Intravenous GLP-1 (7-36) amide for prevention of hyperglycemia during cardiac surgery: a randomized, double-blind, placebo-controlled study.

OBJECTIVE The authors sought to evaluate the efficacy of an intravenous glucagon-like peptide-1 (GLP-1) infusion, compared with placebo, to mitigate intraoperative hyperglycemia. DESIGN Prospective, double-blinded, randomized, placebo-controlled. SETTING University hospital. PARTICIPANTS Diabetic (non-insulin dependent) and non-diabetic patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS Patients were randomized in a 1:1 fashion to GLP-1 (7-36) amide infusion (1.5 pmol/kg/min) or placebo. Insulin was administered intraoperatively to both groups per a standardized protocol. MEASUREMENTS AND MAIN RESULTS A total of 77 patients were included for analysis (GLP-1, n = 37; placebo, n = 40). Mean blood glucose during cardiopulmonary bypass was 127.5 mg/dL and 142.5 mg/dL (p = 0.002) in the GLP-1 and placebo groups, respectively. Mean blood glucose values during the entire intraoperative course were 12.2 mg/dL lower for subjects given GLP-1 (95% CI 2.3, 22, p = 0.015), independent of time. During the period of cardiopulmonary bypass, mean blood glucose values in subjects given GLP-1 were 14.1 mg/dL lower than those who received placebo (95% CI 3.5, 24.8, p = 0.009), independent of time. The incidence of hypoglycemia did not differ significantly between the 2 groups. CONCLUSIONS Administration of intravenous GLP-1 (7-36) amide to patients undergoing cardiac surgery significantly reduced their plasma glucose levels intraoperatively and may represent a novel therapeutic strategy to prevent perioperative hyperglycemia.

[1]  John A Myburgh,et al.  Hypoglycemia and risk of death in critically ill patients. , 2012, The New England journal of medicine.

[2]  S. Mudaliar,et al.  The incretin hormones: from scientific discovery to practical therapeutics , 2012, Diabetologia.

[3]  R. Carini,et al.  Effects of Preoperative Oral Carbohydrate Supplementation on Postoperative Metabolic Stress Response of Patients Undergoing Elective Abdominal Surgery , 2012, World Journal of Surgery.

[4]  N. Pinelli,et al.  Exogenous Glucagon-Like Peptide-1 for Hyperglycemia in Critically Ill Patients , 2012, The Annals of pharmacotherapy.

[5]  J. Prins,et al.  Update on incretin hormones , 2011, Annals of the New York Academy of Sciences.

[6]  C. Mélot,et al.  Mild hypoglycemia is strongly associated with increased intensive care unit length of stay , 2011, Annals of intensive care.

[7]  D. Yabe,et al.  Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and β cell preservation. , 2011, Progress in biophysics and molecular biology.

[8]  C. Mélot,et al.  Mild hypoglycemia is independently associated with increased mortality in the critically ill , 2011, Critical care.

[9]  J. Carew,et al.  Hypoglycemia with intensive insulin therapy after cardiac surgery: predisposing factors and association with mortality. , 2011, The Journal of thoracic and cardiovascular surgery.

[10]  Y. Seino.  Understanding the incretin effect. , 2011, The Journal of clinical endocrinology and metabolism.

[11]  S. Schwartz,et al.  Glycemic control and weight reduction without causing hypoglycemia: the case for continued safe aggressive care of patients with type 2 diabetes mellitus and avoidance of therapeutic inertia. , 2010, Mayo Clinic proceedings.

[12]  Benjamin Glaser,et al.  Effects of moderate intensity glycemic control after cardiac surgery. , 2010, The Annals of thoracic surgery.

[13]  S. Schwartz,et al.  Type 2 diabetes mellitus and the cardiometabolic syndrome: impact of incretin-based therapies , 2010, Diabetes, metabolic syndrome and obesity : targets and therapy.

[14]  M. Nauck,et al.  Is the Diminished Incretin Effect in Type 2 Diabetes Just an Epi-Phenomenon of Impaired β-Cell Function? , 2010, Diabetes.

