Reference Type: Electronic Source
Record Number: 49
Year: 2004
Title: Insulin synthesis and secretion
Access Year: 2004
Access Date: 07.08.
URL: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin.html

Reference Type: Electronic Source
Record Number: 50
Year: 2004
Title: Physiologic effects of insulin
Access Year: 2004
Access Date: 08.07.
URL: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html

Reference Type: Book
Record Number: 70
Year: 2003
Title: Definition nosokomialer Infektionen (CDC-Definitionen)
Series Editor: Infektionen, Nationales Referenzzentrum (NRZ) für Surveillance von nosokomialen
City: Berlin
Publisher: Robert-Koch-Institut
Edition: 4
URL: http://www.rki.de/GESUND/HYGIENE/DNI/NOSO-INF.PDF

Reference Type: Journal Article
Record Number: 15
Author: Szabo, Z.; Hakanson, E.; Maros, T.; Svedjeholm, R.
Year: 2003
Title: High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues
Journal: Acta Anaesthesiol Scand
Volume: 47
Issue: 4
Pages: 383-90
Date: Apr
Accession Number: 12694134
Keywords: Aged
Blood Glucose/analysis
Cardiac Output, Low/etiology/*therapy
Cardiac Surgical Procedures/*adverse effects
Critical Illness
Diabetes Mellitus, Type II/blood
Female
Glucose/*administration & dosage/adverse effects
Hemodynamic Processes
Human
Insulin/*administration & dosage/adverse effects
Male
Myocardial Ischemia/etiology/*therapy
Postoperative Complications/*therapy
Potassium/*administration & dosage/adverse effects/blood
Retrospective Studies
Vascular Resistance/drug effects
Abstract: BACKGROUND: Metabolic treatment with insulin or glucose-insulin-potassium (GIK) has received attention in association with myocardial infarction, cardiac surgery and critical care. As a result of insulin resistance during neuroendocrine stress, doses of insulin up to 1 IU kg-1 b.w.*h are required to achieve maximal metabolic effects after cardiac surgery. The clinical experience with regard to safety issues of such a high-dose GIK regime in critically ill patients after cardiac surgery is reported. METHODS: Retrospective, observational study involving all patients treated with high-dose GIK after cardiac surgery during one year in a cardiovascular center at a University Hospital. RESULTS: Eighty-nine patients out of 854 adult patients undergoing cardiac surgery were treated with high-dose GIK. Mean age was 69 +/- 1 years, Higgins score 5.3 +/- 0.3. Preoperatively 31.4% had left ventricular function EF< or =0.35 and 32.5% had sustained a myocardial infarct during surgery. Mortality was 5.6% and the average ICU stay was 3.7 +/- 0.5 days. The main indication for GIK was intraoperative heart failure (69.7%). The average glucose infusion rate during the first 6 h was 4.22 +/- 0.15 and 4.91 +/- 0.14 mg kg-1 b.w.*min, respectively, in diabetic and non-diabetic patients (P = 0.023). Blood glucose and s-potassium control was acceptable. CONCLUSIONS: The high-dose GIK regime allowed substantial amounts of glucose to be infused both in diabetic and critically ill patients with maintenance of acceptable blood glucose control. Provided careful monitoring, this regime can be safely used in clinical practice and deserves further evaluation for treatment of critically ill patients following cardiac surgery.
Notes: 0001-5172
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12694134
Author Address: Departments of Cardiothoracic Anesthesia and Intensive Care and Cardiothoracic Surgery, Linkoping Heart Center, University Hospital, Linkoping, Sweden. Zoltan.Szabo@lio.se

Reference Type: Book Section
Record Number: 75
Author: Karow, T.; Lang-Roth, R.
Year: 2004
Title: Orale Antidiabetika
Book Title: Allgemeine und spezielle Pharmakologie und Toxikologie
Pages: 642-645

Reference Type: Journal Article
Record Number: 73
Author: Shulman, G. I.
Year: 1999
Title: Cellular mechanisms of insulin resistance in humans
Journal: Am J Cardiol
Volume: 84
Issue: 1A
Pages: 3J-10J
Date: Jul 8
Accession Number: 10418851
Keywords: Diabetes Mellitus, Type II/drug therapy/*metabolism/*physiopathology
Glucose/*metabolism
Glycogen/biosynthesis
Human
Hypoglycemic Agents/metabolism/therapeutic use
Insulin/metabolism
Insulin Resistance/*physiology
Liver/*metabolism
Magnetic Resonance Spectroscopy
Muscles/*metabolism
Abstract: Carbon nuclear magnetic resonance (13C NMR) spectroscopy and phosphorus (31p) NMR spectroscopy have been used to help define the contribution of insulin-stimulated muscle glycogen synthesis to whole-body insulin-stimulated glucose metabolism in normal individuals and the extent to which this process is defective in patients with type 2 (non-insulin-dependent) diabetes. Assessments of the response to hyperglycemic-hyperinsulinemic clamping have shown that abnormalities of muscle glycogen synthesis, apparently mediated by a defect in GLUT-4 transport and/or hexokinase activity, play a major role in causing insulin resistance in type 2 diabetes. Studies of the mechanisms by which free fatty acids (FFA) cause insulin resistance in humans indicate that increased FFA levels inhibit glucose transport, which may be a consequence of decreased insulin receptor substrate (IRS-1)-associated phosphatidylinositol 3-kinase activity. 13C NMR spectroscopy studies have documented that liver glycogen concentrations are reduced and the rate of hepatic gluconeogenesis is increased in subjects with type 2 diabetes; thus, the higher rate of glucose production in type 2 diabetes can be attributed entirely to increased rates of hepatic gluconeogenesis. These cellular mechanisms of insulin resistance can be addressed through combination therapy with agents that reverse the principal pathophysiologic defects of type 2 diabetes. The biguanide metformin appears to lower glucose by suppressing hepatic glucose production, whereas the thiazolidinedione troglitazone appears to increase glucose clearance by peripheral tissues. The two agents together have been shown to provide better glucose control than either drug alone, without stimulating insulin secretion.
Notes: 0002-9149
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10418851
Author Address: Howard Hughes Medical Institute and Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA.

Reference Type: Journal Article
Record Number: 65
Author: Gore, D. C.; Wolf, S. E.; Sanford, A. P.; Herndon, D. N.; Wolfe, R. R.
Year: 2004
Title: Extremity hyperinsulinemia stimulates muscle protein synthesis in severely injured patients
Journal: Am J Physiol Endocrinol Metab
Volume: 286
Issue: 4
Pages: E529-34
Date: Apr
Accession Number: 14665444
Keywords: Adult
Algorithms
Amino Acids/metabolism
Blood Glucose/metabolism
Burns/metabolism
Cell Membrane/metabolism
Critical Illness
Female
Human
Hyperinsulinism/*metabolism
Insulin/blood/*pharmacology
Insulin Resistance/physiology
Kinetics
Male
Mass Fragmentography
Middle Aged
Models, Biological
Muscle Proteins/*biosynthesis
Muscle, Skeletal/metabolism
Phenylalanine/blood
Support, Non-U.S. Gov't
Wounds and Injuries/*metabolism
Abstract: Insulin has a well-recognized anabolic effect on muscle protein, yet critically ill, severely injured patients are often considered "resistant" to the action of insulin. The purpose of this study was to assess the in vivo effects of hyperinsulinemia on human skeletal muscle in severely injured patients. To accomplish this goal, 14 patients with burns encompassing >40% of their body surface area underwent metabolic evaluation utilizing isotopic dilution of phenylalanine, femoral artery and vein blood sampling, and sequential muscle biopsies of the leg. After baseline metabolic measurements were taken, insulin was infused into the femoral artery at 0.45 mIU.min(-1).100 ml leg volume(-1) to create a local hyperinsulinemia but with minimal systemic perturbations. Insulin administration increased femoral venous concentration of insulin (P < 0.01) but with only a 4% (insignificant) decrease in the arterial glucose concentration and a 7% (insignificant) decrease in the arterial concentration of phenylalanine. Extremity hyperinsulinemia significantly increased leg blood flow (P < 0.05) and the rate of muscle protein synthesis (P < 0.05). Neither the rate of muscle protein breakdown nor the rate of transmembrane transport of phenylalanine was significantly altered with extremity hyperinsulinemia. In conclusion, this study demonstrates that insulin directly stimulates muscle protein synthesis in severely injured patients.
Notes: 0193-1849
Clinical Trial
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14665444
Author Address: The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1172, USA. dcgore@utmb.edu

Reference Type: Journal Article
Record Number: 24
Author: Jeschke, M. G.
Year: 2003
Title: Intensivierte Insulintherapie bei Sepsis
Journal: Anaesthesist
Volume: 52 Suppl 1
Pages: S20-3
Date: Dec
Accession Number: 14727047
Keywords: Critical Illness
Cytokines/physiology
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Intensive Care
Liver/physiopathology
Sepsis/*drug therapy/*metabolism
Notes: 0003-2417
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14727047
Author Address: Abteilung fur Plastische und Handchirurgie, Friedrich-Alexander-Universitat Erlangen, Erlangen. Mcjeschke@hotmail.com

Reference Type: Journal Article
Record Number: 23
Author: Weigand, M. A.; Bardenheuer, H. J.; Bottiger, B. W.
Year: 2003
Title: Klinisches Management bei Patienten mit Sepsis
Journal: Anaesthesist
Volume: 52
Issue: 1
Pages: 3-22
Date: Jan
Accession Number: 12577161
Keywords: Anti-Infective Agents/therapeutic use
English Abstract
Human
Life Support Systems
Sepsis/diagnosis/epidemiology/physiopathology/*therapy
Terminology
Abstract: Sepsis and septic shock are the leading causes of death in non-cardiological intensive care units in developed countries despite recent advances in critical care medicine.Sepsis is the systemic inflammatory response to infection, often associated with hypoperfusion followed by tissue injury and organ failure.Activation of monocytes/macrophages and neutrophils with consecutive release of proinflammatory mediators and activation of the coagulation cascade, seem to play a key role in the pathogenesis of sepsis.Elimination of the septic focus,antimicrobial therapy and supportive treatment are the cornerstones of sepsis therapy.Adequate and rapid volume replacement and if necessary application of catecholamines are of highest priority to optimize tissue perfusion.Norepinephrine is the vasopressor of choice and dobutamine the preferred inotropic agent. Most experts recommend hemoglobin levels of 8-10 g/dl in severe sepsis.In addition,lung protective ventilatory strategies as well as enteral and parenteral nutrition are part of the clinical management of septic patients.In mechanically ventilated patients intensive insulin therapy to maintain blood glucose at a level between 80 and 110 mg/dl has significantly reduced mortality.Furthermore,prophylaxis of deep vein thrombosis and of stress ulcer bleeding are individually applied to septic patients.Treatment of septic patients with anti-mediator strategies or high dose AT III were not successful so far.In contrast,now two new promising treatment options may be emerging: application of small doses hydrocortisone and activated protein C [drotrecogin alfa (activated)]. Large and in part multicentric studies especially in the last 2 years now allow the practicing clinician to perform a partially evidence-based management of patients with sepsis.In addition, for the first time two options for specific therapy of sepsis,application of small doses hydrocortisone and activated protein C [drotrecogin alfa (activated)],are available which may further improve prognosis for septic patients.
Notes: 0003-2417
Journal Article
Review
Review, Academic
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12577161
Author Address: Klinik fur Anaesthesiologie, Universitatsklinikum Heidelberg. Markus_Weigand@med.uni-heidelberg.de

Reference Type: Journal Article
Record Number: 19
Author: Bates, D. W.
Year: 2002
Title: Unexpected hypoglycemia in a critically ill patient
Journal: Ann Intern Med
Volume: 137
Issue: 2
Pages: 110-6
Date: Jul 16
Accession Number: 12118966
Keywords: Aged
Coronary Artery Bypass
Critical Care/*standards
Female
Human
Hypoglycemia/*chemically induced/prevention & control
Hypoglycemic Agents/administration & dosage
Iatrogenic Disease/epidemiology/*prevention & control
Insulin/administration & dosage
Intensive Care Units/*standards
Medication Errors/*prevention & control
Outcome and Process Assessment (Health Care)
Support, Non-U.S. Gov't
Abstract: Administration of the wrong medication is a serious and understudied problem. Because physicians are not directly involved in the drug administration process, they tend to overlook the possibility of adverse drug events and medication errors in their differential diagnoses of patient illnesses or acute deterioration. This article analyzes the case of a patient with iatrogenic hypoglycemia due to administration of the wrong medication: Insulin instead of heparin was used to flush the patient's arterial line. In addition to assessing the results of the institution's "root-cause analysis" of the factors contributing to this particular adverse event and the institution's response, this article reviews the literature on preventing medication errors. Key strategies that might have been helpful in this case include using checklists for common emergency conditions (such as altered level of consciousness) and automated paging for "panic laboratory values," as well as instituting protocols for medication administration. Changing the system of administering medications by bar coding drugs, with checks of the medication, patient, and provider, could have prevented this accident. Finally, organizations need to strive for a "culture of safety" by providing opportunities to discuss errors and adverse events in constructive, supportive environments and by resisting pressure to find a scapegoat.
Notes: 1539-3704
Case Reports
Clinical Conference
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12118966
Author Address: Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. dbates@partners.org

Reference Type: Journal Article
Record Number: 79
Author: Lewis, K. S.; Kane-Gill, S. L.; Bobek, M. B.; Dasta, J. F.
Year: 2004
Title: Intensive insulin therapy for critically ill patients
Journal: Ann Pharmacother
Volume: 38
Issue: 7-8
Pages: 1243-51
Date: Jul-Aug
Accession Number: 15187219
Abstract: OBJECTIVE: To evaluate the clinical outcomes of glycemic control of intensive insulin therapy and recommend its place in the management of critically ill patients. DATA SOURCES: Searches of MEDLINE (1966-March 2004) and Cochrane Library, as well as an extensive manual review of abstracts were performed using the key search terms hyperglycemia, insulin, intensive care unit, critically ill, outcomes, and guidelines and algorithms. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS: Mortality among patients with prolonged critical illness exceeds 20%, and most deaths are attributable to sepsis and multisystem organ failure. Hyperglycemia is common in critically ill patients, even in those with no history of diabetes mellitus. Maintaining normoglycemia with insulin in critically ill patients has been shown to improve neurologic, cardiovascular, and infectious outcomes. Most importantly, morbidity and mortality are reduced with aggressive insulin therapy. This information can be implemented into protocols to maintain strict control of glucose. CONCLUSIONS: Use of insulin protocols in critically ill patients improves blood glucose control and reduces morbidity and mortality in critically ill populations. Glucose levels in critically ill patients should be controlled through implementation of insulin protocols with the goal to achieve normoglycemia, regardless of a history of diabetes. Frequent monitoring is imperative to avoid hypoglycemia.
Notes: 1060-0280
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15187219
Author Address: Associate Professor of Anesthesiology, Division of Critical Care, Rush Presbyterian St Luke's Medical Center, Chicago, IL, USA.

