perioperative intravenous insulin, GIK and GLP-1 treatment in diabetes mellitus

Diabetes mellitus is associated with poor outcome after surgery. The prevalence
of diabetes in
hospitalised patients is up to 40%, meaning that the anesthesiologist will
encounter a diabetic 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 hypoglycemia. This study investigates for
the first time the optimal intraoperative treatment algorithm to lower glucose
in patients with diabetes mellitus undergoing non-cardiac surgery.

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, insulin
bolus regimen and GPL-1 (liragludite) treatment.

Randomised Controled Trial

Before hospitalisation patients will be informed about the study. Informed
consent will be obtained the day before surgery. The participants will be
randomized to one of the three treatment groups: glucose-insulin-potassium
(GIK) group, bolus regimen group (BR) and the liraglutide group (LG). Subjects
randomised to the GIK group will receive a GIK infusion, and according to
glucose measurements a bolus insulin iv will be given according to the
algorithm of the BR group. For subjects in the BR group glucose will be
adjusted with boluses of insulin according to the algorithm. The subjects in
the LG group will receive 0,6mg liraglutide s.c. Treatment will be continued
with 1,2 mg liraglutide on the day of surgery. Glucose will be adjusted with
boluses of insulin according to the algorithm of BR. In all three groups,
glucose will be measured every 60 minutes starting 30 minutes prior to surgery
until discharge from the recovery .

Prior to surgery, HbA1C, potassium and starving glucose will be obtained. One
hour, 4 hours and 1 day postoperative blood glucose and potassium will be
measured in whole venous blood. Furthermore, prior to surgery and 4 hours after
surgery, one heparine, EDTA and citrate tube will be obtained for back-up
determinations. A total of 50 ml blood will be drawn for study purposus. Only
if the recovery stay exceeds 3 hours, extra glucose monitoring will be done via
fingerprick or blood withdrawal from existing arterial line. The glucose
monitoring during surgery and the first two hours postoperative is standerd
care.
Common adverse events with liraglutide treatment are related to the
gastrointestinal system, nausea and diarrhoea as reported most frequently.
Other adverse events include upper respiratory tract infections and headache.
All adverse events are mostly mild and the drop-out rate from clinical trials
due to adverse events has been low. Using blood glucose lowering agents, like
insulin and GLP-1 receptor agonists, there is always a risk of hypoglycaemia.
There will be extensive monitoring to prevent this adverse event. A possible
benefit is a better glycemic control during surgery and maybe a reduction in
postoperative complications.