[15]  Michael A. Via,et al.  Impaired postoperative hyperglycemic stress response associated with increased mortality in patients in the cardiothoracic surgery intensive care unit. , 2010, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[16]  Q. Wang,et al.  Randomized clinical trial to compare the effects of preoperative oral carbohydrate versus placebo on insulin resistance after colorectal surgery , 2010, The British journal of surgery.

[17]  Johan Groeneveld,et al.  A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study , 2009, Intensive Care Medicine.

[18]  S. Barnett,et al.  Surgery for aortic and mitral valve disease in the United States: a trend of change in surgical practice between 1998 and 2005. , 2009, The Journal of thoracic and cardiovascular surgery.

[19]  Victor Novack,et al.  Continuous Perioperative Insulin Infusion Decreases Major Cardiovascular Events in Patients Undergoing Vascular Surgery: A Prospective, Randomized Trial , 2009, Anesthesiology.

[20]  D. B. Dock-Nascimento,et al.  Preoperative Fasting of 2 Hours Minimizes Insulin Resistance and Organic Response to Trauma After Video-Cholecystectomy: A Randomized, Controlled, Clinical Trial , 2009, World Journal of Surgery.

[21]  Stephane Heritier,et al.  Intensive versus conventional glucose control in critically ill patients. , 2009, The New England journal of medicine.

[22]  R. Shemin,et al.  The Society of Thoracic Surgeons practice guideline series: Blood glucose management during adult cardiac surgery. , 2009, The Annals of thoracic surgery.

[23]  R. Freeman,et al.  Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function , 2009, Diabetes.

[24]  B. Göke,et al.  Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions , 2008, Critical care.

[25]  L. Foubert,et al.  Tight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patients , 2008, Critical care.

[26]  Diane Marshall,et al.  Hyperglycemia predicts mortality after CABG: postoperative hyperglycemia predicts dramatic increases in mortality after coronary artery bypass graft surgery. , 2008, Journal of diabetes and its complications.

[27]  G. Angelini,et al.  Inadequate Blood Glucose Control Is Associated With In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery , 2008, Circulation.

[28]  H. Tymkew,et al.  A randomized study in diabetic patients undergoing cardiac surgery comparing computer-guided glucose management with a standard sliding scale protocol. , 2008, Journal of cardiothoracic and vascular anesthesia.

[29]  J. Holst.  The physiology of glucagon-like peptide 1. , 2007, Physiological reviews.

[30]  R. Shannon,et al.  Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. , 2007, The American journal of cardiology.

[31]  D. Drucker.  The biology of incretin hormones. , 2006, Cell metabolism.

[32]  Charles E. Smith,et al.  Intraoperative glucose control in diabetic and nondiabetic patients during cardiac surgery. , 2005, Journal of cardiothoracic and vascular anesthesia.

[33]  Howard Cabral,et al.  Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events , 2004, Circulation.

[34]  G. Grunkemeier,et al.  Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. , 2003, The Journal of thoracic and cardiovascular surgery.

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

[36]  J. Takala,et al.  Metabolic changes after cardiac surgery , 2001, Current opinion in clinical nutrition and metabolic care.

[37]  M. Chaney,et al.  Attempting to maintain normoglycemia during cardiopulmonary bypass with insulin may initiate postoperative hypoglycemia. , 1999, Anesthesia and analgesia.

[38]  O. Ljungqvist,et al.  Preoperative oral carbohydrates and postoperative insulin resistance. , 1999, Clinical nutrition.

[39]  O. Ljungqvist,et al.  Preoperative oral carbohydrate administration reduces postoperative insulin resistance. , 1998, Clinical nutrition.

[40]  K. Malmberg.  Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus , 1997, BMJ.

[41]  F. Kuntschen,et al.  Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia. , 1986, The Journal of thoracic and cardiovascular surgery.

[42]  Y. Kawashima,et al.  Carbohydrate and lipid metabolism in open-heart surgery. , 1977, The Journal of thoracic and cardiovascular surgery.

[43]  I. Mandelbaum,et al.  Effect of extracorporeal circulation upon insulin. , 1968, The Journal of thoracic and cardiovascular surgery.

[44]  Y. Tamura,et al.  Attempted suicide with liraglutide overdose did not induce hypoglycemia. , 2013, Diabetes research and clinical practice.

[45]  R. Hewitt,et al.  Plasma insulin response during cardiopulmonary bypass. , 1971, Surgical forum.