospective, randomized, controlled study showed that maintaining normoglycemia with intensive insulin therapy reduces morbidity and mortality of surgical intensive care patients. These results were recently confirmed by two studies: one randomized controlled study of surgical intensive care patients and a prospective observational study of a heterogeneous patient population admitted to a mixed medical/surgical intensive care unit. The clinical benefits of intensive insulin therapy appear to be related both to prevention of glucose toxicity and to other direct insulin actions that are independent of glycemic control. Prevention of the toxic effects of high circulating glucose levels protected the ultrastructure and function of hepatocyte mitochondria. Benefits of the non-glycemic effects of insulin included partial correction of the deranged serum lipid profile and possibly counteraction of the catabolic state. In addition to its metabolic effects, intensive insulin therapy also prevented excessive inflammation and improved immune function.

[1]  Greet Van den Berghe,et al.  How does blood glucose control with insulin save lives in intensive care , 2004 .

[2]  A. Rovlias,et al.  The influence of hyperglycemia on neurological outcome in patients with severe head injury. , 2000, Neurosurgery.

[3]  Miet Schetz,et al.  Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control* , 2003, Critical care medicine.

[4]  Neil J Grey,et al.  Reduction of nosocomial infections in the surgical intensive-care unit by strict glycemic control. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[5]  W. Fraser,et al.  Neutrophil Bactericidal Function in Diabetes Mellitus: Evidence for Association with Blood Glucose Control , 1995, Diabetic medicine : a journal of the British Diabetic Association.

[6]  Jan O Friedrich,et al.  Validation of an Insulin Infusion Nomogram for Intensive Glucose Control in Critically Ill Patients , 2005, Pharmacotherapy.

[7]  Salmaan Kanji,et al.  Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults , 2004, Intensive Care Medicine.

[8]  James D Dziura,et al.  Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. , 2004, Diabetes care.

[9]  James Stephen Krinsley,et al.  Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. , 2004, Mayo Clinic proceedings.

[10]  H. Gerstein,et al.  Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview , 2000, The Lancet.

[11]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[12]  M. Agus,et al.  Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation. , 2004, Journal of pediatric surgery.

[13]  M. Quon,et al.  Inhibition of Phosphatidylinositol 3-Kinase Enhances Mitogenic Actions of Insulin in Endothelial Cells* , 2002, The Journal of Biological Chemistry.

[14]  R. Wolfe,et al.  Extremity hyperinsulinemia stimulates muscle protein synthesis in severely injured patients. , 2004, American journal of physiology. Endocrinology and metabolism.

[15]  Dieter Mesotten,et al.  Contribution of circulating lipids to the improved outcome of critical illness by glycemic control with intensive insulin therapy. , 2004, The Journal of clinical endocrinology and metabolism.

[16]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[17]  Yingxing Wu,et al.  Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[18]  G. Van den Berghe,et al.  Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels. , 2003, The Journal of clinical endocrinology and metabolism.

[19]  P. Watson,et al.  Hyperinsulinemia enhances transcriptional activity of nuclear factor-kappaB induced by angiotensin II, hyperglycemia, and advanced glycosylation end products in vascular smooth muscle cells. , 2000, Circulation research.

[20]  R. Wolfe,et al.  Effect of severe burn injury on substrate cycling by glucose and fatty acids. , 1987, The New England journal of medicine.

[21]  J. Wilberger,et al.  The impact of hyperglycemia on patients with severe brain injury. , 2005, The Journal of trauma.

[22]  O. Schmitz,et al.  Acute Hyperinsulinemia Restrains Endotoxin-induced Systemic Inflammatory Response: An Experimental Study in a Porcine Model , 2004, Anesthesiology.

[23]  R. Horch,et al.  Insulin Treatment Improves Hepatic Morphology and Function Through Modulation of Hepatic Signals After Severe Trauma , 2004, Annals of surgery.

[24]  G. Paolisso,et al.  Oxidative Stress and Diabetic Vascular Complications , 1996, Diabetes Care.

[25]  A. Malhotra,et al.  Stress-induced hyperglycemia. , 2001, Critical care clinics.

[26]  F Bruyninckx,et al.  Insulin therapy protects the central and peripheral nervous system of intensive care patients , 2005, Neurology.