Reference Type: Journal Article
Record Number: 9
Author: Carlson, G. L.
Year: 2004
Title: Hunterian Lecture: Insulin resistance in human sepsis: implications for the nutritional and metabolic care of the critically ill surgical patient
Journal: Ann R Coll Surg Engl
Volume: 86
Issue: 2
Pages: 75-81
Date: Mar
Accession Number: 15005922
Keywords: Critical Care
Critical Illness/*therapy
Human
Insulin Resistance/*physiology
Parenteral Nutrition, Total/methods
Postoperative Care/methods
Sepsis/*complications
Support, Non-U.S. Gov't
Abstract: Loss of the anabolic effect of insulin (insulin resistance) is a key component of the adverse metabolic consequences of sepsis and may contribute to the apparent lack of efficacy of feeding regimens in critically ill patients. The mechanisms which underlie the development of insulin resistance in stress remain unclear. In this series of studies, the locus of insulin resistance in the septic patient was shown to lie within the metabolic pathways of glucose storage (glycogen synthesis) within skeletal muscle, was noted to be unrelated to the actions of hormone mediators such as leptin and was shown not to be associated with altered nutrient-induced thermogenesis during total parenteral nutrition (TPN). Clinically applicable maximal rates of glucose-based TPN for septic patients were calculated. A technique was also developed in which insulin resistance could be induced and studied in healthy volunteers. These studies demonstrated that insulin resistance develops within 7 h of an inflammatory stimulus and, as in clinical sepsis, is characterised by selective impairment of glucose storage. Finally, a series of related studies indicated that the magnitude and nature of the inflammatory response in vivo could be enhanced by exogenous insulin infusion, indicating links between the hormone systems involved in intermediary metabolism and the inflammatory response. These findings have significant implications for the optimal design of feeding regimens for critically ill patients.
Notes: 0035-8843
Lectures
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15005922
Author Address: Department of Surgery, University of Manchester, Hope Hospital, Salford M6 8HD, UK. gcarlson@fs1.ho.man.ac.uk

Reference Type: Journal Article
Record Number: 71
Author: Bessey, P. Q.; Lowe, K. A.
Year: 1993
Title: Early hormonal changes affect the catabolic response to trauma
Journal: Ann Surg
Volume: 218
Issue: 4
Pages: 476-89; discussion 489-91
Date: Oct
Accession Number: 8215639
Keywords: Adult
Amino Acids/metabolism
Blood Glucose/*metabolism
Calorimetry
Epinephrine/*metabolism
Female
Glucagon/*metabolism
Human
Hydrocortisone/*metabolism
Insulin/*metabolism
Lactates/metabolism
Lactic Acid
Male
Nitrogen/metabolism
Octreotide/metabolism
Potassium/metabolism
Sodium/metabolism
Support, U.S. Gov't, P.H.S.
Wounds and Injuries/*metabolism
Abstract: OBJECTIVE: The authors sought to determine how temporary insulin suppression might alter the catabolic effects of cortisol, glucagon, and epinephrine. SUMMARY BACKGROUND DATA: The metabolic responses to injury include hypermetabolism, accelerated net skeletal muscle protein breakdown, glucose intolerance, and insulin resistance. These alterations are associated with increased stress hormone concentrations. Insulin elaboration is usually suppressed immediately after an injury but is abundant later during convalescence. An infusion of hydrocortisone, glucagon, and epinephrine increases both stress hormone concentrations and insulin levels. It induces many of the metabolic alterations seen in critically ill patients, but it does not affect net muscle breakdown. METHODS: Seven healthy adults received a stress hormone infusion for 3 days in two separate studies. During one study they, also received an infusion of the somatostatin analogue, octreotide (0.005 micrograms/kg/min), to suppress insulin elaboration for the first 24 hours. During the other study (control), insulin was permitted to rise unchecked. RESULTS: Stress hormone concentrations, hypermetabolism (+/- 20% above basal), and leukocytosis were similar during both study periods. When insulin elaboration was temporarily suppressed, whole-body nitrogen loss was increased during the first 48 hours, and the efflux of amino acids from the forearm after 72 hours of infusion was 60% greater than the control level. CONCLUSIONS: Temporary insulin suppression during physiologic increases in stress hormone concentrations amplified whole-body nitrogen loss and led to the development of accelerated net skeletal muscle protein breakdown. Early hormonal changes after an injury may affect the development of later catabolic responses.
Notes: 0003-4932
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8215639
Author Address: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

Reference Type: Journal Article
Record Number: 72
Author: Essen, P.; Thorell, A.; McNurlan, M. A.; Anderson, S.; Ljungqvist, O.; Wernerman, J.; Garlick, P. J.
Year: 1995
Title: Laparoscopic cholecystectomy does not prevent the postoperative protein catabolic response in muscle
Journal: Ann Surg
Volume: 222
Issue: 1
Pages: 36-42
Date: Jul
Accession Number: 7618966
Keywords: Adult
Cholecystectomy
*Cholecystectomy, Laparoscopic
Comparative Study
Female
Human
Insulin Resistance
Male
Muscle Proteins/*biosynthesis
Muscle, Skeletal/*metabolism
Abstract: OBJECTIVE: The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity. SUMMARY BACKGROUND DATA: Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected. METHODS: Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity. RESULTS: The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%). CONCLUSIONS: Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.
Notes: 0003-4932
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7618966
Author Address: Department of Anesthesiology, Huddinge University Hospital, Sweden.

Reference Type: Journal Article
Record Number: 55
Author: Jeschke, M. G.; Klein, D.; Herndon, D. N.
Year: 2004
Title: Insulin treatment improves the systemic inflammatory reaction to severe trauma
Journal: Ann Surg
Volume: 239
Issue: 4
Pages: 553-60
Date: Apr
Accession Number: 15024317
Keywords: Acute-Phase Reaction/immunology
Burns/complications/*drug therapy/*immunology
Child
Child, Preschool
Critical Illness
Cytokines/blood/immunology
Female
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Male
Nutritional Status/physiology
Retrospective Studies
Sepsis Syndrome/*drug therapy/etiology/*immunology
Abstract: OBJECTIVE: Determine the effect of insulin on the systemic inflammatory response, pro- and anti-inflammatory cytokines and hepatic acute-phase-response in severely burned pediatric patients. SUMMARY BACKGROUND DATA: The systemic inflammatory and hepatic acute-phase-response contribute to hypermetabolism, multi-organ failure, and mortality. Insulin has been recently shown to decrease mortality and to prevent the incidence of multi-organ failure in critically ill patients; however, the underlying mechanisms have not been defined. METHODS: Thirteen thermally injured children received insulin to maintain blood glucose at a range from 120 to 180 mg/dl, 15 children received no insulin with blood glucose levels also at range from 120 to 180 mg/dl and served as controls. Our outcome measures encompassed the effect of insulin on pro-inflammatory mediators, the hepatic acute-phase-response, fat, and the IGF-I system. RESULTS: Insulin administration decreased pro-inflammatory cytokines and proteins, while increasing constitutive-hepatic proteins (P < 0.05). Burned children receiving insulin required significantly less albumin substitution to maintain normal levels compared with control (P < 0.05). Insulin decreased free fatty acids and serum triglycerides when compared with controls (P < 0.05). Serum IGF-I and IGFBP-3 significantly increased with insulin administration (P < 0.05). CONCLUSION: Insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.
Notes: 0003-4932
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15024317
Author Address: Klinik und Poliklinik fur Chirurgie, Klinikum der Universitat Regensburg, Germany. Mcjeschke@hotmail.com

Reference Type: Journal Article
Record Number: 2
Author: Klein, D.; Schubert, T.; Horch, R. E.; Jauch, K. W.; Jeschke, M. G.
Year: 2004
Title: Insulin treatment improves hepatic morphology and function through modulation of hepatic signals after severe trauma
Journal: Ann Surg
Volume: 240
Issue: 2
Pages: 340-9
Date: Aug
Accession Number: 15273560
Abstract: OBJECTIVE: The purpose of the present study was to determine the effect of insulin therapy on hepatic function, structure, and hepatic mRNA and protein cytokine expression during the hypermetabolic cascade post burn. SUMMARY BACKGROUND DATA: Liver function and morphology are crucial for survival of patients suffering from trauma, operations, or infections. Insulin decreased mortality and prevented the incidence of multiorgan failure in critically ill patients. METHODS: Rats received a thermal injury and were randomly divided into the insulin or control group. Our outcome measures encompassed the effect of insulin on hepatic proteins, hepatic pro- and anti-inflammatory cytokines mRNA and proteins, hepatocyte proliferation, including Bcl-2 and hepatocyte apoptosis, with caspases-3 and caspases-9. RESULTS: Insulin significantly improved hepatic protein synthesis by increasing albumin and decreasing c-reactive protein and fat (P < 0.05). Insulin decreased the hepatic inflammatory response signal cascade by decreasing hepatic pro-inflammatory cytokines mRNA and proteins IL-1beta and tumor necrosis factor at pretranslational levels. Insulin increased hepatic cytokine mRNA and protein expression of IL-2 and IL-10 at a pretranslational level when compared with controls (P < 0.05). Insulin increased hepatocyte proliferation along with Bcl-2 concentration, while decreasing hepatocyte apoptosis along with decreased caspases-3 and -9 concentration, thus improving liver morphology (P < 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring hepatic homeostasis, which has been shown to be critical for organ function and survival of critically ill patients.
Notes: 0003-4932
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15273560
Author Address: Klinik und Poliklinik fur Chirurgie, Klinikum der Universitat Regensburg, Germany.

Reference Type: Journal Article
Record Number: 25
Author: Mizock, B. A.
Year: 2001
Title: Alterations in fuel metabolism in critical illness: hyperglycaemia
Journal: Best Pract Res Clin Endocrinol Metab
Volume: 15
Issue: 4
Pages: 533-51
Date: Dec
Accession Number: 11800522
Keywords: Animals
Carbohydrates/metabolism
*Critical Illness
*Energy Metabolism
Glucose/metabolism
Human
Hyperglycemia/etiology/*metabolism/therapy
Stress/blood/metabolism
Abstract: Hyperglycaemia is common during critical illness and may be viewed teleologically as a means of ensuring an adequate supply of glucose for the brain and phagocytic cells. Under normal conditions, euglycaemia is maintained by neural, hormonal and hepatic autoregulatory mechanisms. Critical illness promotes hyperglycaemia through an activation of the hypothalamic-pituitary-adrenal axis, which in turn increases hepatic glucose production and inhibits insulin-mediated glucose uptake to skeletal muscle. Sustained hyperglycaemia is associated with adverse consequences that demand its control. Appropriate management includes discontinuing causative drugs, correcting hypokalaemia, treating infection and administering insulin. Insulin therapy also appears to be useful for promoting an anabolic response in skeletal muscle.
Notes: 1521-690x
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11800522
Author Address: Medical Intensive Care Unit, Department of Medicine, Cook County Hospital, 1835 West Harrison Street, Chicago, Illinois 60612, USA.

Reference Type: Book Section
Record Number: 54
Author: Löffler, G.
Year: 1998
Title: Insulin: Struktur, Biosynthese und Sekretion.
Book Title: Biochemie und Pathobiochemie
Publisher: Springer Verlag Berlin
Pages: 788-93
Edition: 6

Reference Type: Journal Article
Record Number: 26
Author: Thorell, A.; Efendic, S.; Gutniak, M.; Haggmark, T.; Ljungqvist, O.
Year: 1994
Title: Insulin resistance after abdominal surgery
Journal: Br J Surg
Volume: 81
Issue: 1
Pages: 59-63
Date: Jan
Accession Number: 8313123
Keywords: Adult
Blood Glucose/metabolism
*Cholecystectomy
Female
Human
Insulin/metabolism
*Insulin Resistance
Male
Middle Aged
Postoperative Period
Support, Non-U.S. Gov't
Abstract: A study was carried out to determine the time course and degree of postoperative insulin resistance in patients undergoing elective abdominal surgery. Mean(s.e.m.) insulin sensitivity was determined before and on the first (n = 10), fifth, ninth and 20th (n = 5) days after elective open cholecystectomy using the normoglycaemic (4.7(0.1) mmol/l), hyperinsulinaemic (402(12)pmol/l) glucose clamp technique. Preoperative insulin sensitivity expressed as the M value varied from 2.3 to 8.2 mg per kg per min. The relative reduction in insulin sensitivity was most pronounced on the first day after surgery, at a mean(s.e.m.) of 54(2) per cent. Thereafter, a large variation between individuals was found during the course of recovery, and insulin sensitivity returned to normal 20 days after operation. On the first day after surgery, plasma concentrations of glucose, C peptide, noradrenaline and glucagon were slightly but significantly higher than before operation (P < 0.05), whereas insulin, growth hormone, cortisol and adrenaline levels were unaltered. Marked insulin resistance thus develops after elective upper abdominal surgery and persists for at least 5 days after operation. Factors other than simultaneous changes in levels of the hormones studied seem to regulate the maintenance of postoperative insulin resistance.
Notes: 0007-1323
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8313123
Author Address: Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.

Reference Type: Journal Article
Record Number: 31
Author: Jauch, K. W.
Year: 1997
Title: Chirurgischer Metabolismus
Journal: Chirurg
Volume: 68
Issue: 6
Pages: 551-8
Date: Jun
Accession Number: 9324431
Keywords: Energy Metabolism/*physiology
English Abstract
Human
Nutritional Requirements
*Parenteral Nutrition
Postoperative Complications/*physiopathology/therapy
Sepsis Syndrome/*physiopathology/therapy
Abstract: Trauma, operative interventions, infection and other disturbances of homeostasis lead to a uniform reaction of the body, namely release and activation of hormones and cytokines. Profound alterations of substrate flow result, with mobilization of energy stores and degradation of structural and functional proteins of vital organs like the gut mucosa. Due to these reactions the energy demands of the organs are met and energy-consuming synthesis of substrates is indicated. Clinically, hypermetabolism, hyperglycemia, lipolysis and increased urea production with negative nitrogen balance can be observed. The metabolic reactivity is reached by an increased substrate cycling. To avoid negative consequences such as organ dysfunction, a rational situation-adapted substrate supply is warranted as well as reduction of catabolic stimuli and stimulation of anabolic factors. The metabolic care of the surgical patient is still a basic and important task.
Notes: 0009-4722
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9324431
Author Address: Klinik und Poliklinik fur Chirurgie, Universitat Regensburg.

Reference Type: Journal Article
Record Number: 27
Author: Malmberg, K.; Norhammar, A.; Wedel, H.; Ryden, L.
Year: 1999
Title: Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study
Journal: Circulation
Volume: 99
Issue: 20
Pages: 2626-32
Date: May 25
Accession Number: 10338454
Keywords: Aged
Biological Markers
Diabetes Mellitus/*complications/metabolism/*mortality
Female
Glucose/*metabolism
*Hospitalization
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Longitudinal Studies
Male
Middle Aged
Multivariate Analysis
Myocardial Infarction/*complications/*mortality/therapy
Risk Factors
Support, Non-U.S. Gov't
Thrombolytic Therapy
Abstract: BACKGROUND: The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). METHODS AND RESULTS: Of 620 diabetic patients with AMI, 306 were randomly assigned to a >/=24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and beta-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died (P=0. 011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb AIc were independent predictors of mortality in the total cohort, whereas previous AMI, hypertension, smoking, or female sex did not add independent predictive value. Metabolic control, mirrored by blood glucose and Hb AIc, improved significantly more in patients on intensive insulin treatment than in the control group. beta-Blockers improved survival in control subjects, whereas thrombolysis was most efficient in the intensive insulin group. CONCLUSIONS: Mortality in diabetic patients with AMI is predicted by age, previous heart failure, and severity of the glycometabolic state at admission but not by conventional risk factors or sex. Intensive insulin treatment reduced long-term mortality despite high admission blood glucose and Hb AIc.
Notes: 1524-4539
Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10338454
Author Address: Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.

