title: The glucoregulatory benefits of glucagon-like peptide-1 (7-36) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study.
abstract: OBJECTIVE
  Intensive insulin therapy for tight glycemic control in critically ill surgical patients has been shown to reduce mortality; however, intensive insulin therapy is associated with iatrogenic hypoglycemia and increased variability of blood glucose levels. The incretin glucagon-like peptide-1 (7-36) amide is both insulinotropic and insulinomimetic and has been suggested as an adjunct to improve glycemic control in critically ill patients. We hypothesized that the addition of continuous infusion of glucagon-like peptide-1 to intensive insulin therapy would result in better glucose control, reduced requirement of exogenous insulin administration, and fewer hypoglycemic events.
  
  
  METHODS
  Prospective, randomized, double-blind, placebo-controlled clinical trial.
  
  
  METHODS
  Surgical or burn ICU.
  
  
  METHODS
  Eighteen patients who required intensive insulin therapy.
  
  
  METHODS
  A 72-hour continuous infusion of either glucagon-like peptide-1 (1.5 pmol/kg/min) or normal saline plus intensive insulin therapy.
  
  
  RESULTS
  The glucagon-like peptide-1 cohort (n = 9) and saline cohort (n = 9) were similar in age, Acute Physiology and Chronic Health Evaluation score, and history of diabetes. Blood glucose levels in the glucagon-like peptide-1 group were better controlled with much less variability. The coefficient of variation of blood glucose ranged from 7.2% to 30.4% in the glucagon-like peptide-1 group and from 19.8% to 56.8% in saline group. The mean blood glucose coefficient of variation for the glucagon-like peptide-1 and saline groups was 18.0% ± 2.7% and 30.3% ± 4.0% (p = 0.010), respectively. The 72-hour average insulin infusion rates were 3.37 ± 0.61 and 4.57 ± 1.18 U/hr (p = not significant). The incidents of hypoglycemia (≤ 2.78 mmol/L) in both groups were low (one in the glucagon-like peptide-1 group, three in the saline group).
  
  
  CONCLUSIONS
  Glucagon-like peptide-1 (7-36) amide is a safe and efficacious form of adjunct therapy in patients with hyperglycemia in the surgical ICU setting. Improved stability of blood glucose is a favorable outcome, which enhances the safety of intensive insulin therapy. Larger studies of this potentially valuable therapy for glycemic control in the ICU are justified.
authors.affiliation: 1Department of Medicine, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD. 2Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD. 3Clinical Physiology Branch, National Institute on Aging, Baltimore, MD. 4Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors.forename: Panagis
authors.initials: P
authors.lastname: Galiatsatos
authors.forename: B Robert
authors.initials: BR
authors.lastname: Gibson
authors.forename: Atoosa
authors.initials: A
authors.lastname: Rabiee
authors.forename: Olga
authors.initials: O
authors.lastname: Carlson
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Richard P
authors.initials: RP
authors.lastname: Shannon
authors.forename: Dana K
authors.initials: DK
authors.lastname: Andersen
authors.forename: Dariush
authors.initials: D
authors.lastname: Elahi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D017052:Hospital Mortality; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010865:Pilot Projects; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D011446:Prospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D052216:Glucagon-Like Peptide 1