title: Study protocol of a randomised controlled trial comparing perioperative intravenous insulin, GIK or GLP-1 treatment in diabetes-PILGRIM trial.
abstract: BACKGROUND
  Diabetes mellitus (DM) is associated with poor outcome after surgery. The prevalence of DM in hospitalised patients is up to 40%, meaning that the anaesthesiologist will encounter a patient with DM in the operating room on a daily basis. Despite an abundance of published glucose lowering protocols and the known negative outcomes associated with perioperative hyperglycaemia in DM, there is no evidence regarding the optimal intraoperative glucose lowering treatment. In addition, protocol adherence is usually low and protocol targets are not simply met. Recently, incretins have been introduced to lower blood glucose. The main hormone of the incretin system is glucagon-like peptide-1 (GLP-1). GLP-1 increases insulin and decreases glucagon secretion in a glucose-dependent manner, resulting in glucose lowering action with a low incidence of hypoglycaemia. We set out to determine the optimal intraoperative treatment algorithm to lower glucose in patients with DM type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GPL-1 (liragludite, LG) treatment.
  
  
  METHODS
  This is a multicentre randomised open label trial in patients with DM type 2 undergoing non-cardiac surgery. Patients are randomly assigned to one of three study arms; intraoperative glucose-insulin-potassium infusion (GIK), intraoperative sliding-scale insulin boluses (BR) or GPL-1 pre-treatment with liraglutide (LG). Capillary glucose will be measured every hour. If necessary, in all study arms glucose will be adjusted with an intravenous bolus of insulin. Researchers, care givers and patients will not be blinded for the assigned treatment. The main outcome measure is the difference in median glucose between the three study arms at 1 hour postoperatively. We will include 315 patients, which gives us a 90% power to detect a 1 mmol l(-1) difference in glucose between the study arms.
  
  
  CONCLUSIONS
  The PILGRIM trial started in January 2014 and will provide relevant information on the perioperative use of GLP-1 agonists and the optimal intraoperative treatment algorithm in patients with diabetes mellitus type 2.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT02036372.
authors.affiliation: Department of Anaesthesiology, Academic Medical Centre, Amsterdam, the Netherlands, Postbus 22660, 1100 DD Amsterdam, the Netherlands.
authors.forename: Jorinde A W
authors.initials: JA
authors.lastname: Polderman
authors.affiliation: Department of Anaesthesiology, Diakonessenhuis, Utrecht, the Netherlands, Bosboomstraat 1, 3582 KE Utrecht, the Netherlands.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Houweling
authors.affiliation: Department of Anaesthesiology, Academic Medical Centre, Amsterdam, the Netherlands, Postbus 22660, 1100 DD Amsterdam, the Netherlands.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Department of Internal Medicine, Academic Medical Centre, Amsterdam, the Netherlands, Postbus 22660, 1100 DD Amsterdam, the Netherlands.
authors.forename: J Hans
authors.initials: JH
authors.lastname: DeVries
authors.affiliation: Department of Anaesthesiology, Academic Medical Centre, Amsterdam, the Netherlands, Postbus 22660, 1100 DD Amsterdam, the Netherlands.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.affiliation: Department of Anaesthesiology, Academic Medical Centre, Amsterdam, the Netherlands, Postbus 22660, 1100 DD Amsterdam, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hermanides
mesh_terms: D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D000069450:Liraglutide; D019990:Perioperative Care / Q000379:methods; D011183:Postoperative Complications / Q000517:prevention & control; D011188:Potassium / Q000008:administration & dosage / Q000627:therapeutic use; D012107:Research Design; D013514:Surgical Procedures, Operative / Q000379:methods
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D011188:Potassium
keywords: Diabetes mellitus type 2; GLP-1 agonist; Perioperative management