Reference Type: Journal Article
Record Number: 20
Author: Johan Groeneveld, A. B.; Beishuizen, A.; Visser, F. C.
Year: 2002
Title: Insulin: a wonder drug in the critically ill?
Journal: Crit Care
Volume: 6
Issue: 2
Pages: 102-5
Date: Apr
Accession Number: 11983030
Keywords: Animals
*Critical Care
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Insulin-Like Growth Factor I/drug effects
Rats
Abstract: Stress hyperglycaemia is a common event in acute critical illness. There is increasing evidence that maintaining normoglycaemia and treatment with insulin (or with glucose-insulin-potassium [GIK]), even in non-diabetic persons, is helpful in limiting organ damage after myocardial infarction, stroke, traumatic brain injury and other conditions, even though the conditions may be accompanied by insulin resistance. A landmark study now suggests that maintaining normoglycaemia with intensive insulin treatment in a heterogeneous population of critically ill patients decreases morbidity and mortality. The potential mechanisms that underlie such a beneficial effect are discussed.
Notes: 1364-8535
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11983030
Author Address: Department of Intensive Care, Institute of Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. johan.groeneveld@vumc.nl

Reference Type: Journal Article
Record Number: 81
Author: McCowen, K. C.; Malhotra, A.; Bistrian, B. R.
Year: 2001
Title: Stress-induced hyperglycemia
Journal: Crit Care Clin
Volume: 17
Issue: 1
Pages: 107-24
Date: Jan
Accession Number: 11219223
Keywords: Glucose/metabolism
Human
Hyperglycemia/complications/epidemiology/*etiology/physiopathology/prevent
ion & control
Insulin/therapeutic use
Insulin Resistance
Intensive Care Units
Risk Factors
Stress/*complications
Abstract: Stress hyperglycemia is common and likely to be associated with at least some of the same complications as hyperglycemia in true diabetes mellitus, such as poor wound healing and a higher infection rate. The predominant cause is the intense counterregulatory hormone and cytokine responses of critical illness, often compounded by excessive dextrose administration, usually as TPN. Although randomized data suggesting benefit of controlling hyperglycemia in hospitalized patients are paltry, prospective controlled trials are feasible and should be initiated. In the interim, the practice at the authors' institution is to use insulin to lower plasma glucose concentrations to a safe range of 150 mg/dL to 200 mg/dL in all patients.
Notes: 0749-0704
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11219223
Author Address: Departments of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. KMcCowen@caregroup.harvard.edu

Reference Type: Journal Article
Record Number: 80
Author: Van den Berghe, G.
Year: 2002
Title: Neuroendocrine pathobiology of chronic critical illness
Journal: Crit Care Clin
Volume: 18
Issue: 3
Pages: 509-28
Date: Jul
Accession Number: 12140911
Keywords: *Chronic Disease
*Critical Illness
Hypothalamo-Hypophyseal System/physiopathology
Neurosecretory Systems/*physiopathology
Pituitary-Adrenal System/physiopathology
Somatotropin-Releasing Hormone/physiology
Stress/physiopathology
Support, Non-U.S. Gov't
Thyroid Gland/physiopathology
Thyroid Hormones/secretion
Abstract: The neuroendocrine stress response is a dynamic process involving multiple hormonal alterations with distinct features in the acute and chronic phase of critical illness. In the initial response to an acute stress event, the anterior pituitary actively releases its hormones into the circulation while in the periphery, anabolic target organ hormones are inactivated. This response is thought to be beneficial and adaptive. When critical illness becomes prolonged, pulsatile secretion of anterior pituitary hormones becomes uniformly reduced due to reduced (hypothalamic) stimulation, and this underlies reduced activity of the respective target tissues and impaired anabolism. This difference in the acute and chronic stress response may not be trivial. It was the (inappropriate) assumption that acute stress responses, such as GH resistance, persist throughout the course of critical illness, which had formed the (inappropriate) justification to administer high doses of GH to long-stay intensive care patients to induce anabolism [102]. The concomitant endocrine changes in chronic critical illness may have predisposed to severe side effects of high doses of GH. In view of the significant benefits of strict glycemic control using exogenous insulin recently demonstrated in ICU patients [101], GH-induced insulin resistance and hyperglycemia may have played a role. It remains to be studied whether endocrine intervention with releasing factors such as TRH and GHRP in prolonged critical illness will accelerate recovery of patients who have entered the vicious circle of prolonged intensive care dependency.
Notes: 0749-0704
Journal Article
Review
Review, Academic
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12140911
Author Address: Department of Intensive Care Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.be

Reference Type: Journal Article
Record Number: 12
Author: Bertolini, G.; Latronico, N.; Brazzi, L.; Radrizzani, D.
Year: 2003
Title: Insulin dose or glycemic control for the critically ill?
Journal: Crit Care Med
Volume: 31
Issue: 10
Pages: 2565-6; author reply 2566
Date: Oct
Accession Number: 14530775
Keywords: Blood Glucose/*drug effects
*Critical Care
Human
Insulin/physiology/*therapeutic use
Notes: 0090-3493
Comment
Letter
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14530775

Reference Type: Journal Article
Record Number: 28
Author: Bone, R. C.
Year: 1996
Title: Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation
Journal: Crit Care Med
Volume: 24
Issue: 1
Pages: 163-72
Date: Jan
Accession Number: 8565523
Keywords: Animals
Cytokines/*physiology
Human
Interleukins/physiology
Multiple Organ Failure/physiopathology
Sepsis Syndrome/*physiopathology
Tumor Necrosis Factor/physiology
Abstract: OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is the massive inflammatory reaction resulting from systemic mediator release that may lead to multiple organ dysfunction. The objective of this review article is to analyze the roles of cytokines, cytokine production, and the relationship of cytokine production to the development of SIRS. DATA SOURCES: Previous research and clinical studies related to cytokines and their relationship to SIRS. STUDY SELECTION: From the studies reviewed, three critical questions are addressed. First, what is the definition of increased cytokine concentrations? Second, what other systemic illnesses besides sepsis can alter cytokine concentrations? Third, what are the right cytokines to measure? DATA SYNTHESIS: This article postulates a three-stage development of SIRS, in which stage 1 is a local production of cytokines in response to an injury or infection. Stage 2 is the protective release of a small amount of cytokines into the body's circulation. Stage 3 is the massive systemic reaction where cytokines turn destructive by compromising the integrity of the capillary walls and flooding end organs. CONCLUSIONS: While cytokines are generally viewed as a destructive development in the patient that generally leads to multiple organ dysfunction, cytokines also protect the body when localized. It will be necessary to study the positive effects of cytokines while also studying their role in causing SIRS. It will also be important to investigate the relationship between cytokines and their blockers in SIRS.
Notes: 0090-3493
Journal Article
Review
Review, Academic
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8565523
Author Address: Medical College of Ohio, Toledo, USA.

Reference Type: Journal Article
Record Number: 7
Author: Coursin, D. B.; Connery, L. E.; Ketzler, J. T.
Year: 2004
Title: Perioperative diabetic and hyperglycemic management issues
Journal: Crit Care Med
Volume: 32
Issue: 4 Suppl
Pages: S116-25
Date: Apr
Accession Number: 15064670
Keywords: Acute Disease
Cardiovascular Diseases/complications/surgery
Diabetes Mellitus/complications/epidemiology/*surgery/therapy
Human
Hyperglycemia/complications/epidemiology/*prevention & control
Insulin/therapeutic use
Intensive Care/methods
Perioperative Care/*methods
Abstract: OBJECTIVE AND DESIGN: To review and discuss selected literature, expert opinion, and conventional care of the hyperglycemic perioperative or critically ill patient. MAIN POINTS: Diabetes mellitus, the most commonly encountered perioperative endocrinopathy, continues to increase dramatically in prevalence. Diabetes is the sixth most common cause of death in the United States and significantly affects other more common causes of death such as cardiac disease and stroke. Diabetic patients commonly have microvascular and macrovascular pathology that influences their perioperative course and critical illness and increases morbidity and mortality rates during hospitalization. Since diabetics require more surgeries and receive critical care more frequently than their nondiabetic counterparts, preemptive identification and anticipation of diabetic complications and comorbidities, along with an optimized treatment plan, are the foundation for the proper intensive care of this growing patient population. Hyperglycemia occurs commonly in critically ill diabetic patients but also is frequent in those who have a history of normal glucose homeostasis. The new onset of hyperglycemia in critically ill patients is driven by excessive counterregulatory stress hormone release and high tissue and circulating concentrations of inflammatory cytokines. Aggressive glycemic management improves short- and long-term outcomes in diabetic patients with acute myocardial infarction and cardiac surgical patients. Most recently, "tight" glycemic control in both diabetic and nondiabetic hyperglycemic intensive care unit patients resulted in improved survival in selected surgical patients without excessive consequences related to hypoglycemia. The mechanisms of benefit of euglycemia appear to be multifactorial. CONCLUSIONS: Up to 25% of patients admitted to the intensive care unit have previously diagnosed diabetes. Diabetics are most commonly admitted for treatment of complications of comorbid diseases. New-onset hyperglycemia also is common in critically ill patients, and it affects patient morbidity and mortality rates. A growing body of literature supports the benefits of tight glycemic control in certain patient populations. However, further data are needed about the optimal concentration of blood glucose, the role of maintaining euglycemia in a broader group of patients (including the medically critically ill), and the mechanisms of benefit of infused glucose and insulin.
Notes: 0090-3493
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15064670
Author Address: Anesthesiology and Medicine, University of Wisconsin-Madison, USA.

Reference Type: Journal Article
Record Number: 29
Author: Knaus, W. A.; Draper, E. A.; Wagner, D. P.; Zimmerman, J. E.
Year: 1985
Title: APACHE II: a severity of disease classification system
Journal: Crit Care Med
Volume: 13
Issue: 10
Pages: 818-29
Date: Oct
Accession Number: 3928249
Keywords: Acute Disease
Adult
Age Factors
Aged
Chronic Disease
Comparative Study
Coronary Artery Bypass/mortality
*Costs and Cost Analysis
Critical Care/*methods
*Diagnosis-Related Groups
Disease/*classification/physiopathology
Human
Middle Aged
Patient Admission
Prognosis
Risk
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Surgical Procedures, Operative/mortality
Abstract: This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases. When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.
Notes: 0090-3493
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3928249

Reference Type: Journal Article
Record Number: 56
Author: Shipman, J.; Guy, J.; Abumrad, N. N.
Year: 2003
Title: Repair of metabolic processes
Journal: Crit Care Med
Volume: 31
Issue: 8 Suppl
Pages: S512-7
Date: Aug
Accession Number: 12907880
Keywords: Acute-Phase Reaction/physiopathology
Autonomic Nervous System/physiopathology
Critical Illness/*therapy
Energy Metabolism/*physiology
Growth Hormone/blood
Homeostasis/*physiology
Human
Hypothalamo-Hypophyseal System/physiopathology
Inflammation Mediators/blood
Insulin/blood
Sepsis Syndrome/*physiopathology/therapy
Somatomedins/metabolism
T-Lymphocytes/immunology
Notes: 0090-3493
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12907880
Author Address: Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

Reference Type: Journal Article
Record Number: 17
Author: Van den Berghe, G.; Wouters, P. J.; Bouillon, R.; Weekers, F.; Verwaest, C.; Schetz, M.; Vlasselaers, D.; Ferdinande, P.; Lauwers, P.
Year: 2003
Title: Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control
Journal: Crit Care Med
Volume: 31
Issue: 2
Pages: 359-66
Date: Feb
Accession Number: 12576937
Keywords: Blood Glucose/*analysis
Critical Illness/*therapy
Human
Insulin/*administration & dosage
Prospective Studies
Support, Non-U.S. Gov't
Treatment Outcome
Abstract: OBJECTIVES: Maintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients. Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits. DESIGN: A prospective, randomized, controlled trial. SETTING: A 56-bed predominantly surgical intensive care unit in a tertiary teaching hospital. PATIENTS AND INTERVENTION: A total of 1,548 patients were randomly assigned to either strict normalization of blood glucose (80-110 mg/dL) with insulin infusion or the conventional approach, in which insulin is only given to maintain blood glucose levels at 180-200 mg/dL. MEASUREMENTS AND MAIN RESULTS: It was feasible and safe to achieve and maintain blood glucose levels at <110 mg/dL by using a titration algorithm. Stepwise linear regression analysis identified body mass index, history of diabetes, reason for intensive care unit admission, at-admission hyperglycemia, caloric intake, and time in intensive care unit as independent determinants of insulin requirements, together explaining 36% of its variation. With nutritional intake increasing from a mean of 550 to 1600 calories/day during the first 7 days of intensive care, normoglycemia was reached within 24 hrs, with a mean daily insulin dose of 77 IU and maintained with 94 IU on day 7. Insulin requirements were highest and most variable during the first 6 hrs of intensive care (mean, 7 IU/hr; 10% of patients required >20 IU/hr). Between day 7 and 12, insulin requirements decreased by 40% on stable caloric intake. Brief, clinically harmless hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median day 6 (2-14) vs. 0.8% of conventionally treated patients on day 11 (2-10). The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding. Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality (p <.0001), critical illness polyneuropathy (p <.0001), bacteremia (p =.02), and inflammation (p =.0006) but not to prevention of acute renal failure, for which the insulin dose was an independent determinant (p =.03). As compared with normoglycemia, an intermediate blood glucose level (110-150 mg/dL) was associated with worse outcome. CONCLUSION: Normoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines. Metabolic control, as reflected by normoglycemia, rather than the infused insulin dose, was related to the beneficial effects of intensive insulin therapy.
Notes: 0090-3493
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12576937
Author Address: Department of Intensive Care Medicine, Catholic University of Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.be

Reference Type: Journal Article
Record Number: 6
Author: Solano, T.; Totaro, R.
Year: 2004
Title: Insulin therapy in critically ill patients
Journal: Curr Opin Clin Nutr Metab Care
Volume: 7
Issue: 2
Pages: 199-205
Date: Mar
Accession Number: 15075712
Keywords: Animals
Blood Glucose/metabolism
Critical Care/*methods
Critical Illness/*therapy
Glucose/administration & dosage
Human
Hyperglycemia/complications/*drug therapy/etiology
Hypoglycemic Agents/*therapeutic use
Insulin/administration & dosage/*therapeutic use
Intensive Care Units
Myocardial Infarction/physiopathology/therapy
Potassium/administration & dosage
Treatment Outcome
Abstract: PURPOSE OF REVIEW: The recent publication of the results of an aggressive approach to the treatment of hyperglycaemia in critically ill patients, and a rekindling of interest in the use of an infusion of glucose insulin and potassium as adjunctive therapy in a diverse group of patients with cardiovascular disease, warrants a review of the multiple effects of insulin and a review of laboratory and clinical studies. RECENT FINDINGS: The use of an aggressive protocol to maintain normoglycaemia in critically ill patients has been demonstrated to be a beneficial technique in the critical care setting. Implementation of the protocol outside of a research setting appears to be feasible. Recent studies on the use of insulin in addition to glucose and potassium in patients with diverse cardiovascular diseases have also demonstrated positive results. SUMMARY: This review will summarize some of the putative beneficial effects of insulin as a pharmacological agent, and review recent clinical data. Although the relative benefits of normoglycaemia in the critical care setting and the beneficial effects of insulin are difficult to differentiate, a substantial overlap exists. The extent to which these converging therapies (aggressive normoglycaemia and insulin pharmacotherapy) will be applicable to diverse clinical settings has yet to be determined.
Notes: 1363-1950
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15075712
Author Address: General Intensive Care Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. thomas.solano@email.cs.nsw.gov.au

