Background: Obstructive Sleep Apnoea (OSA) is associated with cardiovascular disease. The current evidence regarding the effects of OSA in individuals with severe obesity is limited and has hitherto been largely unexplored. With the growing population of diabetes and obesity globally, the identification of severely obese individuals who have OSA is important given the risk of adverse outcomes associated with OSA. In this regard, the use of urinary proteomic (urinary peptide) profiling as a potential tool to characterise adult severely obese patients for the diagnostic assessment of OSA remains to be investigated. Aims: The aims of the studies described in this thesis were to (1) investigate the effects of OSA in severe obesity in relation to measures related to cardiovascular risk, specifically, arterial stiffness and serum urate; (2) assess current clinical practice of OSA assessment; and (3) explore the use of urinary proteomics in characterising subjects with severe obesity and OSA. Methods: In the arterial stiffness, urate and urinary proteomic studies, patients with severe obesity, were assessed at baseline and at follow-up. Anthropometric, respiratory and cardio-metabolic parameters were measured. All subjects had overnight polysomnography. Subjects with OSA were initially naive to OSA treatment at baseline were subsequently offered CPAP. For the arterial stiffness studies, pulse wave analysis (PWA) was performed. In the urate studies, serum urate measurements were taken to identify associations between OSA and urate at baseline; and CPAP with change in urate at follow-up. OSA assessment in diabetes clinical practice was explored by a national survey in relation to the International Diabetes Federation (IDF) guidance. In the urinary proteomics studies, urine samples were analysed by capillary electrophoresis-mass spectrometry (CE-MS) at baseline and at follow-up. Results: Severely obese patients with OSA had increased arterial stiffness. Although sleepiness and blood pressure improved with CPAP in severe obesity, CPAP alone was not sufficient to modify PWA measures to levels comparable with non-OSA patients. In the urate study, serum urate was associated with OSA in severely obese females and there was a trend for reduced urate levels in CPAP-treated patients. The questionnaire study revealed a disappointing low awareness of the IDF statements and of the perceived importance of assessing for OSA in type 2 diabetes. The urinary proteomic studies identified trends in the urinary peptide profiles suggesting that there may be inherent differences between OSA and non-OSA patients, even following a period of effective CPAP treatment. The identified peptide panel included collagens, cadherin and fibrinogen subtypes. Conclusions: The theme that links the studies in this thesis has been the importance of OSA in relation to cardiovascular risk. Severely obese patients with OSA have increased arterial stiffness that may increase cardiovascular risk. Likewise, in severely obese individuals with OSA who have hyperuricaemia or recurrent gout, there may be a need to consider OSA assessment as elevated urate levels are associated with increased cardiovascular risk. From the questionnaire study, it is clear that more work needs to be done to raise awareness about OSA assessment in diabetes teams as obesity is a risk factor for type 2 diabetes. Urinary proteomic CE-MS profiling has provided novel insights into the urinary proteome in OSA, with and without CPAP. Although there is insufficient evidence to support its use for OSA diagnosis, the urinary peptides identified may be linked with mechanisms underlying cardiovascular disease in OSA and may be associated with treatment effects of CPAP on OSA progression that influences expression of urinary peptides.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677488 |
| Date | January 2015 |
| Creators | Seetho, Ian |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://livrepository.liverpool.ac.uk/2017419/ |
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