Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/78873
Type: Thesis
Title: Glucose metabolism in the critically ill.
Author: Deane, Adam Matthew
Issue Date: 2012
School/Discipline: School of Medicine
Abstract: Hyperglycaemia occurs frequently in the critically ill, even in those without a history of diabetes, and is associated with adverse outcomes. While the gastrointestinal tract is pivotal in the regulation of glucose metabolism in health and diabetes, this relationship had not been explored in the critically ill. The focus of this thesis is glucose metabolism in the critically ill, with a particular emphasis on the role of the gastrointestinal tract in modulating blood glucose concentrations. The work submitted for this thesis comprises two studies validating methodologies and eight subsequent studies. In health, hormones secreted from the small intestine have the capacity to modulate gastric emptying. Studies were designed to further evaluate hormonal mechanisms underlying gastric emptying. The student established that in health endogenous glucagon-like peptide-1 (GLP-1) slows gastric emptying and glucose absorption, thereby attenuating postprandial glycaemia (chapter 4.2). In the critically ill, glucose absorption was quantified following small intestinal administration, and it was observed that absorption was markedly impaired when compared to health (chapter 5.2). Despite the reduction in glucose absorption, postprandial glycaemic excursions were sustained for longer in the critically ill, attesting to the marked disturbance in glucose disposal in this group. The current management of ‘feed-intolerance’ in the critically ill involves delivery of nutrient via a postpyloric catheter, or administration of a gastrokinetic drug during intragastric feeding. When comparing postpyloric and intragastric delivery of nutrient the student observed that the former route is associated with more rapid glucose absorption and exaggerated ‘early’ glycaemic excursions, but no clear increase in overall absorption (chapter 5.3). In clinical practice postpyloric delivery of nutrient is recommended because this technique can increase delivery of nutrient, which is assumed to equate to an improvement in nutritional outcomes. However, the observations from the student’s previous study challenge this premise. A further study showed that a single dose of erythromycin acutely increased small intestinal glucose absorption, but possibly reduced lipid absorption and slowed small intestinal transit (chapter 5.4). A series of studies examined the potential for a novel method to glucose-lowering in the critically ill by administering GLP-1 in pharmacological doses. It was shown that GLP-1 markedly attenuated the glycaemic response to small intestinal feeding in nondiabetic critically ill patients (chapter 6.2), but that this effect appeared to be more modest in those patients with pre-existing diabetes (chapter 6.3). The mechanisms underlying the glucose-lowering effects of exogenous GLP-1 in the former group were then studied in more detail (chapter 6.4). In the critically ill pharmacological doses of GLP-1 have insulinotropic and glucagonostatic properties. Furthermore, exogenous GLP-1 has the capacity to reduce the rate of carbohydrate absorption as a result of slowing gastric emptying when the latter ‘normal’, but not when it is delayed. In summary, the studies described in this thesis have yielded a number of novel and important insights. These include the mechanisms underlying glucose absorption in health, quantification of glucose absorption in the critically ill, and the use of a potentially novel therapy (GLP-1) to regulate glycaemia in the critically ill.
Advisor: Fraser, Robert John Lovat
Chapman, Marianne
Horowitz, Michael
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2012
Keywords: glucose; critical illness; nutrition; intensive care
Provenance: Copyright material removed from digital thesis. See print copy in University of Adelaide Library for full text.
Appears in Collections:Research Theses

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