Reference Type: Journal Article
Record Number: 14
Author: Das, U. N.
Year: 2003
Title: Insulin: an endogenous cardioprotector
Journal: Curr Opin Crit Care
Volume: 9
Issue: 5
Pages: 375-83
Date: Oct
Accession Number: 14508150
Keywords: Animals
Blood Glucose/*metabolism
Diabetic Ketoacidosis/drug therapy
Glucose/administration & dosage
Human
Hyperglycemia/complications/*drug therapy/physiopathology
Insulin/administration & dosage/*therapeutic use
Insulin Resistance
Macrophage Migration-Inhibitory Factors/metabolism
Myocardial Infarction/complications/drug therapy/*prevention & control
Nitric Oxide/metabolism
Potassium/administration & dosage
Shock, Septic/complications/drug therapy
Tumor Necrosis Factor/antagonists & inhibitors/metabolism
Abstract: This review discusses the myocardial protective property of the insulin/glucose-insulin-potassium regimen and the mechanisms involved in this beneficial action. Several recent studies suggest that insulin not only is useful to control hyperglycemia and maintain glucose homeostasis but also may have the unique property to protect the myocardium from reperfusion injury and ischemia and prevent apoptosis of myocardial cells. The insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha, interleukin-6, macrophage migration inhibitory factor and other pro-inflammatory cytokines, and free radicals; and enhances the synthesis of endothelial nitric oxide and anti-inflammatory cytokines interleukin-4 and interleukin-10. Thus, the insulin/GIK regimen brings about its cardioprotective action. This may also explain why the insulin/GIK regimen is useful in sepsis and septic shock, myocardial recovery in acute myocardial infarction, and critical illness. It is suggested that the infusion of adequate amounts of insulin to patients with acute myocardial infarction, congestive heart failure, cardiogenic shock, and critical illness preserves myocardial integrity and function and ensures rapid recovery. In view of the suppressive action of insulin on the synthesis of proinflammatory cytokines and free radicals, it is possible that the insulin/GIK regimen, when used in a timely and appropriate fashion, may also protect other tissues and organs and facilitate in the recovery of patients who are critically ill.
Notes: 1070-5295
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14508150
Author Address: EFA Sciences LLC, Norwood, Massachusetts 02062, USA. Undurti@hotmail.com

Reference Type: Journal Article
Record Number: 30
Author: Morris, A. H.
Year: 2003
Title: Treatment algorithms and protocolized care
Journal: Curr Opin Crit Care
Volume: 9
Issue: 3
Pages: 236-40
Date: Jun
Accession Number: 12771677
Keywords: *Algorithms
Blood Glucose/analysis
Carbon Monoxide Poisoning/therapy
Catheterization, Swan-Ganz/standards
*Clinical Protocols
Decision Support Techniques
Emergency Service, Hospital/standards
Human
Hyperbaric Oxygenation/standards
Hyperglycemia/drug therapy
Insulin/therapeutic use
Intensive Care/*standards
Positive-Pressure Respiration/standards
Practice Guidelines
Shock, Septic/therapy
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Abstract: PURPOSE OF REVIEW: Excess information in complex ICU environments exceeds human decision-making limits and likely contributes to unnecessary variation in clinical care, increasing the likelihood of clinical errors. I reviewed recent critical care clinical trials searching for information about the impact of protocol use on clinically pertinent outcomes. RECENT FINDINGS: Several recently published clinical trials illustrate the importance of distinguishing efficacy and effectiveness trials. One of these trials illustrates the danger of conducting effectiveness trials before the efficacy of an intervention is established. The trials also illustrate the importance of distinguishing guidelines and inadequately explicit protocols from adequately explicit protocols. Only adequately explicit protocols contain enough detail to lead different clinicians to the same decision when faced with the same clinical scenario. SUMMARY: Differences between guidelines and protocols are important. Guidelines lack detail and provide general guidance that requires clinicians to fill in many gaps. Computerized or paper-based protocols are detailed and, when used for complex clinical ICU problems, can generate patient-specific, evidence-based therapy instructions that can be carried out by different clinicians with almost no interclinician variability. Individualization of patient therapy can be preserved by these protocols when they are driven by individual patient data. Explicit decision-support tools (eg, guidelines and protocols) have favorable effects on clinician and patient outcomes and can reduce the variation in clinical practice. Guidelines and protocols that aid ICU decision makers should be more widely distributed.
Notes: 1070-5295
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12771677
Author Address: Department of Medicine, LDS Hospital and University of Utah School of Medicine, Salt Lake City, Utah 84143, USA. ldamorri@ihc.com

Reference Type: Journal Article
Record Number: 13
Author: Patel, G. P.; Gurka, D. P.; Balk, R. A.
Year: 2003
Title: New treatment strategies for severe sepsis and septic shock
Journal: Curr Opin Crit Care
Volume: 9
Issue: 5
Pages: 390-6
Date: Oct
Accession Number: 14508152
Keywords: Acute Disease
Adrenal Cortex Hormones/therapeutic use
Anti-Bacterial Agents/therapeutic use
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
Clinical Trials
Critical Care
Human
Hyperglycemia/drug therapy/prevention & control
Insulin/administration & dosage
Norepinephrine/therapeutic use
Prognosis
Protein C/therapeutic use
Recombinant Proteins/therapeutic use
Sepsis/epidemiology/mortality/*therapy
Shock, Septic/epidemiology/mortality/*therapy
Survival Rate
United States/epidemiology
Vasoconstrictor Agents/therapeutic use
Ventilators, Mechanical
Abstract: PURPOSE OF REVIEW: Severe sepsis and septic shock are common causes of morbidity and mortality in critically ill patients. The complexities of the septic cascade continue to emerge and may identify new targets for innovative patient management. This review will highlight some of the recent advances in our management of the patient with sepsis. RECENT FINDINGS: The early administration of adequate antibiotic therapy, effective source control, and goal-directed hemodynamic resuscitation are the cornerstone of successful management. Prevention of the complications of critical illness and maintenance of normal glucose levels are also important elements of effective management. In patients with vasopressor-dependent septic shock, evaluation for inadequate cortisol response and the provision of physiologic doses of replacement steroids for those found to be deficient may result in improved survival. Administration of drotrecogin alfa (activated), (activated protein C) has been shown to improve survival in patients with severe sepsis and septic shock who have a high risk of mortality. Because of its anticoagulant properties, caution must be exercised with the use of activated protein C in those patients who meet the contraindications for its use or who have risk factors for increased bleeding complications. SUMMARY: Significant advances have been made in our understanding of the septic cascade and our ability to manage patients with severe sepsis and septic shock. Despite these advances, significant morbidity and mortality continue. In addition, there is also considerable impact on the financial and overall function of the patient.
Notes: 1070-5295
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14508152
Author Address: Section of Pharmacy Services, Department of Medicine, Rush Medical College, Chicago, Illinois, USA.

Reference Type: Journal Article
Record Number: 58
Author: Trager, K.; DeBacker, D.; Radermacher, P.
Year: 2003
Title: Metabolic alterations in sepsis and vasoactive drug-related metabolic effects
Journal: Curr Opin Crit Care
Volume: 9
Issue: 4
Pages: 271-8
Date: Aug
Accession Number: 12883281
Keywords: Adrenergic Agonists/*therapeutic use
Catecholamines/*therapeutic use
*Critical Illness
Energy Metabolism/*drug effects
Epoprostenol/therapeutic use
Glucose/metabolism
Human
Lactates/metabolism
Mitochondria/physiology
Sepsis/*metabolism/physiopathology
Vasopressins/therapeutic use
Abstract: The main clinical characteristics of sepsis and septic shock are derangements of cardiocirculatory and respiratory function. Additionally, profound alterations in metabolic pathways occur leading to hypermetabolism, enhanced energy expenditure, and insulin resistance. The clinical hallmarks are hyperglycemia, hyperlactatemia, and enhanced protein catabolism. These metabolic alterations are even more pronounced during sepsis as a result of cytokine release and subsequent induction of inflammatory pathways. Increased oxygen demands from mitochondrial oxygen utilization and oxygen consumption related to oxygen radical formation may contribute to hypermetabolism. In addition, mitochondrial dysfunction with impaired cellular respiration may be present. Mainstay therapeutic interventions for hemodynamic stabilization are adequate volume resuscitation and vasoactive agents, which, however, have additional impact on metabolic activity. Therefore, beyond hemodynamic effects, specific drug-related metabolic alterations need to be considered for optimal treatment during sepsis. This review gives an overview of the typical metabolic alterations during sepsis and septic shock and highlights the impact of vasoactive therapy on metabolism.
Notes: 1070-5295
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12883281
Author Address: Klinik fur Anasthesiologie, Universitatsklinikum Ulm, Germany. karl.traeger@medizin.uni-ulm.de

Reference Type: Journal Article
Record Number: 32
Author: Heinemann, L.; Chantelau, E. A.; Starke, A. A.
Year: 1992
Title: Pharmacokinetics and pharmacodynamics of subcutaneously administered U40 and U100 formulations of regular human insulin
Journal: Diabete Metab
Volume: 18
Issue: 1
Pages: 21-4
Date: Jan-Feb
Accession Number: 1563532
Keywords: Adult
Blood Glucose/metabolism
C-Peptide/blood
Comparative Study
Dosage Forms
Glucose Clamp Technique
Human
Injections, Subcutaneous
Insulin/administration & dosage/*pharmacokinetics/pharmacology
Male
Time Factors
Abstract: Action profiles of 12 U of regular human insulin (Actrapid HM) administered subcutaneously as a U40 or U100 formulation were studied. Euglycaemic glucose clamps were performed on two separate days in 8 healthy subjects (basal i.v. insulin infusion 0.1 mU/kg/min, plasma glucose 5.0 mmol/l, mean +/- SD age 25 +/- 2 years, BMI 22.7 +/- 1.4 kg/m2). Serum insulin concentrations increased after injection of U40 or U100 from similar baseline values to maximal individual concentrations of 305 +/- 79 vs. 285 +/- 62 pmol/l (NS) after 90 +/- 33 vs. 114 +/- 58 min (NS). Ten, 15, and 20 min post injection insulin concentrations were significantly higher by an average of 30 pmol/l after U40 insulin vs. U100 insulin (p less than 0.05). Glucose infusion rates increased from comparable baseline rates to maximal individual glucose infusion rates of 10.7 +/- 2.4 vs. 10.9 +/- 3.0 mg/kg/min (NS) after 172 +/- 51 vs. 169 +/- (39) min (NS). At the three time points when significantly different serum insulin concentrations occurred soon after insulin injection, glucose infusion rates were not significantly different between U40 and U100. Although small differences in insulin pharmacokinetics were detected early after s.c. insulin injection (U40 was absorbed faster than U100 insulin) the pharmacodynamics of the U40 and U100 formulation of regular human insulin appear to be comparable in healthy subjects.
Notes: 0338-1684
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1563532
Author Address: Department of Nutrition and Metabolic Diseases, Heinrich-Heine-University of Dusseldorf, Germany.

Reference Type: Journal Article
Record Number: 33
Author: Heinemann, L.; Richter, B.
Year: 1993
Title: Clinical pharmacology of human insulin
Journal: Diabetes Care
Volume: 16 Suppl 3
Pages: 90-100
Date: Dec
Accession Number: 8299482
Keywords: Animals
Blood Glucose/drug effects/metabolism
Comparative Study
Diabetes Mellitus, Type I/blood/drug therapy
Glucose Clamp Technique
Human
Insulin/administration & dosage/*pharmacokinetics/*pharmacology
Insulin, Isophane/pharmacokinetics/pharmacology
Insulin, Lente/pharmacokinetics/pharmacology
Lipids/metabolism
Recombinant Proteins/administration &
dosage/*pharmacokinetics/*pharmacology
Swine
Time Factors
Abstract: Nowadays, human insulin is used daily by millions of diabetic patients. The biological effect of human insulin is comparable to that of porcine insulin. However, after subcutaneous injection, pharmacological and clinical studies showed pharmacokinetic and pharmacodynamic differences between human and animal insulins. Human insulin tends to have faster absorption and shorter duration of action compared with animal insulin. These differences are more pronounced and can be of clinical relevance with intermediate- and long-acting insulin preparations. Optimal metabolic control can be achieved with either human or highly purified animal insulin preparations, provided appropriate insulin replacement strategies are used.
Notes: 0149-5992
Journal Article
Review
Review, Academic
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8299482
Author Address: Department of Nutrition and Metabolic Diseases (WHO Collaborating Center for Diabetes), Heinrich-Heine-University of Dusseldorf, Germany.

Reference Type: Journal Article
Record Number: 34
Author: Schranz, D. B.; Lernmark, A.
Year: 1998
Title: Immunology in diabetes: an update
Journal: Diabetes Metab Rev
Volume: 14
Issue: 1
Pages: 3-29
Date: Mar
Accession Number: 9605628
Keywords: Allergy and Immunology/trends
Animals
Autoantibodies/immunology
Autoantigens/immunology
Autoimmunity/immunology
Diabetes Mellitus, Type I/etiology/genetics/*immunology
Human
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Abstract: Type 1 (insulin-dependent) diabetes mellitus is strongly associated with autoimmune phenomena connected to the loss of beta-cells in the pancreatic islets. Despite considerable progress in our understanding of genetic susceptibility factors and islet autoimmunity preceding the clinical onset of Type 1 diabetes there are considerable gaps in our knowledge. First, the etiology is unclear. It is speculated that multiple etiological factors may initiate a common pathogenic pathway which results in immune-mediated beta-cell destruction. In 1998 we will need to learn more about the possible importance of gestational infections, as well as isolation of viral DNA or RNA from the blood of new-onset patients or marker-positive individuals. The scan of the whole genome has provided a smorgasbord of genetic regions which confer diabetes risk either alone or in combination. HLA remains the major genetic risk factor, and while HLA peptide binding information is considerable, we understand less of autoantigen processing and presentation. Cloned autoantigens and their use in standardized autoantibody assays have improved our ability to identify individuals at risk for diabetes. The diagnostic sensitivity and specificity of autoantibody markers for Type 1 diabetes are high as are their predictive values. We need methods to combine autoantibodies with genetic risk factors. The identification of individuals in different stages of their pathogenesis, including patients with so-called slowly progressive Type 1 diabetes (SPIDDM, LADA etc.), allow approaches to novel therapeutic interventions. Insulin is currently the therapeutic agent of choice and although spontaneous insulin-dependent diabetes in the NOD mouse and the BB rat can be prevented by immune suppression or modulation, this has not yet been possible in humans. The 1998 research on the interaction between environmental factors and susceptibility genes to initiate beta-cell specific autoreactivity should allow the development of therapies for prevention, and perhaps a cure, of insulin-dependent (Type 1) diabetes.
Notes: 0742-4221
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9605628
Author Address: Department of Medicine, University of Washington, Seattle 98195-7710, USA.