[27]  M. Mlynarek,et al.  An Insulin Infusion Protocol in Critically Ill Cardiothoracic Surgery Patients , 2004, The Annals of pharmacotherapy.

[28]  R. Einspanier,et al.  Insulin attenuates the systemic inflammatory response in endotoxemic rats. , 2004, Endocrinology.

[29]  H. Kaneshige Nonenzymatic Glycosylation of Serum IgG and Its Effect on Antibody Activity in Patients With Diabetes Mellitus , 1987, Diabetes.

[30]  D. Chinkes,et al.  Anabolic action of insulin on skin wound protein is augmented by exogenous amino acids. , 2002, American journal of physiology. Endocrinology and metabolism.

[31]  M. Apkon,et al.  Persistent hyperglycemia in critically ill children. , 2005, The Journal of pediatrics.

[32]  E. Barrett,et al.  Extreme hyperinsulinemia unmasks insulin's effect to stimulate protein synthesis in the human forearm. , 1998, American journal of physiology. Endocrinology and metabolism.

[33]  O. Ljungqvist,et al.  Insulin resistance: a marker of surgical stress. , 1999, Current opinion in clinical nutrition and metabolic care.

[34]  H. Gerstein,et al.  Stress Hyperglycemia and Prognosis of Stroke in Nondiabetic and Diabetic Patients: A Systematic Overview , 2001, Stroke.

[35]  A. Marette,et al.  Regulation of expression of glucose transporters by glucose: a review of studies in vivo and in cell cultures , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  G. Van den Berghe,et al.  Metabolic, endocrine, and immune effects of stress hyperglycemia in a rabbit model of prolonged critical illness. , 2003, Endocrinology.

[37]  J Wayne Meredith,et al.  Relationship of early hyperglycemia to mortality in trauma patients. , 2004, The Journal of trauma.

[38]  Timothy W. Evans,et al.  Glucose Control and Mortality in Critically Ill Patients , 2003 .

[39]  A. Hays,et al.  Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes. , 2004, Diabetes.

[40]  G. Van den Berghe,et al.  Regulation of insulin-like growth factor binding protein-1 during protracted critical illness. , 2002, The Journal of clinical endocrinology and metabolism.

[41]  R. Wolfe,et al.  Glucose metabolism in severely burned patients. , 1979, Metabolism: clinical and experimental.

[42]  D. Chinkes,et al.  Association of hyperglycemia with increased mortality after severe burn injury. , 2001, The Journal of trauma.

[43]  I. West Radicals and oxidative stress in diabetes , 2000, Diabetic medicine : a journal of the British Diabetic Association.

[44]  C. Wolf‐peeters,et al.  Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients , 2005, The Lancet.

[45]  Nielson Cp,et al.  Inhibition of Polymorphonuclear Leukocyte Respiratory Burst by Elevated Glucose Concentrations in Vitro , 1989 .

[46]  H. Harris,et al.  Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. , 1993, The Journal of clinical investigation.

[47]  L. McManus,et al.  Agonist‐dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia , 2001, Journal of leukocyte biology.

[48]  Seema Sharma,et al.  Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[49]  U. Das Is insulin an antiinflammatory molecule? , 2001, Nutrition.

[50]  H. Harris,et al.  Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. , 1990, The Journal of clinical investigation.

[51]  G. Tinkoff,et al.  Admission hyperglycemia as a prognostic indicator in trauma. , 2003, The Journal of trauma.

[52]  R. Holman,et al.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. , 1998 .

[53]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[54]  B. Genetet,et al.  Impaired Leucocyte Functions in Diabetic Patients , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[55]  Paul Taylor,et al.  Research Paper: Use of a Computerized Guideline for Glucose Regulation in the Intensive Care Unit Improved Both Guideline Adherence and Glucose Regulation , 2004, J. Am. Medical Informatics Assoc..

[56]  G. Caimi,et al.  Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells , 2000, Diabetologia.

[57]  Dagmar Klein,et al.  Insulin Treatment Improves the Systemic Inflammatory Reaction to Severe Trauma , 2004, Annals of surgery.

[58]  A. Aljada,et al.  Insulin as an anti-inflammatory and antiatherosclerotic hormone. , 2003, Clinical cornerstone.

[59]  O. Wieland,et al.  Nonenzymatic glycation of immunoglobulins leads to an impairment of immunoreactivity. , 1985, Biological chemistry Hoppe-Seyler.