Exogenous glucagon-like peptide 1: a potentially novel therapy for the management of hyperglycaemia in the critically ill

Introduction

The purpose of this study was to determine the effects of exogenous glucagon-like peptide 1 (GLP-1) on the glycaemic response to enteral nutrition in nondiabetic, critically ill patients. Exogenous GLP-1 lowers blood glucose concentrations in both healthy humans and patients with type 2 diabetes, via suppression of glucagon, stimulation of insulin secretion and slowing gastric emptying. As the humoral effects are glucose dependent, the use of GLP-1 is not associated with hypoglycaemia. The effects of GLP-1 on glycaemia in critical illness have hitherto not been evaluated.

Methods

Seven, nondiabetic, critically ill patients (four males, three females; age 58 ± 6 years) received, on two separate days, intravenous GLP-1 (1.2 pmol/kg/min) or placebo between t = 0 and 270 minutes, in randomised double-blind fashion. Between t = 30 and 270 minutes a liquid nutrient was infused intra-duodenally at a rate of 1.5 kcal/min. Blood glucose, plasma insulin and glucagon concentrations were measured. Data are presented as the mean ± SEM. Statistical analyses were performed using the paired t test or repeated-measures ANOVA.

Results

Compared with placebo, GLP-1 decreased peak glucose concentrations (10.1 ± 0.7 mmol/l vs. 12.7 ± 1.1 mmol/l; P = 0.01) and markedly attenuated the overall glycaemic response to enteral nutrition (blood glucose area under the curve 30 to 270 min, 2,077 ± 145 mmol/l/240 min vs. 2,568 ± 208 mmol/l/240 min; P < 0.02) (Figure 1). GLP-1 caused a transient, but nonsustained, suppression of plasma glucagon concentrations (t = 30 min, 90 ± 12 pmol/ml vs. 104 ± 10 pmol/ml; P < 0.01) and tended to increase the plasma insulin/blood glucose ratio (between t = 0 and 270 min, mean Δinsulin/glucose ratio 5.0 ± 2.0 mU/mmol vs. 2.5 ± 0.9 mU/mmol; P = 0.12).

Figure 1

Glycaemic response to enteral nutrition is markedly attenuated (** P < 0.02).

Conclusion

Acute, exogenous GLP-1 infusion markedly attenuates the glycaemic response to enteral nutrition in the critically ill. Exogenous GLP-1 represents a potentially novel therapy for the management of hyperglycaemia in the critically ill.