Reference Type: Book Section
Record Number: 53
Author: Hepp, K. D.; Häring, H. U.
Year: 2003
Title: Einführung in die Biochemie und Pathophysiologie des Stoffwechsels
Book Title: Diabetologie in Klinik und Praxis
Publisher: Thieme Verlag Stuttgart
Pages: 1-42
Edition: 5

Reference Type: Journal Article
Record Number: 16
Author: Mesotten, D.; Van den Berghe, G.
Year: 2003
Title: Clinical potential of insulin therapy in critically ill patients
Journal: Drugs
Volume: 63
Issue: 7
Pages: 625-36
Accession Number: 12656643
Keywords: *Critical Care
*Critical Illness
Diabetes Mellitus/complications
Human
Hyperglycemia/*drug therapy/etiology
Hypoglycemic Agents/administration & dosage/*pharmacology
Insulin/administration & dosage/*pharmacology
Intensive Care Units
Nutritional Support
Prognosis
Support, Non-U.S. Gov't
Abstract: Stress of critical illness is often accompanied by hyperglycaemia, whether or not the patient has a history of diabetes mellitus. This has been considered to be part of the adaptive metabolic response to stress. The level of hyperglycaemia in patients with acute myocardial infarction (MI) or stroke upon admission to the hospital has been related to the risk of adverse outcome. However, until recently, there was no evidence of a causal relationship and thus stress-induced hyperglycaemia was only treated with exogenous insulin when it exceeded 12 mmol/L (220 mg/dL). In patients with known diabetes, even higher levels were often tolerated. Recently, new data became available in support of another approach. In this review, we focus on the new evidence and the clinical aspects of managing hyperglycaemia with insulin in critically ill patients, drawing a parallel with diabetes management. Particularly, the 'Diabetes and Insulin-Glucose infusion in Acute Myocardial Infarction (DIGAMI) study' and the 'insulin in intensive care study' have provided novel insights. The DIGAMI study showed that in patients with diabetes, controlling blood glucose levels below 12 mmol/L for 3 months after acute MI improves long-term outcome. In the recent study of predominantly surgical intensive care patients, the majority of whom did not previously have diabetes, it was shown that an even tighter control of blood glucose with exogenous insulin, aiming for normoglycaemia, dramatically improved outcome. Indeed, in this large prospective, randomised, controlled study, 1548 intensive care patients had been randomly allocated to either the conventional approach, with insulin infusion started only when blood glucose levels exceeded 12 mmol/L, or intensive insulin therapy, with insulin infused to maintain blood glucose at a level of 4.5-6.1 mmol/L (80-110 mg/dL). Intensive insulin therapy reduced intensive care mortality by more than 40% and also decreased a number of morbidity factors including acute renal failure, polyneuropathy, ventilator-dependency and septicaemia. Future studies will be needed to further unravel the mechanisms that explain the beneficial effects of this simple and cost-saving intervention. Although available evidence supports implementation of intensive insulin therapy in surgical intensive care, the benefit for other patient populations, such as patients on medical intensive care units or hospitalised patients who do not require intensive care but who do present with stress-induced hyperglycaemia, remains to be investigated.
Notes: 0012-6667
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12656643
Author Address: Department of Intensive Care Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.

Reference Type: Journal Article
Record Number: 4
Author: Jeschke, M. G.; Klein, D.; Bolder, U.; Einspanier, R.
Year: 2004
Title: Insulin attenuates the systemic inflammatory response in endotoxemic rats
Journal: Endocrinology
Date: Jun 10
Accession Number: 15192048
Abstract: Insulin decreases the mortality and prevents the incidence of infection and sepsis in critically ill patients. The molecular and cellular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin on the inflammatory reaction during endotoxemia. Endotoxemic rats were randomly divided into two groups to receive either saline or insulin. The effect of insulin on hepatic signal transcription factor mRNA expression, pro-inflammatory and anti-inflammatory cytokine mRNA and protein concentration was determined. Insulin administration did not change glucose or electrolyte levels but significantly decreased pro-inflammatory signal transcription factors (C/EBPbeta, STAT-3 and-5, RANTES) and cytokine expression in the liver and serum levels of IL-1beta, IL-6, MIF and TNF-alpha. Insulin administration further decreased HMG-1 in the serum compared with controls. In addition, insulin increased anti-inflammatory cytokine expression in the liver and serum levels of IL-2, IL-4 and IL-10, and hepatic SOCS-3 mRNA expression. Insulin modulates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade. As glucose and electrolyte levels did not differ between insulin and control we hypothesize that the effects are direct anti-inflammatory mechanisms of insulin rather than indirect through modulation of glucose or electrolyte metabolism.
Notes: 0013-7227
Journal article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15192048
Author Address: Department of Surgery. Friedrich-Alexander University of Erlangen, Germany; Department of Surgery. University of Regensburg, Germany; Institute of Veterinary Biochemistry, Free University Berlin, Germany.

Reference Type: Journal Article
Record Number: 60
Author: Ma, Y.; Toth, B.; Keeton, A. B.; Holland, L. T.; Chaudry, I. H.; Messina, J. L.
Year: 2004
Title: Mechanisms of Hemorrhage-induced Hepatic Insulin Resistance: Role of Tumor Necrosis Factor alpha
Journal: Endocrinology
Date: Aug 5
Accession Number: 15297437
Abstract: Hemorrhage, sepsis, burn injury, surgical trauma and critical illness all induce insulin resistance. Recently, we found that trauma and hemorrhage acutely induced hepatic insulin resistance in the rat. However, the mechanisms of this hemorrhage-induced acute hepatic insulin resistance are unknown. Here we report on the mechanisms of this hepatic insulin resistance. Protein levels and phosphorylation of the insulin receptor and of insulin receptor substrate-1/2 (IRS-1/2) were measured, as was the association between IRS-1/2 and phosphatidylinositol 3-kinase (PI3K). Also examined were the hepatic expression of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha-induced serine phosphorylation of IRS-1. Insulin receptor and IRS-1/2 protein levels, and insulin-induced tyrosine phosphorylation of the insulin receptor were unaltered. In contrast, insulin-induced tyrosine phosphorylation of IRS-1/2 and association between IRS-1/2 and PI3K were dramatically reduced following hemorrhage. Hepatic levels of TNF-alpha mRNA and protein were increased as was phosphorylation of IRS-1 serine 307 following hemorrhage. Our data provide the first evidence that compromised IRS-1/2 tyrosine phosphorylation and their association with PI3K contribute to hemorrhage-induced acute hepatic insulin resistance. Increased local TNF-alpha may play a role in inducing this hepatic insulin resistance following trauma and hemorrhage.
Notes: 0013-7227
Journal article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15297437
Author Address: Department of Pathology, Division of Molecular and Cellular Pathology, Center for Surgical Research and Department of Surgery, The University of Alabama at Birmingham, Birmingham AL, 35294.

Reference Type: Generic
Record Number: 52
Author: Powers, A. C.
Year: 2004
Title: Diabetes mellitus
Secondary Title: Harrison's internal medicine
Publisher: The McGraw-Hill Companies
Number: 13.08.
Date: 06.08.04
Type of Work: Web Site
URL: http://harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch333/ch333_p01.html

Reference Type: Journal Article
Record Number: 76
Author: Polonsky, K. S.; Sturis, J.; Van Cauter, E.
Year: 1998
Title: Temporal profiles and clinical significance of pulsatile insulin secretion
Journal: Horm Res
Volume: 49
Issue: 3-4
Pages: 178-84
Accession Number: 9550122
Keywords: Activity Cycles/physiology
Animals
Biological Clocks/*physiology
Diabetes Mellitus, Type II/physiopathology
Glucose Intolerance/physiopathology
Human
Insulin/*secretion
Islets of Langerhans/physiopathology
Abstract: In this article, recent experiments are reviewed which have addressed the role of oscillatory insulin secretion in the pathophysiology of glucose intolerance and diabetes. The ultradian oscillations of insulin secretion appear to be an integral part of the feedback loop between glucose and insulin secretion and as a result are abnormal in states of glucose intolerance. Treatment of impaired glucose tolerance with troglitazone, a thiazolidinedione that improves insulin sensitivity, leads to an improvement in the ability of the beta-cell to sense and respond to a glucose stimulus restoring the ability of glucose to entrain the ultradian oscillations. The rapid oscillations of insulin secretion appear to be an inherent feature of the cellular mechanisms of insulin secretion since they persist in the isolated perfused pancreas and in perifused islets. These oscillations are paralleled by changes in intracellular Ca2+ and are also abnormal in states of glucose intolerance and diabetes. Available evidence indicates that these alterations are due to decreased expression of voltage-dependent Ca2+ channels on the beta-cell membrane.
Notes: 0301-0163
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9550122
Author Address: Department of Medicine, University of Chicago, Pritzker School of Medicine, Ill 60637, USA.

Reference Type: Journal Article
Record Number: 35
Author: Hartl, W. H.; Jauch, K. W.
Year: 1994
Title: Postaggressionsstoffwechsel: Versuch einer Standortbestimmung
Journal: Infusionsther Transfusionsmed
Volume: 21
Issue: 1
Pages: 30-40
Date: Feb
Accession Number: 8173310
Keywords: Acute-Phase Reaction/metabolism
Critical Care/*methods
Energy Metabolism/*physiology
English Abstract
Homeostasis/physiology
Human
Nutritional Requirements
Parenteral Nutrition, Total/*methods
Postoperative Complications/*metabolism
Support, Non-U.S. Gov't
Abstract: OBJECTIVE: Selection of important results in pathophysiology and pathobiochemistry of the surgical patient. SOURCES: Anglo-American and German literature since 1988. SELECTION CRITERIA: Importance of reported results for the understanding of superior interactions. RESULTS: The term 'postaggression' syndrome was introduced on the basis of earlier observations regarding the pathophysiology of the surgical patient. More recent results which addressed pathobiochemistry, and which had been obtained by methods of molecular biology, led to the new definition as systemic inflammatory response syndrome (SIRS). Knowledge on metabolic changes which are associated with SIRS increased significantly in the field of protein and carbohydrate metabolism. Concerning the clinically important phenomenon of protein catabolism, it is possible today to differentiate between changes in protein synthesis and protein degradation. The time period which had passed since the underlying trauma and the variable responses of different organ systems were recognized as important variables of catabolism. The ongoing question regarding possible mediators of protein catabolism still remains unanswered. Release of cytokines which can be observed in SIRS appears to play only an indirect role. The small bowel, which is important for the general pathophysiology of SIRS, gained a central position in amino acid metabolism (especially glutamine metabolism). A new aspect of carbohydrate metabolism was found in the liver. The accelerated cycling of glucose molecules between glucose, glucose-6-phosphate, and glucose (glucose cycling) seems to contribute to the increased energy expenditure found in SIRS. CONCLUSIONS: Use of new methods in in vivo and in vitro research significantly expanded the knowledge on pathophysiological and pathobiochemical mechanisms in SIRS. Future research activities should tie together these individual mechanisms into the complex network as it presents to the physician during clinical routine.
Notes: 1019-8466
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8173310
Author Address: Chirurgische Klinik, Ludwig-Maximilians-Universitat, Munchen, BRD.

Reference Type: Journal Article
Record Number: 5
Author: Kanji, S.; Singh, A.; Tierney, M.; Meggison, H.; McIntyre, L.; Hebert, P. C.
Year: 2004
Title: Standardization of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults
Journal: Intensive Care Med
Volume: 30
Issue: 5
Pages: 804-10
Date: May
Accession Number: 15127193
Abstract: OBJECTIVE: Aggressive glycemic control improves mortality and morbidity in critically ill adults, however implementation of such a strategy can be logistically difficult. This study evaluates the efficiency and safety of a nurse-managed insulin protocol in critically ill adults. DESIGN: Combined retrospective-prospective before-after cohort study. SETTING: Twenty-one bed, medical/surgical ICU in a tertiary care hospital. PATIENTS: Two cohorts of 50 consecutive ICU patients requiring insulin infusions. INTERVENTION: Patients in the control cohort received insulin infusions titrated according to target blood glucose ranges and sliding scales at the physician's discretion. Patients in the interventional cohort received an insulin infusion adjusted using a standardized protocol targeting a blood glucose of 4.5-6.1 mmol/l (81-110 mg/dl). MEASUREMENTS AND MAIN RESULTS: Efficiency was measured by comparing the time to reach, and the time spent within, the target range between cohorts. Safety was assessed by comparing the incidence of severe hypoglycemia, the frequency of rescue dextrose administration and the cumulative time that the infusion was held for hypoglycemia between cohorts. Patients in the interventional cohort reached their target more rapidly (11.3+/-7.9 vs 16.4+/-12.6 h; p=0.028) and maintained their blood glucose within the target range longer (11.5+/-3.7 vs 7.1+/-5.0 h/day; p<0.001) than controls. The standardized protocol yielded a four-fold reduction in the incidence of severe hypoglycemia (4 vs 16%; p=0.046) and reduced the median frequency of dextrose rescue therapy (0 [0-0.91] vs 0.17 [0-1.2] episodes/patient per day; p=0.01) as compared to controls. CONCLUSION: Standardization of intensive insulin therapy improves the efficiency and safety of glycemic control in critically ill adults.
Notes: 0342-4642
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15127193
Author Address: Department of Pharmacy, Ottawa Hospital, General Campus, 501 Smyth, Ottawa, Ontario K1H 8L6, Canada. skanji@ottawahospital.on.ca

Reference Type: Journal Article
Record Number: 10
Author: Marik, P. E.; Raghavan, M.
Year: 2004
Title: Stress-hyperglycemia, insulin and immunomodulation in sepsis
Journal: Intensive Care Med
Volume: 30
Issue: 5
Pages: 748-56
Date: May
Accession Number: 14991101
Abstract: Stress-hyperglycemia and insulin resistance are exceedingly common in critically ill patients, particularly those with sepsis. Multiple pathogenetic mechanisms are responsible for this metabolic syndrome; however, increased release of pro-inflammatory mediators and counter-regulatory hormones may play a pivotal role. Recent data suggests that hyperglycemia may potentiate the pro-inflammatory response while insulin has the opposite effect. Furthermore, emerging evidence suggests that tight glycemic control will improve the outcome of critically ill patients. This paper reviews the pathophysiology of stress hyperglycemia in the critically ill septic patient and outlines a treatment strategy for the management of this disorder.
Notes: 0342-4642
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14991101
Author Address: Department of Critical Care Medicine, University of Pittsburgh Medical Center, 640A Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA. maripe@ccm.upmc.edu

Reference Type: Journal Article
Record Number: 8
Author: McMullin, J.; Brozek, J.; Jaeschke, R.; Hamielec, C.; Dhingra, V.; Rocker, G.; Freitag, A.; Gibson, J.; Cook, D.
Year: 2004
Title: Glycemic control in the ICU: a multicenter survey
Journal: Intensive Care Med
Volume: 30
Issue: 5
Pages: 798-803
Date: May
Accession Number: 15052384
Abstract: BACKGROUND: Intensive insulin therapy has recently been shown to decrease morbidity and mortality in the critically ill population in a large randomized clinical trial. OBJECTIVE: To determine the beliefs and attitudes of ICU clinicians about glycemic control. DESIGN: Self-administered survey. PARTICIPANTS: ICU nurses and physicians in five university-affiliated multidisciplinary ICUs. RESULTS: A total of 317 questionnaires were returned from 233 ICU nurses and 84 physicians. The reported clinically important threshold for hypoglycemia was 4 mmol/l (median, IQR 3-4 mmol/l). In non-diabetic patients, the clinically important threshold for hyperglycemia was 10 mmol/l (IQR 9-12 mmol/l); however, nurses had a significantly higher threshold than physicians (difference of 0.52 mmol/l (95% CI 0.09-0.94 mmol/l, P=0.018). In diabetic patients, the clinically important threshold for hyperglycemia was also 10 mmol/l (IQR 10-12 mmol/l), and again nurses had a significantly higher threshold than physicians (0.81 mmol/l, 95% CI 0.29-1.32 mmol/l, P=0.0023). Avoidance of hyperglycemia was judged most important for diabetic patients (87.7%, 95% CI 84.1-91.3%), patients with acute brain injury (84.5%, 95% CI 80.5-88.5%), patients with a recent seizure (74.4%, 95% CI 69.6-79.3%), patients with advanced liver disease (64.0%, 95% CI 58.7-69.3%), and for patients with acute myocardial infarction (64.0%, 95% CI 58.7-69.3%). Physicians expressed more concern than nurses about avoiding hyperglycemia in patients with acute myocardial infarction ( P=0.0004). ICU clinicians raised concerns about the accuracy of glucometer measurements in critically ill patients (46.1%, 95% CI 40.5-51.6%). CONCLUSIONS: Attention to these beliefs and attitudes could enhance the success of future clinical, educational and research efforts to modify clinician behavior and achieve better glycemic control in the ICU setting.
Notes: 0342-4642
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15052384
Author Address: Department of Medicine, McMaster University Medical Center, 1200 Main Street West, Hamilton, Ontario, Canada.

