Fatty acids and the modulation of glucose metabolism

• Main Author: Wakil, Ammar
• Other Authors: Atkin, Stephen : Kilpatrick, Eric
• Published: University of Hull 2011
• Subjects: 616.1; Medicine
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550477

Cardiovascular disease is the leading cause of death globally. This thesis has critically evaluated aspects related to two cardiovascular risk factors, namely hyperlipidaemia and hyperglycaemia, in healthy volunteers. Free fatty acids produced by visceral fat and transported to the liver in the portal circulation are thought to be one mechanism by which obesity contributes to increased insulin resistance and therefore reduced glucose disposal and a propensity to hyperglycaemia. The first study assessed the bioavailability of eicosapentaenoic acid, a cardio-protective fatty acid, in different forms of fish oil and then by incorporation with spores or exines. Potential use of the latter as a carrier of fatty acids to the portal circulation to increase insulin resistance and reduced glucose disposal was also studied. As short term plasma glucose fluctuations have been linked to an increased production of oxygen radicals, and thereby the microvascular complications of diabetes, a controlled assessment of this has been investigated in the final study. The first study examined in a double blind design the short term bioavailability, in the form of24 hour area under the curve, of eicosapentaenoic acid obtained from 5 forms of fish oil. The second study was an open label study which tested the change in the bioavailability of eicosapentaenoic acid in the form of ethyl ester by their incorporation with spores or exines. The latter was used in the third open label study to test whether the exines are capable of delivering what is inside them directly to the portal circulation. This could directly deliver oleic acid to the portal circulation thereby simulating the portal influx of farty acid from the central adipose tissue. In the final study, urinary isoprostane, a marker of oxidative stress, linked to the microvascular complications of diabetes was measured in three short term glycaemic states using the hyperglycaemic clamps in a cohort of healthy volunteers. This study aim was to establish whether glycaemic variability is associated with significant change in oxidative stress over and above that already present due to hyperglycaemia.