The human stomach is a complex organ with sophisticated function. – The control of delivery of nutrients to the small intestine is tightly regulated, and the patterns and determinants of the associated processes are numerous, complex and interrelated. The presence of nutrients in the small intestine stimulates the release of a number of gastrointestinal hormones, including glucagon-like peptide-1 (GLP-1). Exogenous GLP-1 reduces fasting and postprandial glucose concentrations, and this is thought to be via a slowing of gastric emptying (GE). The effects of endogenous GLP-1 on GE and glycaemia were evaluated using exendin(9-39), a GLP-1 antagonist, in healthy subjects, in a randomised, placebo-controlled study, in Chapter 5. Exendin(9-39) increased postprandial glycaemia through an acceleration of GE; these findings support the putative role of GLP-1 as an enterogastrone. The capacity to measure GE has greatly increased the understanding of normal and disordered gastric physiology. 30 – 50 % of patients with longstanding diabetes have delayed GE. Scintigraphy remains the ‘gold standard’ in the measurement of GE, however, it is associated with a radiation burden. Recently, three-dimensional (3D) ultrasonography was validated against scintigraphy in healthy subjects. In Chapter 6, GE was measured concurrently by 3D ultrasonography and scintigraphy in patients with diabetic gastroparesis, and good correlation and agreement was found between both techniques. Glycaemic control represents one of the main pathogenetic factors of diabetic gastroparesis. Hyperglycaemia slows, while hypoglycaemia accelerates, GE in healthy subjects and patients with uncomplicated type 1 diabetes. Chapter 7 reports a study investigating the effects of insulin-induced hypoglycaemia vs. euglycaemia on GE in longstanding type 1 diabetes. Hypoglycaemia accelerated GE of a mixed solid/liquid meal; the magnitude of this acceleration was greater when GE during euglycaemia was slower. In contrast to glucose, the effects of intravenous (iv) fructose (used widely in the diabetic diet) on GE are less well understood. The comparative effects of iv fructose, glucose and saline on GE and antropyloroduodenal motility in healthy males are reported in Chapter 8. Compared with saline, fructose infusion was associated with a slowing of GE and suppression of antral waves, the magnitude of which was comparable to glucose. Treatment for the management of gastroparesis is currently suboptimal and there is a need for novel prokinetic agents. Itopride has demonstrated prokinetic activity in dogs. The effects of itopride on GE, glycaemia and upper gastrointestinal symptoms were studied in patients with longstanding diabetes in a randomised, placebo-controlled trial (Chapter 9). There was a trend for itopride to accelerate both solid and liquid GE. 48 % of patients had delayed solid and/or liquid GE on placebo, and in this group, itopride accelerated liquid, but not solid, GE. Autonomic neuropathy represents another pathogenetic factor of diabetic gastroparesis, and delayed GE is more prevalent in patients with autonomic dysfunction. There is evidence that C-peptide improves autonomic nerve function (ANF) in type 1 diabetes. The effects of C-peptide on GE and ANF were studied in patients with longstanding type 1 diabetes in randomised, placebo-controlled design, in Chapter 10. C-peptide had no effect on solid or liquid GE, or ANF. Gastroparesis, particularly in patients with diabetes, represents an important clinical problem. The studies presented in this thesis have provided fundamental insights into the measurement and determinants of gastric motor function and postprandial glycaemia, and treatment of gastroparesis, however, further studies which assess the complex pathogenesis and pathophysiology of gastroparesis, and which include a larger cohort of patients, are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1456472 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009
| Identifer | oai:union.ndltd.org:ADTP/285581 |
| Date | January 2009 |
| Creators | Stevens, Julie Eva |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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