Reference Type: Journal Article
Record Number: 67
Author: Hansen, T. K.; Thiel, S.; Wouters, P. J.; Christiansen, J. S.; Van den Berghe, G.
Year: 2003
Title: Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels
Journal: J Clin Endocrinol Metab
Volume: 88
Issue: 3
Pages: 1082-8
Date: Mar
Accession Number: 12629088
Keywords: Anti-Inflammatory Agents/*therapeutic use
C-Reactive Protein/analysis
Critical Illness
Human
Insulin/*therapeutic use
Intensive Care Units
Mannose-Binding Lectin/*blood/deficiency
Prospective Studies
Support, Non-U.S. Gov't
Abstract: Adverse outcome of critical illness is often caused by systemic inflammation and sepsis. A recent study showed that mortality is significantly reduced by maintenance of normoglycemia using intensive insulin therapy. We examined whether the beneficial effects of intensive insulin therapy involve modulations of mannose-binding lectin (MBL) and C-reactive protein (CRP) levels. From a study of 1548 patients randomly assigned to either conventional treatment or intensive insulin therapy at an intensive care unit (ICU) we included all 451 patients who needed prolonged intensive care (>5 d). CRP and MBL concentrations were measured on admission, d 5, d 15, and the last day in the ICU. In all patients, serum MBL concentrations increased with time in the ICU (P < 0.0001). This acute phase response was suppressed by intensive insulin therapy at all time points studied (P < 0.02). Selectively in patients receiving conventional therapy, MBL concentrations at baseline were almost 3 times higher in survivors than in nonsurvivors (P = 0.04). Baseline CRP concentrations were elevated, but decreased with time in ICU (P < 0.0001). The decrease in CRP was significantly more pronounced in the intensive insulin-treated patients compared with the conventionally treated patients (P </= 0.02) at all time points. Multivariate logistic regression analysis, corrected for all other determinants of outcome, revealed that the antiinflammatory action on CRP, but not on MBL, largely explained the beneficial effects of intensive insulin therapy on morbidity and mortality. In conclusion, intensive insulin therapy exerts a powerful antiinflammatory effect during critical illness which at least partially explains improvement in morbidity and mortality. Possible adverse effects of low baseline MBL are overcome by intensive insulin therapy.
Notes: 0021-972x
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12629088
Author Address: Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark.

Reference Type: Journal Article
Record Number: 3
Author: Mesotten, D.; Wouters, P. J.; Peeters, R. P.; Hardman, K. V.; Holly, J. M.; Baxter, R. C.; Van den Berghe, G.
Year: 2004
Title: Regulation of the somatotropic axis by intensive insulin therapy during protracted critical illness
Journal: J Clin Endocrinol Metab
Volume: 89
Issue: 7
Pages: 3105-13
Date: Jul
Accession Number: 15240578
Keywords: Aged
Blood Glucose/drug effects/metabolism
Carrier Proteins/antagonists & inhibitors/blood
Chronic Disease
Critical Illness/*therapy
Female
Gene Expression/drug effects
Glycoproteins/antagonists & inhibitors
Growth Hormone/*metabolism
Human
Human Growth Hormone/secretion
Insulin/*therapeutic use
Insulin-Like Growth Factor Binding Protein 3/antagonists &
inhibitors/metabolism
Insulin-Like Growth Factor I/antagonists & inhibitors/genetics/metabolism
*Intensive Care
Intensive Care Units
Length of Stay
Liver/metabolism
Male
Middle Aged
Peptide Hydrolases/metabolism
RNA, Messenger/metabolism
Receptors, Somatotropin/genetics
Support, Non-U.S. Gov't
Survival Analysis
Abstract: The catabolic state of critical illness has been linked to the suppressed somatotropic GH-IGF-binding protein (IGFBP) axis. In critically ill patients it has been demonstrated that, compared with the conventional approach, which only recommended insulin therapy when blood glucose levels exceeded 12 mmol/liter, strict maintenance of blood glucose levels below 6.1 mmol/liter with intensive insulin therapy almost halved intensive care mortality, acute renal failure, critical illness polyneuropathy, and bloodstream infections. Poor blood glucose control in diabetes mellitus has also been associated with low serum IGF-I levels, which can be increased by insulin therapy. We hypothesized that intensive insulin therapy would improve the IGF-I axis, possibly contributing to the clinical correlates of anabolism. Therefore, this study of 363 patients, requiring intensive care for more than 7 d and randomly assigned to either conventional or intensive insulin therapy, examines the effects of intensive insulin therapy on the somatotropic axis. Contrary to expectation, intensive insulin therapy suppressed serum IGF-I, IGFBP-3, and acid-labile subunit concentrations. This effect was independent of survival of the critically ill patient. Concomitantly, serum GH levels were increased by intensive insulin therapy. The suppression of IGF-I in association with the increased GH levels suggests GH resistance induced by intensive insulin therapy, which was reflected by the decreased serum GH-binding protein levels. Intensive insulin therapy did not affect IGFBP-3 proteolysis, which was markedly higher in protracted critically ill patients compared with healthy controls. Also, intensive insulin therapy did not suppress the urea/creatinine ratio, a clinical correlate of catabolism. In conclusion, our data suggest that intensive insulin therapy surprisingly suppressed the somatotropic axis despite its beneficial effects on patient outcome. GH resistance accompanied this suppression of the IGF-I axis. To what extent and through which mechanisms the changes in the GH-IGF-IGFBP axis contributed to the survival benefit under intensive insulin therapy remain elusive.
Notes: 0021-972x
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15240578
Author Address: Department of Intensive Care Medicine, University Hospital Gasthuisberg, B-3000 Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.be

Reference Type: Journal Article
Record Number: 68
Author: Mesotten, D.; Swinnen, J. V.; Vanderhoydonc, F.; Wouters, P. J.; Van den Berghe, G.
Year: 2004
Title: Contribution of circulating lipids to the improved outcome of critical illness by glycemic control with intensive insulin therapy
Journal: J Clin Endocrinol Metab
Volume: 89
Issue: 1
Pages: 219-26
Date: Jan
Accession Number: 14715853
Keywords: Apache
Bacteremia/prevention & control
Blood Glucose/*analysis
CCAAT-Enhancer-Binding Proteins/genetics
Cholesterol/blood
*Critical Illness
DNA-Binding Proteins/genetics
Glucokinase/genetics
Hexokinase/genetics
Homeostasis
Insulin/*administration & dosage
Kidney Failure, Acute/prevention & control
Lipids/*blood
Lipoprotein Lipase/genetics
Lipoproteins, HDL/blood
Lipoproteins, HDL Cholesterol/blood
Lipoproteins, LDL/blood
Lipoproteins, LDL Cholesterol/blood
Liver/enzymology
Logistic Models
Monosaccharide Transport Proteins/genetics
Muscle, Skeletal/chemistry
Polyneuropathies/prevention & control
RNA, Messenger/analysis
Support, Non-U.S. Gov't
*Treatment Outcome
Triglycerides/blood
Abstract: Compared with the conventional approach, which recommended only insulin therapy when blood glucose levels exceeded 12 mmol/liter, strict maintenance of blood glucose levels less than 6.1 mmol/liter with intensive insulin therapy has shown to reduce intensive care mortality, acute renal failure, critical illness polyneuropathy, and bloodstream infections in critically ill patients by about 40%. This study of 363 patients, requiring intensive care for more than 7 d and randomly assigned to either conventional or intensive insulin therapy, examines the effects of intensive insulin therapy on glucose and lipid homeostasis and their respective impact on the improved outcome. Intensive insulin therapy effectively normalized blood glucose levels within 24 h, both in survivors and nonsurvivors. Intensive insulin therapy also increased serum levels of low-density lipoprotein (P = 0.007) and high-density lipoprotein (P = 0.005), whereas it suppressed the elevated serum triglyceride concentrations (P < 0.0001). Multivariate logistic regression analysis, corrected for baseline univariate risk factors and the effect on inflammation, indicated that lipid rather than glucose control independently determined the beneficial effects of intensive insulin therapy on morbidity and mortality. In postmortem biopsies obtained from 74 patients who died in the intensive care unit, intensive insulin therapy increased mRNA levels of skeletal muscle glucose transporter 4 (P = 0.02) and hexokinase (P = 0.03), unlike those of hepatic glucokinase. In conclusion, our data suggest that intensive insulin therapy normalizes blood glucose levels through stimulation of peripheral glucose uptake and concomitantly partially restores the abnormalities in the serum lipid profile, which may have contributed significantly to the improved outcome of protracted critical illness.
Notes: 0021-972x
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14715853
Author Address: Department of Intensive Care Medicine, University Hospital Gasthuisberg, Catholic University Leuven, B-3000 Leuven, Belgium.

Reference Type: Journal Article
Record Number: 37
Author: Tritos, N. A.; Mantzoros, C. S.
Year: 1998
Title: Clinical review 97: Syndromes of severe insulin resistance
Journal: J Clin Endocrinol Metab
Volume: 83
Issue: 9
Pages: 3025-30
Date: Sep
Accession Number: 9745395
Keywords: Glucose Tolerance Test
Human
*Insulin Resistance
Mutation
Phenotype
Receptor, Insulin/genetics
Syndrome
Therapeutics
Notes: 0021-972x
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9745395
Author Address: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Reference Type: Journal Article
Record Number: 63
Author: Umpierrez, G. E.; Isaacs, S. D.; Bazargan, N.; You, X.; Thaler, L. M.; Kitabchi, A. E.
Year: 2002
Title: Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes
Journal: J Clin Endocrinol Metab
Volume: 87
Issue: 3
Pages: 978-82
Date: Mar
Accession Number: 11889147
Keywords: Blood Glucose/analysis
Diabetes Mellitus/*blood/diagnosis/epidemiology/therapy
Fasting/blood
Female
*Hospitalization
Hospitals
Human
Hyperglycemia/diagnosis/epidemiology/*etiology/*mortality
Intensive Care
Length of Stay
Male
Medical Records
Middle Aged
Prognosis
United States
Abstract: Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 12% had no history of diabetes before the admission. Newly discovered hyperglycemia was associated with higher in-hospital mortality rate (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%; both P < 0.01). In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.
Notes: 0021-972x
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11889147
Author Address: Division of Endocrinology and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. gumpierrez@utmem.edu

Reference Type: Journal Article
Record Number: 38
Author: Virkamaki, A.; Ueki, K.; Kahn, C. R.
Year: 1999
Title: Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
Journal: J Clin Invest
Volume: 103
Issue: 7
Pages: 931-43
Date: Apr
Accession Number: 10194465
Keywords: 1-Phosphatidylinositol 3-Kinase/metabolism
Animals
Gene Targeting
Human
Insulin/*metabolism
*Insulin Resistance
Phosphorylation
Protein Binding
Receptor, Insulin/metabolism
*Signal Transduction
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
src Homology Domains
Notes: 0021-9738
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10194465
Author Address: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Reference Type: Journal Article
Record Number: 64
Author: Nylen, E. S.; Muller, B.
Year: 2004
Title: Endocrine changes in critical illness
Journal: J Intensive Care Med
Volume: 19
Issue: 2
Pages: 67-82
Date: Mar-Apr
Accession Number: 15070518
Keywords: *Adrenal Gland Hypofunction/diagnosis/etiology/therapy
Causality
Critical Care/methods
*Critical Illness
*Endocrine Diseases/diagnosis/etiology/therapy
*Growth Hormone/*deficiency/physiology/therapeutic use
Homeostasis
Human
Hydrocortisone/physiology/therapeutic use
*Hyperglycemia/diagnosis/etiology/therapy
Hypothalamo-Hypophyseal System/physiology/physiopathology
Pituitary-Adrenal System/physiology/physiopathology
Risk Factors
*Thyroid Diseases/diagnosis/etiology/therapy
Thyroid Function Tests
Treatment Outcome
Abstract: The homeostatic corrections that have emerged in the course of human evolution to cope with catastrophic events involve a complex multisystem endeavor, of which the endocrine contribution is an integral component. Although the repertoire of endocrine changes has been probed in some detail, discerning the vulnerabilities and failure of this system is far more challenging. The ensuing endocrine topics illustrate some of the current issues reflecting attempts to gain an improved insight and clinical outcome for critical illness.
Notes: 0885-0666
Journal Article
Review
Review, Academic
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15070518
Author Address: Department of Medicine, Section of Endocrinology, George Washington University School of Medicine, and Veterans Affairs Medical Center, 50 Irving St, NW, Rm GE246, Washington, DC 20422, USA. nylen4@aol.com

Reference Type: Journal Article
Record Number: 61
Author: Andersen, S. K.; Gjedsted, J.; Christiansen, C.; Tonnesen, E.
Year: 2004
Title: The roles of insulin and hyperglycemia in sepsis pathogenesis
Journal: J Leukoc Biol
Volume: 75
Issue: 3
Pages: 413-21
Date: Mar
Accession Number: 14657207
Keywords: Endocrine System
Human
Hyperglycemia/*complications
Immunity, Cellular
Insulin/*physiology
Sepsis/*etiology/immunology/metabolism
Abstract: Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group. Whether this is true for a population of sepsis patients, as such, has not been investigated in clinical trials, but evidence from in vitro studies and experimental sepsis suggests that this may be the case. The endocrinology of septic patients is characterized by a shift in the balance between insulin and its counter-regulatory hormones favoring the latter. This leads to prominent metabolic derangements composed of high release and low use of glucose, amino acids, and free fatty acids (FFA), resulting in increased blood levels of these substrates. Circulating, proinflammatory mediators further enhance this state of global catabolism. Increased levels of glucose and FFA have distinct effects on inflammatory signaling leading to additional release of proinflammatory mediators and endothelial and neutrophil dysfunction. Insulin has the inherent capability to counteract the metabolic changes observed in septic patients. Concomitantly, insulin therapy may act as a modulator of inflammatory pathways inhibiting the unspecific, inflammatory activation caused by metabolic substrates. Given these properties, insulin could conceivably be serving a dual purpose for the benefit of septic patients.
Notes: 0741-5400
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14657207
Author Address: Department of Anesthesiology and Intensive Care, Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark. ska@akhphd.au.dk

Reference Type: Journal Article
Record Number: 11
Author: Finney, S. J.; Zekveld, C.; Elia, A.; Evans, T. W.
Year: 2003
Title: Glucose control and mortality in critically ill patients
Journal: Jama
Volume: 290
Issue: 15
Pages: 2041-7
Date: Oct 15
Accession Number: 14559958
Keywords: Apache
Aged
Blood Glucose/*metabolism
Critical Illness/*mortality/therapy
Female
Hospital Mortality
Human
Hyperglycemia/drug therapy/*physiopathology
Insulin/*administration & dosage/therapeutic use
Intensive Care Units
Length of Stay
Male
Middle Aged
Outcome Assessment (Health Care)
Prospective Studies
Risk
Support, Non-U.S. Gov't
Abstract: CONTEXT: Hyperglycemia is common in critically ill patients, even in those without diabetes mellitus. Aggressive glycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear. OBJECTIVE: To determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients. DESIGN, SETTING, AND PATIENTS: Single-center, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral center for cardiorespiratory surgery and medicine. MAIN OUTCOME MEASURES: The primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death. RESULTS: Of 531 patients admitted to the ICU, 523 underwent analysis of their glycemic control. Twenty-four-hour control of blood glucose levels was variable. Rates of ICU and hospital mortality were 5.2% and 5.7%, respectively; median lengths of stay were 1.8 (interquartile range, 0.9-3.7) days and 6 (interquartile range, 4.5-8.3) days, respectively. Multivariable logistic regression demonstrated that increased administration of insulin was positively and significantly associated with ICU mortality (odds ratio, 1.02 [95% confidence interval, 1.01-1.04] at a prevailing glucose level of 111-144 mg/dL [6.1-8.0 mmol/L] for a 1-IU/d increase), suggesting that mortality benefits are attributable to glycemic control rather than increased administration of insulin. Also, the regression models suggest that a mortality benefit accrues below a predicted threshold glucose level of 144 to 200 mg/dL (8.0-11.1 mmol/L), with a speculative upper limit of 145 mg/dL (8.0 mmol/L) for the target blood glucose level. CONCLUSIONS: Increased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appear to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.
Notes: 1538-3598
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14559958
Author Address: Adult Intensive Care Unit, Royal Brompton Hospital, London, England.

