Incretins and the intensivist: what are they and what does an intensivist need to know about them?

Abstract

Hyperglycaemia occurs frequently in the critically ill, even in those patients without a history of diabetes. The mechanisms underlying hyperglycaemia in this group are complex and incompletely defined. In health, the gastrointestinal tract is an important modulator of postprandial glycaemic excursions and both the rate of gastric emptying and the so-called incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, are pivotal determinants of postprandial glycaemia. Incretin-based therapies (that is, glucagon-like peptide- 1 agonists and dipeptidyl-peptidase-4 inhibitors) have recently been incorporated into standard algorithms for the management of hyperglycaemia in ambulant patients with type 2 diabetes and, inevitably, an increasing number of patients who were receiving these classes of drugs prior to their acute illness will present to ICUs. This paper summarises current knowledge of the incretin effect as well as the incretin-based therapies that are available for the management of type 2 diabetes, and provides suggestions for the potential relevance of these agents in the management of dysglycaemia in the critically ill, particularly to normalise elevated blood glucose levels.

Figure 1

The incretin effect. There is a much greater release of insulin in response to oral glucose administration as compared with administering the same amount of glucose by intravenous (IV) infusion. Subjects were given oral glucose on day 1 with plasma insulin levels recorded. The same volunteers returned on a second day and an IV glucose infusion was titrated to match the plasma glucose excursion achieved with the oral load. The difference in the measured plasma insulin is the incretin effect, mediated by the hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Adapted from [17].

Figure 2

Glucose-lowering effect of glucagon-like peptide-1 in critical illness. In critically ill patients without known diabetes the blood glucose excursion in response to small intestinal feeding is markedly attenuated by 1.2 pmol/kg/minute glucagon-like peptide-1 (GLP-1) (area under the curve at 240 minutes: GLP-1, 2,077 ± 145 mmol/l/minute vs. placebo, 2,568 ± 208 mmol/l/minute; P <0.01). Data are mean ± standard error of the mean (n = 7). Reproduced with permission from [81].