Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

Objective: Hyperglycemia is a major risk factor for a poor outcome after major surgery in patients with type 2 diabetes. Intensive insulin treatment aiming at normoglycemia can markedly improve the survival of critically ill patients, but the broad clinical application is limited by its practicability and the risk of hypoglycemia. Therefore, the glucose-lowering effect of the incretin hormone glucagon-like peptide 1 (GLP-1) was investigated in patients with type 2 diabetes after major surgery. Design: Randomised clinical study. Setting: A surgical unit of a university hospital. Patients and Measurements: Eight patients with type 2 diabetes (five men, three women; age, 49 +/- 15 yrs; body mass index, 28 +/- 3 kg/m(2); glycosylated hemoglobin, 8.0% +/- 1.9%), who had undergone major surgical procedures, were studied between the second and the eighth postoperative day with the intravenous administration of GLP-1 (1.2 pmol(.)kg(-1.)min(-1)) and placebo over 8 hrs, each administered in randomized order in the fasting state. C-reactive protein concentrations of 4.9 +/- 4.2 mg/dL indicated a systemic inflammation. Blood was drawn in 30-min intervals for glucose (glucose oxidase), insulin, C-peptide, glucagon, and GLP-1 (specific immunoassays). Statistics were done with repeated-measures analysis of variance and Duncan's post hoc tests. Main Results. During the intravenous infusion of GLP-1, plasma glucose concentrations were significantly lowered, reaching the normoglycemic fasting glucose range within 150 mins, but they remained elevated during placebo infusion (p < .001). The GLP-1 infusion led to a significant increase of insulin secretion (p < .001 for insulin and C-peptide) and a suppression of glucagon secretion (p = .041). No hypoglycemic events were recorded during the experiments. Conclusions: As far as can be concluded on the basis of our data with the infusion of GLP-1 over 8 hrs in eight patients, GLP-1 can be used to reduce glucose concentrations in patients with type 2 diabetes after major surgery.