Reference Type: Journal Article
Record Number: 36
Author: Montori, V. M.; Bistrian, B. R.; McMahon, M. M.
Year: 2002
Title: Hyperglycemia in acutely ill patients
Journal: Jama
Volume: 288
Issue: 17
Pages: 2167-9
Date: Nov 6
Accession Number: 12413377
Keywords: *Acute Disease
Hospitalization
Human
*Hyperglycemia/complications/etiology/physiopathology/prevention & control
Hypoglycemia
Notes: 0098-7484
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12413377
Author Address: Division of Endocrinology, Metabolism and Internal Medicine, Mayo Clinic, 200 First St SW, W18, Rochester, MN 55905, USA.

Reference Type: Journal Article
Record Number: 62
Author: Van den Berghe, G.; Bouillon, R.
Year: 2004
Title: Optimal control of glycemia among critically ill patients
Journal: Jama
Volume: 291
Issue: 10
Pages: 1198-9
Date: Mar 10
Accession Number: 15010439
Keywords: Blood Glucose/*metabolism
Critical Illness/*mortality
Human
Hyperglycemia/drug therapy/*physiopathology
Insulin/*administration & dosage
Notes: 1538-3598
Comment
Letter
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15010439

Reference Type: Journal Article
Record Number: 69
Author: Capes, S. E.; Hunt, D.; Malmberg, K.; Gerstein, H. C.
Year: 2000
Title: Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview
Journal: Lancet
Volume: 355
Issue: 9206
Pages: 773-8
Date: Mar 4
Accession Number: 10711923
Keywords: Blood Glucose/metabolism
Diabetes Mellitus/blood/*mortality
Heart Failure, Congestive/blood/mortality
Hospital Mortality
Human
Hyperglycemia/blood/*complications/mortality
Myocardial Infarction/blood/*mortality
Risk
Stress/blood/*complications
Abstract: BACKGROUND: High blood glucose concentration may increase risk of death and poor outcome after acute myocardial infarction. We did a systematic review and meta-analysis to assess the risk of in-hospital mortality or congestive heart failure after myocardial infarction in patients with and without diabetes who had stress hyperglycaemia on admission. METHODS: We did two searches of MEDLINE for English-language articles published from 1966 to October, 1998, a computerised search of Science Citation Index from 1980 to September, 1998, and manual searches of bibliographies. Two searchers identified all cohort studies or clinical trials reporting in-hospital mortality or rates of congestive heart failure after myocardial infarction in relation to glucose concentration on admission. We compared the relative risks of in-hospital mortality and congestive heart failure in hyperglycaemic and normoglycaemic patients with and without diabetes. FINDINGS: 14 articles describing 15 studies were identified. Patients without diabetes who had glucose concentrations more than or equal to range 6.1-8.0 mmol/L had a 3.9-fold (95% CI 2.9-5.4) higher risk of death than patients without diabetes who had lower glucose concentrations. Glucose concentrations higher than values in the range of 8.0-10.0 mmol/L on admission were associated with increased risk of congestive heart failure or cardiogenic shock in patients without diabetes. In patients with diabetes who had glucose concentrations more than or equal to range 10.0-11.0 mmol/L the risk of death was moderately increased (relative risk 1.7 [1.2-2.4]). INTERPRETATION: Stress hyperglycaemia with myocardial infarction is associated with an increased risk of in-hospital mortality in patients with and without diabetes; the risk of congestive heart failure or cardiogenic shock is also increased in patients without diabetes.
Notes: 0140-6736
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10711923
Author Address: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. scapes@fhs.csu.mcmaster.ca

Reference Type: Book Section
Record Number: 74
Author: Voigt, K.
Year: 2003
Title: Die Insulinsekretion wird durch Glucose stimuliert
Book Title: Lehrbuch der Physiologie, Herausgeber: S. Silbernagl, R. Klinke
City: Stuttgart
Publisher: Thieme Verlag
Pages: 486-488
Edition: 4

Reference Type: Journal Article
Record Number: 1
Author: Krinsley, J. S.
Year: 2004
Title: Effect of an intensive glucose management protocol on the mortality of critically ill adult patients
Journal: Mayo Clin Proc
Volume: 79
Issue: 8
Pages: 992-1000
Date: Aug
Accession Number: 15301325
Abstract: OBJECTIVE: To assess the effect of an intensive glucose management protocol in a heterogeneous population of critically ill adult patients. PATIENTS AND METHODS: This study consisted of 800 consecutive patients admitted after institution of the protocol (treatment group, between February 1, 2003, and January 10, 2004) and 800 patients admitted immediately preceding institution of the protocol (baseline group, between February 23, 2002, and January 31, 2003). The setting was a 14-bed medical-surgical intensive care unit (ICU) in a university-affiliated community teaching hospital. The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Continuous intravenous insulin was used if glucose values exceeded 200 mg/dL on 2 successive occasions. RESULTS: The 2 groups of patients were well matched, with similar age, sex, race, prevalence of diabetes mellitus, Acute Physiology and Chronic Health Evaluation II scores, and distribution of diagnoses. After institution of the protocol, the mean glucose value decreased from 152.3 to 130.7 mg/dL (P<.001), marked by a 56.3% reduction in the percentage of glucose values of 200 mg/dL or higher, without a significant change in hypoglycemia. The development of new renal insufficiency decreased 75% (P=-.03), and the number of patients undergoing transfusion of packed red blood cells decreased 18.7% (P=.04). Hospital mortality decreased 29.3% (P=.002), and length of stay in the ICU decreased 10.8% (P=.01). CONCLUSION: The protocol resulted in significantly improved glycemic control and was associated with decreased mortality, organ dysfunction, and length of stay in the ICU in a heterogeneous population of critically ill adult patients. These results support the adoption of this low-cost intervention as a standard of care for critically ill patients.
Notes: 0025-6196
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15301325
Author Address: Critical Care Unit, The Stamford Hospital, Stamford, Conn 06902, USA. Jkrinsley@stamhealth.org

Reference Type: Journal Article
Record Number: 66
Author: Van den Berghe, G.
Year: 2004
Title: Tight blood glucose control with insulin in "real-life" intensive care
Journal: Mayo Clin Proc
Volume: 79
Issue: 8
Pages: 977-8
Date: Aug
Accession Number: 15301322
Keywords: *Blood Glucose/analysis/drug effects
Critical Illness/mortality/*therapy
Drug Monitoring/methods/standards
Evidence-Based Medicine
Guideline Adherence/standards
Hospital Mortality
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
*Intensive Care/methods/standards
Practice Guidelines
Support, Non-U.S. Gov't
Notes: 0025-6196
Comment
Editorial
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15301322

Reference Type: Journal Article
Record Number: 39
Author: Heise, T.; Heinemann, L.; Starke, A. A.
Year: 1998
Title: Simulated postaggression metabolism in healthy subjects: metabolic changes and insulin resistance
Journal: Metabolism
Volume: 47
Issue: 10
Pages: 1263-8
Date: Oct
Accession Number: 9781632
Keywords: Adult
Carbohydrates/*metabolism
Fatty Acids, Nonesterified/blood
Human
*Insulin Resistance
Lactic Acid/metabolism
Male
Pyruvic Acid/metabolism
Stress/*metabolism
Abstract: Postaggression metabolism (PAM) is difficult to study in critically ill patients. The objective of this study was to simulate PAM in healthy subjects to quantify insulin sensitivity under these conditions. Six healthy men (age, 24 +/- 1 years; body mass index, 22.0 +/- 0.7 kg/m2 [mean +/- SE]) received an intravenous (i.v.) infusion of insulin-counteracting hormones (epinephrine 100 ng/kg/min, glucagon 16 ng/kg/min, hydrocortisone 5 microg/kg/min, and growth hormone [GH]-releasing hormone 50 microg/h) for 4 hours in addition to glucose (270 mg/kg/h). Control experiments used glucose only. In additional experiments, insulin sensitivity was measured by a two-step hyperinsulinemic glucose clamp with and without concomitant hormone infusion (insulin infusion rate, 2.5 and 5.0 mU/kg/min for hormone infusion or 1.0 and 2.5 mU/kg/min for control experiments). Plasma stress hormones reached levels comparable to severe PAM (epinephrine, 1,085 +/- 89 pg/mL; glucagon, 1,100 +/- 114 pg/mL; cortisone, 1,004 +/- 32 ng/mL; and GH, 20.6 +/- 6.1 pg/mL) in the hormone infusion experiment. This resulted in hyperglycemia and hyperinsulinemia (steady-state blood glucose, 19.7 +/- 0.4 mmol/L; serum insulin, 352 +/-8 pmol/L) in comparison to the control experiments with glucose infusion only (maximal blood glucose 7.2 +/- 0.8 mmol/L; serum insulin, 110 +/- 16 pmol/L). The insulin sensitivity index (S(I)) was 88% +/- 6% lower during hormone infusion (0.6 +/- 0.4 mL/min/m2/microU/min) compared with the control experiments (4.5 +/- 1.3 mL/min/m2/microU/min). Infusion of insulin-counteracting hormones at high doses allows simulation of the changes in carbohydrate metabolism observed in PAM in healthy subjects. The observed profound decrease in insulin sensitivity explains the hyperglycemia observed in nondiabetic critically ill patients. With this experimental setup, standardized investigations of therapeutic interventions in PAM should be possible.
Notes: 0026-0495
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9781632
Author Address: Department of Metabolic Diseases and Nutrition, World Health Organization Collaborating Centre for Diabetes, Heinrich-Heine-University, Dusseldorf, Germany.

Reference Type: Journal Article
Record Number: 40
Author: Peraldi, P.; Spiegelman, B.
Year: 1998
Title: TNF-alpha and insulin resistance: summary and future prospects
Journal: Mol Cell Biochem
Volume: 182
Issue: 1-2
Pages: 169-75
Date: May
Accession Number: 9609126
Keywords: Animals
Human
Insulin Resistance/*physiology
Signal Transduction/physiology
Tumor Necrosis Factor/genetics/metabolism/*physiology
Abstract: While the causes of obesity remain elusive, the relationship between obesity and insulin resistance is a well-established fact [1]. Insulin resistance is defined as a smaller than normal response to a certain dose of insulin, and contributes to several pathological problems of obese patients such as hyperlipidemia, arteriosclerosis and hypertension. Several pieces of evidence indicate that the cytokine tumor necrosis factor a (TNF-alpha) is an important player in the state of insulin resistance observed during obesity. In this review we will try to summarize what is known about the function of TNF-alpha in insulin resistance during obesity and how TNF-alpha interferes with insulin signaling.
Notes: 0300-8177
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9609126
Author Address: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Reference Type: Journal Article
Record Number: 18
Author: Jeschke, M. G.; Einspanier, R.; Klein, D.; Jauch, K. W.
Year: 2002
Title: Insulin attenuates the systemic inflammatory response to thermal trauma
Journal: Mol Med
Volume: 8
Issue: 8
Pages: 443-50
Date: Aug
Accession Number: 12435855
Keywords: Animals
Blood Glucose/drug effects
Burns/*drug therapy/physiopathology
Cytokines/blood/drug effects
Dose-Response Relationship, Drug
Electrolytes/blood
Hypoglycemic Agents/*pharmacology/therapeutic use
Inflammation/drug therapy
Insulin/*pharmacology/therapeutic use
Liver/drug effects/metabolism
Male
Rats
Rats, Sprague-Dawley
Transcription Factors/biosynthesis/drug effects/genetics/metabolism
Abstract: BACKGROUND: Insulin has been recently shown to decrease mortality and prevent the incidence of multi-organ failure in critically ill patients. The molecular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin therapy on the systemic inflammatory response. In vivo we determined the effect of insulin therapy on the inflammatory cascade, which was induced by thermal injury. MATERIALS AND METHODS: Thermally injured rats (30% TBSA) were randomly divided into two groups to receive either saline (n= 28) or insulin (n= 28). Our outcome measures encompassed the effect of insulin on pro- inflammatory cytokines, anti-inflammatory cytokines, and hepatic signal transcription factor mRNA expression. RESULTS: Insulin significantly decreased dose dependently serum pro-inflammatory cytokines IL-1beta at 1, 5, and 7 days, IL-6 at 1 day, MIF at 5 and 7 days, and TNF at 1 and 2 days after injury when compared with controls (p<0.05). Insulin increased anti-inflammatory cytokines IL-2 and IL-4 at 5 and 7 days after trauma, and IL-10 at 2, 5 and 7 days after trauma when compared with controls (p< 0.05). Pro-inflammatory signal transcription factors STAT-5 and C/EBP-beta mRNA were significantly decreased 1 and 2 days posttrauma; insulin increased anti-inflammatory signal transcription factor mRNA expression of SOCS-3 and RANTES 7 days after the injury (p< 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro- inflammatory and increasing the anti-inflammatory cas-cade, thereby restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.
Notes: 1076-1551
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12435855
Author Address: Klinik und Poliklinik fur Chirurgie. Klinikum der Universitat Regensburg, Germany. Mcjeschke@hotmail.com

Reference Type: Journal Article
Record Number: 43
Year: 2000
Title: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network
Journal: N Engl J Med
Volume: 342
Issue: 18
Pages: 1301-8
Date: May 4
Accession Number: 10793162
Keywords: Barotrauma/etiology/prevention & control
Comparative Study
Female
Human
Lung/injuries
Male
Middle Aged
Positive-Pressure Respiration
Respiration, Artificial/adverse effects/*methods
Respiratory Distress Syndrome, Adult/mortality/physiopathology/*therapy
Support, U.S. Gov't, P.H.S.
Survival Analysis
*Tidal Volume
Abstract: BACKGROUND: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. METHODS: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. RESULTS: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively. CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
Notes: 0028-4793
Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10793162

Reference Type: Journal Article
Record Number: 41
Author: Cline, G. W.; Petersen, K. F.; Krssak, M.; Shen, J.; Hundal, R. S.; Trajanoski, Z.; Inzucchi, S.; Dresner, A.; Rothman, D. L.; Shulman, G. I.
Year: 1999
Title: Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes
Journal: N Engl J Med
Volume: 341
Issue: 4
Pages: 240-6
Date: Jul 22
Accession Number: 10413736
Keywords: Adult
Aged
Biological Transport
Blood Glucose/metabolism
Diabetes Mellitus, Type II/*metabolism
Extracellular Space/metabolism
Female
Glucose/*metabolism
Glucose-6-Phosphate/metabolism
Glycogen/biosynthesis/*metabolism
Hexokinase/metabolism
Human
Hyperglycemia/metabolism
Hyperinsulinism/metabolism
Insulin/*metabolism/physiology
Magnetic Resonance Spectroscopy
Male
Middle Aged
Models, Biological
Muscle, Skeletal/*metabolism
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Abstract: BACKGROUND: Insulin resistance, a major factor in the pathogenesis of type 2 diabetes mellitus, is due mostly to decreased stimulation of glycogen synthesis in muscle by insulin. The primary rate-controlling step responsible for the decrease in muscle glycogen synthesis is not known, although hexokinase activity and glucose transport have been implicated. METHODS: We used a novel nuclear magnetic resonance approach with carbon-13 and phosphorus-31 to measure intramuscular glucose, glucose-6-phosphate, and glycogen concentrations under hyperglycemic conditions (plasma glucose concentration, approximately 180 mg per deciliter [10 mmol per liter]) and hyperinsulinemic conditions in six patients with type 2 diabetes and seven normal subjects. In vivo microdialysis of muscle tissue was used to determine the gradient between plasma and interstitial-fluid glucose concentrations, and open-flow microperfusion was used to determine the concentrations of insulin in interstitial fluid. RESULTS: The time course and concentration of insulin in interstitial fluid were similar in the patients with diabetes and the normal subjects. The rates of whole-body glucose metabolism and muscle glycogen synthesis and the glucose-6-phosphate concentrations in muscle were approximately 80 percent lower in the patients with diabetes than in the normal subjects under conditions of matched plasma insulin concentrations. The mean (+/-SD) intracellular glucose concentration was 2.0+/-8.2 mg per deciliter (0.11+/-0.46 mmol per liter) in the normal subjects. In the patients with diabetes, the intracellular glucose concentration was 4.3+/-4.9 mg per deciliter (0.24+/-0.27 mmol per liter), a value that was 1/25 of what it would be if hexokinase were the rate-controlling enzyme in glucose metabolism. CONCLUSIONS: Impaired insulin-stimulated glucose transport is responsible for the reduced rate of insulin-stimulated muscle glycogen synthesis in patients with type 2 diabetes mellitus.
Notes: 0028-4793
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10413736
Author Address: Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn. 06536-8012, USA.

