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Adiponectin in health and disease

Watt, Pauline Heather (2010) Adiponectin in health and disease. MSc(R) thesis, University of Glasgow.

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Abstract

The incidence of diseases associated with the metabolic syndrome has rapidly increased in recent years. The most common of these diseases is Type 2 Diabetes. Research into ways of alleviating the pathogenicity of Diabetes is ongoing, and the increase in diagnosis in recent years has motivated scientists to investigate novel risk markers to help predict and prevent Type 2 Diabetes Mellitus and the diseases associated with it. Adiponectin has become an important molecule in this search. Despite being released from adipose tissue, adiponectin correlates inversely with body fat in humans and animals. It also exhibits important metabolic regulatory functions such as glucose regulation and fatty acid catabolism and has been suggested to have anti-inflammatory properties. This thesis reviews literature on the adiponectin molecule and aims to explore the complex functioning of this adipokine and its relationship to Cardiovascular Disease (CVD) and Diabetes. The methodological considerations chapters focus on pre-analytical and analytical variables that may affect the collection of blood and the measurement of the molecule. We observed the molecule to be very stable. The measurement of both the high molecular weight (HMW) and total adiponectin species were not affected by up to 7 freeze thaw cycles. Furthermore, blood processing times and temperatures did not significantly alter results. Although the R&D systems adiponectin kits do not advise the use of citrated plasma, we validated its use in these kits and although absolute concentrations were lower than with EDTA plasma, they were consistently lower throughout the measured sample set. Two other commercial kits (Mercodia and ALPCO diagnostics) were tested for performance against the R&D systems Enzyme-Linked Immunosorbent Assay (ELISA) kit. Although there were differences between absolute values in each kit, the overall performance of the kits were satisfactory as judged by Bland-Altman plots. In the first of the two clinical associations chapters, we report, from a prospective study of older British women, no evidence of any association of HMW adiponectin (or its ratio to total adiponectin) with incident vascular events and suggest that circulating concentrations of adiponectin (and its fractions) may be more strongly aligned to the risk for Diabetes than to vascular events. The final study investigates the relationship between B-type natriuretic peptide (BNP) and adiponectin in Acute Coronary Syndrome (ACS) patients. Adiponectin and BNP are both known to be positively associated with risk of poor outcome, and with each other, in cross-sectional studies. However, serial changes in these parameters, following ACS, have not previously been measured. In this study, adiponectin and BNP positively correlated at baseline, 7 weeks, and importantly, change over 7 weeks in both parameters was significantly correlated. We reported that increases in plasma adiponectin (rather than absolute levels) after ACS are related to risk of adverse outcome, but that this relationship is not independent of BNP levels. Our results allude to a potential direct or indirect effect of BNP on adiponectin levels, post-ACS; an observation that requires further investigation. In summary, this thesis has shown adiponectin to be a very stable and robust analyte in plasma or serum, with good reproducibility within persons and broadly between differing assays. Whilst there are clear data linking low adiponectin with incident diabetes, our clinical studies show adiponectin has more complex associations with vascular disease, perhaps mediated in part by a complex interaction with BNP. Further genetic studies are needed to elaborate causal association for this complex molecule.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Keywords: Adiponectin, cardiovascular, biomarkers, Diabetes Mellitus, HMW Adiponectin, BNP, metabolic, epidemiology, inflammation
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Supervisor's Name: Sattar, Professor Naveed
Date of Award: 2010
Depositing User: Miss Pauline Heather Watt
Unique ID: glathesis:2010-2098
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 04 Oct 2010
Last Modified: 10 Dec 2012 13:51
URI: http://theses.gla.ac.uk/id/eprint/2098

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