Perioperative Insulin, GIK or GLP-1 Treatment in Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
The incidence of diabetes mellitus type II is increasing. More and more patients who need surgery have diabetes mellitus type II. Despite an enormous amount of glucose lowering protocols and the proven negative effects of hyperglycaemia. There is no evidence for the optimal glucose lowering protocol. This study investigates the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GLP-1 (liraglutide, LG) treatment.

Detailed Description
-----------------
Diabetes mellitus is associated with poor outcome after surgery. The prevalence of diabetes in hospitalised patients is up to 40%, meaning that the anaesthesiologist will encounter a diabetes patient in the operating room on a daily basis. Multiple protocols for perioperative glucose regulation have been developed, ranging from intravenous glucose-insulin-potassium infusion to subcutaneous bolus regimens. Despite this abundance of published glucose lowering protocols and the proven negative effects of intraoperative hyperglycaemia in diabetes, there is no evidence regarding the optimal intraoperative glucose lowering treatment. 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 low incidence of hypoglycaemia. This study investigates for the first time the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus undergoing non-cardiac surgery. Objective: This study investigates the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GLP-1 (liraglutide, LG) treatment.

Official Title
-----------------
PILGRIM - Perioperative Insulin, GIK or GLP-1 Treatment in Diabetes Mellitus Type II

Conditions
-----------------
Diabetes Mellitus Type II

Intervention / Treatment
-----------------
* Drug: Liraglutide
* Drug: Insulin bolus
* Drug: GIK infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent known diabetes mellitus type II for > 3 months aged 18-75 years scheduled for elective non-cardiac surgery Exclusion Criteria: - Daily insulin dosage of > 1 IU/kg body weight Oral corticosteroid use Planned for day-care (ambulant) surgery Planned ICU stay post-operatively Planned bowel surgery History of chronic pancreatitis or idiopathic acute pancreatitis Impaired renal function defined as serum-creatinine ≥ 133 μmol/L for males and ≥ 115 μmol/L for females Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) Known or suspected allergy to trial product(s) or related products Any condition that the local investigator feels would interfere with trial participation or the evaluation of results

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BR (bolus regimen)<br>Day before surgery: half evening dose long acting insulin Day of surgery: patients using mealtime and longacting insulin/NPH: withhold mealtime morning dose, stop glucose lowering tablets patients using only long acting insulin/NPH: half dose of long-acting or NPH insulin, stop glucose lowering tablets Measure blood glucose every 60 minutes, start 30 min prior to surgery Give bolus of insulin according to treatment algorithm | Drug: Insulin bolus<br> <br> * Other names: novorapid;|
| Experimental: LG (Liraglutide)<br>Day before surgery: half dose of long acting and mealtime insulin from start liraglutide Day of surgery: withhold own insulin, stop oral glucose lowering tablets Start with 0.6 mg liraglutide subcutaneously (s.c.) the day prior to surgery at 17.00hr. In case of nausea graded higher than minimal, the patient will be excluded from the study Otherwise, treatment will be continued with 1.2 mg liraglutide s.c. per day on the day of surgery at 07.00hr. Measure glucose every 60 minutes, start 30 min prior to surgery Adjust according to bolus algorithm of BR group | Drug: Liraglutide<br> <br> * Other names: Victoza;Drug: Insulin bolus<br> <br> * Other names: novorapid;|
| Active Comparator: GIK (glucose -insulin - potassium) infusion<br>Day before surgery: half evening dose long acting insulin Day of surgery: stop oral glucose lowering tablets and withhold own insulin. GIK infusion: 500 cc glucose 5% with insulin and 10 mmol KCL per 500 cc. Start at 83 ml/hr. Calculate the insulin amount in the GIK infusion according to the formula: I= (PG-7)/(200/W)+8 I=Insulin amount, PG=glucose 30 minutes preoperative, W= body weight in kg Measure blood glucose every 60 minutes, start 30 min prior to surgery Adjust glucose > 8 mmol/l according to treatment algorithm | Drug: GIK infusion<br>* continuous infusion<br>* Other names: glucose, insulin, potassium infusion;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median glucose | The difference in median glucose between the GIK + BR and LG group 1 hour after surgery | 1 hour after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Insulin administration | The difference in insulin administration between the GIK + BR and LG group within 24 h after start of surgery | 1 day postoperative | 
| Median glucose | The difference in median glucose between the GIK + BR and LG group 4 hours and 1 day after surgery | 4 hours and 1 day postoperative | 
| Postoperative complications | The difference in proportion of any postoperative complication within the first month | 1 month after surgery | 
| Hypoglycemia | The occurrence of mild and severe hypoglycemia (glucose <4.0 mmol/l and <2.3 mmol/l, respectively) during and up to 24 h after surgery | From start treatment until the morning of day 1 postoperative | 
| Hypo- and hyperkalemia | The occurrence of hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) during and up to 24 h after surgery | from start treatment until morning of day 1 postoperative | 
| Glucose | the difference in median glucose 1hr preoperative, 1, 4 hours postoperative, 1 day postoperative between the three groups. | From start treatment until morning of day 1 postoperative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
glucose, diabetes mellitus, perioperative