When compared to selleck inhibitor placebo glucagon-like peptide-1 (GLP-1) caused no apparent effect on change in plasma glucagon concentrations from baseline.Serum non-esterified fatty acidsSerum non-esterified fatty acid (NEFA) concentrations are shown in Figure Figure7.7. Fasting NEFA concentrations were similar on both days (at t = 0 minutes: GLP-1: 0.66 �� 0.12 vs. placebo: 0.67 �� 0.14 mmol/l; P = 0.93). The nutrient infusion had no effect on NEFA. GLP-1 did not have a detectable effect on fatty acids (at t = 30 minutes: GLP-1: 0.66 �� 0.14 vs. placebo: 0.68 �� 0.14 mmol/l; P = 0.82, at t = 270 minutes: GLP-1: 0.51 �� 0.19 vs. placebo: 0.59 �� 0.18; P = 0.44, and AUC0-270 minutes: GLP-1: 166 �� 40 vs. placebo: 187 �� 48 mmol/l/minute; P = 0.21)Figure 7Serum non-esterified fatty acids.

When compared to placebo glucagon-like peptide-1 (GLP-1) caused comparable effects on NEFA.Relationships to glucose-loweringWhen the glycaemic response to nutrient infusion was greater, the magnitude of lowering that was observed during GLP-1 IV infusion was also increased (r2 = 0.38; P < 0.05) (that is, glucose-lowering was apparently dependent on the blood glucose). There was a trend for an association between the magnitude of glucose lowering and the APACHE II on the first study day (r2 = 0.31; P = 0.07). There was no association between glucose-lowering and glycated haemoglobin or body mass index (data not shown).DiscussionOur major observation is that an acute exogenous administration of GLP-1 (1.2 pmol/kg/minute) attenuates the glycaemic response to small intestinal nutrient infusion in critically ill patients with known type-2 diabetes.

This effect is attributable, at least in part, to relative insulin stimulation. While the study establishes that GLP-1 has the capacity to reduce glycaemia in this group, during GLP-1 infusion glycaemic excursions were limited to < 10 mmol/l in approximately 50% of patients. There was evidence that the glucose-lowering effect of GLP-1 was glucose-dependent (that is, the greater the glucose concentrations during placebo, the greater the reduction in glucose during GLP-1). Small intestinal nutrient did not suppress glucagon in critically ill patients with type-2 diabetes during either placebo or GLP-1 infusion.The dose of GLP-1 was selected based on previous studies [8,9,13,14]. In ambulant type-2 diabetics, GLP-1 at higher doses (2.

4 pmol/kg/minute) has a greater glucose-lowering effect, but is also associated with increased adverse effects, particularly nausea and vomiting [15]. Such adverse effects may, potentially, be less common in sedated Cilengitide patient receiving small intestinal feeding, as opposed to nutrient administered orally to alert subjects. In view of our observations the effects of GLP-1 (or its analogues) at greater doses and/or in combination with insulin merit evaluation [16,17]. The feeding regimen was also based on our previous study in which nutrient was administered via a postpyloric tube [8].