Reference Type: Journal Article
Record Number: 21
Author: Evans, T. W.
Year: 2001
Title: Hemodynamic and metabolic therapy in critically ill patients
Journal: N Engl J Med
Volume: 345
Issue: 19
Pages: 1417-8
Date: Nov 8
Accession Number: 11794176
Keywords: Blood Glucose/drug effects
Critical Illness/therapy
Hemodynamic Processes
Hospital Mortality
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Intensive Care/methods
*Monitoring, Physiologic
Postoperative Care/*methods
Sepsis/physiopathology/*therapy
Notes: 0028-4793
Comment
Editorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11794176

Reference Type: Journal Article
Record Number: 77
Author: Hirsch, I. B.; Coviello, A.
Year: 2002
Title: Intensive insulin therapy in critically ill patients
Journal: N Engl J Med
Volume: 346
Issue: 20
Pages: 1586-8; author reply 1586-8
Date: May 16
Accession Number: 12015401
Keywords: Blood Glucose/*metabolism
Critical Illness/*therapy
Human
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Intensive Care Units
Macrophage Migration-Inhibitory Factors/*antagonists &
inhibitors/metabolism
*Postoperative Care
Tumor Necrosis Factor/*antagonists & inhibitors/metabolism
Notes: 1533-4406
Comment
Letter
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12015401

Reference Type: Journal Article
Record Number: 42
Author: Shepherd, P. R.; Kahn, B. B.
Year: 1999
Title: Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus
Journal: N Engl J Med
Volume: 341
Issue: 4
Pages: 248-57
Date: Jul 22
Accession Number: 10413738
Keywords: Adipocytes/metabolism
Animals
Biological Transport
Diabetes Mellitus/*metabolism
Glucose/*metabolism
Hemostasis
Human
Insulin/*metabolism/physiology
Insulin Resistance
Intracellular Membranes
Monosaccharide Transport Proteins/*metabolism
Muscle, Skeletal/metabolism
Signal Transduction
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Notes: 0028-4793
Comment
Journal Article
Review
Review, Academic
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10413738
Author Address: Department of Biochemistry and Molecular Biology, University College London.

Reference Type: Journal Article
Record Number: 22
Author: van den Berghe, G.; Wouters, P.; Weekers, F.; Verwaest, C.; Bruyninckx, F.; Schetz, M.; Vlasselaers, D.; Ferdinande, P.; Lauwers, P.; Bouillon, R.
Year: 2001
Title: Intensive insulin therapy in the critically ill patients
Journal: N Engl J Med
Volume: 345
Issue: 19
Pages: 1359-67
Date: Nov 8
Accession Number: 11794168
Keywords: Apache
Blood Glucose/drug effects/metabolism
Critical Illness/*therapy
Female
*Hospital Mortality
Human
Hypoglycemic Agents/administration & dosage/*therapeutic use
Insulin/administration & dosage/*therapeutic use
Intensive Care/methods
Intensive Care Units
Length of Stay
Logistic Models
Male
Middle Aged
Postoperative Care/*methods
Prospective Studies
Respiration, Artificial
Support, Non-U.S. Gov't
Survival Analysis
Abstract: BACKGROUND: Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. CONCLUSIONS: Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.
Notes: 0028-4793
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11794168
Author Address: Department of Intensive Care Medicine, Catholic University of Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.be

Reference Type: Generic
Record Number: 51
Author: Brady, M. J.; Saltiel, A. R.
Year: 1999
Title: Insulin and Glucagon
Secondary Title: Nature Encyclopedia of Life Sciences
Publisher: Nature Publishing Group
Volume: 2004
Number: 13.08.
URL: http://www.els.net

Reference Type: Generic
Record Number: 78
Author: Najjar, S.
Year: 2000
Title: Insulin action: molecular basis of Diabetes
Secondary Title: Nature Encyclopedia of Life Sciences
Publisher: Nature Publishing Group
Volume: 2004
Number: 13.09.
URL: http://www.els.net

Reference Type: Journal Article
Record Number: 45
Author: Lill, N.
Year: 2001
Title: Insulinformulierungen
Journal: Pharm Unserer Zeit
Volume: 30
Issue: 1
Pages: 56-62
Date: Jan
Accession Number: 11233184
Keywords: Chemistry, Pharmaceutical
Excipients
Human
Hypoglycemic Agents/*administration & dosage/chemistry/therapeutic use
Insulin/*administration & dosage/chemistry/therapeutic use
Notes: 0048-3664
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11233184
Author Address: Aventis Pharma Deutschland GmbH, Pharmaceutical Sciences, H770 65926 Frankfurt am Main. Norbert.Lill@aventis.com

Reference Type: Journal Article
Record Number: 46
Author: Zündorf, I.; Dingermann, T.
Year: 2001
Title: Vom Rinder-, Schweine-, Pferdeinsulin zum Humaninsulin: Die biotechnische und gentechnische Insulinherstellung
Journal: Pharm Unserer Zeit
Volume: 30
Issue: 1
Pages: 27-32
Date: Jan
Accession Number: 11233180
Keywords: Animals
*Biotechnology
Cattle
Comparative Study
*Genetic Engineering
Horses
Human
Insulin/biosynthesis/chemistry/genetics/*pharmacology
Recombinant Proteins/biosynthesis/genetics/pharmacology
Swine
Notes: 0048-3664
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11233180
Author Address: Institut fur Pharmazeutische Biologie, Johann Wolfgang Goethe-Universitat, Biozentrum, Marie-Curie-Str. 9, 60439 Frankfurt a.M. Zuendorf@em.uni-frankfurt.de

Reference Type: Journal Article
Record Number: 59
Author: Mizock, B. A.
Year: 2003
Title: Blood glucose management during critical illness
Journal: Rev Endocr Metab Disord
Volume: 4
Issue: 2
Pages: 187-94
Date: May
Accession Number: 12766547
Keywords: Acute Disease
Blood Glucose/*metabolism
Carbohydrates/metabolism
Critical Illness
Human
Hyperglycemia/diagnosis/etiology/*physiopathology/*therapy
Insulin/therapeutic use
Parenteral Nutrition, Total/adverse effects
Stress/*physiopathology
Notes: 1389-9155
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12766547
Author Address: Department of Medicine, Cook County Hospital, Chicago, IL, USA. bmizock@earthlink.net

Reference Type: Journal Article
Record Number: 47
Author: Bonville, D. A.; Parker, T. S.; Levine, D. M.; Gordon, B. R.; Hydo, L. J.; Eachempati, S. R.; Barie, P. S.
Year: 2004
Title: The relationships of hypocholesterolemia to cytokine concentrations and mortality in critically ill patients with systemic inflammatory response syndrome
Journal: Surg Infect (Larchmt)
Volume: 5
Issue: 1
Pages: 39-49
Date: Spring
Accession Number: 15142422
Keywords: Apache
Aged
Analysis of Variance
Biological Markers/analysis
Cholesterol/blood/*metabolism
Comparative Study
Critical Illness/*mortality
Cytokines/blood/*metabolism
Female
Human
Intensive Care Units
Logistic Models
Male
Middle Aged
Predictive Value of Tests
Probability
Prospective Studies
Risk Assessment
Sensitivity and Specificity
Sepsis Syndrome/*diagnosis/*mortality/therapy
Survival Analysis
Abstract: BACKGROUND: Decreased concentrations of total cholesterol, lipoproteins, and lipoprotein cholesterols occur early in the course of critical illness. Low cholesterol concentrations correlate with high concentrations of cytokines such as interleukin (IL)-6 and IL-10, and may be due to decreased synthesis or increased catabolism of cholesterol. Low cholesterol concentrations have been associated clinically with several adverse outcomes, including the development of nosocomial infections. The study was performed to test the hypothesis that a low cholesterol concentration predicts mortality and secondarily predicts the development of organ dysfunction in critical surgical illness. METHODS: A prospective study was undertaken of 215 patients admitted to a university surgical ICU with systemic inflammatory response syndrome (SIRS). Serial blood samples were collected within 24 h of admission, as well as on the morning of days 2, 4, and 7 of the ICU stay for as long as the patients were in the ICU. Demographic data and predetermined outcomes were noted. RESULTS: One hundred nine patients had at least two samples drawn and form the population for analysis. Sixty-two of the patients had three samples obtained, whereas 42 patients had four samples obtained. By univariate analysis, non-survivors were more severely ill on admission (APACHE III), more likely to have been admitted to the ICU as an emergency, more likely to develop a nosocomial infection, and more likely to develop severe organ dysfunction (MODS) (all, p < 0.05). Death was associated on day 1 with increased concentrations of sIL2R, IL-6, IL-10, and sTNFR-p75 (all, p < 0.01), but there were initially no differences in serum lipid concentrations. However, by day 2, concentrations of IL-6, IL-10, and cholesterol had decreased significantly (all, p < 0.05) from day 1 in non-survivors but not in survivors; the difference in serum cholesterol concentration persisted to day 7 (p < 0.05). Persistently elevated concentrations of IL-6 and IL-10 were observed in patients who developed severe MODS. By logistic regression, increased APACHE III score, development of a nosocomial infection, and decreased cholesterol concentration were independently associated with mortality. CONCLUSIONS: Decreased serum cholesterol concentration is an independent predictor of mortality in critically ill surgical patients. Repletion of serum lipids is a feasible therapeutic approach for the management of critical illness.
Notes: 1096-2964
Journal Article
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15142422
Author Address: Department of Surgery, Weill Medical College of Cornell University, New York, New York, USA.

Reference Type: Journal Article
Record Number: 57
Author: Plank, L. D.; Hill, G. L.
Year: 2000
Title: Sequential metabolic changes following induction of systemic inflammatory response in patients with severe sepsis or major blunt trauma
Journal: World J Surg
Volume: 24
Issue: 6
Pages: 630-8
Date: Jun
Accession Number: 10773114
Keywords: Adolescent
Adult
Body Composition
Critical Illness
Cytokines/blood
Energy Metabolism
Female
Human
Male
Middle Aged
Peritonitis/blood
Sepsis Syndrome/*metabolism
Wounds, Nonpenetrating/*metabolism
Abstract: We have recently completed studies in critically ill patients with severe sepsis or major trauma that investigated sequential changes in the metabolic response following admission to the intensive care unit. Protein, water, and energy metabolism were measured using in vivo neutron activation analysis, tracer dilution, dual-energy x-ray absorptiometry, and indirect calorimetry. Over the 3-week study period both groups of patients lost 13% of their total body protein. The severe sepsis patients retained twice the volume of fluid of those with major trauma, and the return to normal hydration in the sepsis group was correspondingly prolonged, especially for those in the elderly age group. In both groups of patients resting energy expenditure increased progressively over the first week to around 40% above normal and was still elevated 3 weeks from onset of illness. A twofold increase in total energy expenditure occurred in both groups of patients between the first and second weeks of critical care admission. The prolonged hypermetabolism throughout the study period was not reflected in the concentrations of circulating proinflammatory cytokines, which fell rapidly over the first week. The pattern of changes seen in plasma proinflammatory and antiinflammatory cytokine concentrations is similar for sepsis and trauma. The remarkably similar metabolic sequelae seen in critically ill patients following the onset of severe sepsis or major trauma may constitute a universal response to the induction of the systemic inflammatory response syndrome.
Notes: 0364-2313
Journal Article
Review
Review, Tutorial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10773114
Author Address: University Department of Surgery, Auckland Hospital, Fifth Floor, Private Bag 92-024, Auckland 1003, New Zealand.

Reference Type: Journal Article
Record Number: 48
Author: Jauch, K. W.; Kroner, G.; Hermann, A.; Inthorn, D.; Hartl, W.; Gunther, B.
Year: 1995
Title: Postoperative Infusionstherapie: Elektrolytlösung im Vergleich zu hypokalorischen Glukose- bzw. Zuckeraustausch-Aminosäurenlösungen
Journal: Zentralbl Chir
Volume: 120
Issue: 9
Pages: 682-8
Accession Number: 7483868
Keywords: Abdomen/surgery
Aged
Amino Acids/*administration & dosage/blood
Blood Glucose/metabolism
Blood Proteins/metabolism
Blood Urea Nitrogen
Comparative Study
Critical Care
Energy Intake/physiology
English Abstract
Female
Fluid Therapy/*methods
Glucose Solution, Hypertonic/*administration & dosage
Human
Insulin/blood
Male
Middle Aged
Nutritional Requirements
Parenteral Nutrition, Total/*methods
Postoperative Care/*methods
Sorbitol/*administration & dosage
Xylitol/*administration & dosage
Abstract: OBJECTIVES: Comparison of early postoperative hypocaloric nutrition with glucose or xylitol/sorbitol- amino acid solutions versus saline alone. Influence on substrate, especially protein metabolism. DESIGN: Prospective randomized study. SETTING: Intensive care unit of an university hospital. PATIENTS: 44 patients in three groups after major surgery with necessity of intensive care. RESULTS: Hypocaloric infusions were well tolerated immediately after operation and positively influenced functional proteins and N-balance. During saline infusion protein parameters deteriorated significantly already after 24 to 36 hours. Glucose was not inferior to the xylitol/sorbitol solution and both resulted in a stable metabolic state during four days. CONCLUSIONS: After major trauma or surgery hypocaloric nutrition should be started within 24 hours and can be given already directly after the operation period without metabolic deterioration.
Notes: 0044-409x
Clinical Trial
Journal Article
Randomized Controlled Trial
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7483868
Author Address: Chirurgische Klinik und Poliklinik, Ludwig-Maximilians-Universitat Munchen.