Overproduction of intestinal chylomicrons (CM) has been proposed to contribute to fasting and post-prandial (PP) dyslipidemia and may accelerate the development of cardiovascular disease (CVD) during obesity, insulin resistance (IR) and diabetes. However, the impact of morphological changes in intestinal mucosa structure have not been investigated during IR and intestinal dyslipidemia. The first objective of this thesis was to characterize intestinal villi morphology and to determine whether a morphological relationship exists with enterocytic apoB48 (a marker of CM), and intestinal lymph secretion of apoB48 in the obese and IR JCR:LA-cp rat. The second objective was to assess the impact of n-3 PUFA supplementation on PP dyslipidemia in the JCR:LA-cp rat. Intestinal hypertrophy was observed in IR rats, corresponding to an increase in intestinal and lymphatic apoB48 expression. Further, a dietary intervention of n-3 PUFA showed lower PP plasma concentrations of apoB48 and PP plasma inflammatory markers. We conclude that intestinal hypertrophy may contribute to intestinal CM overproduction during obesity and IR. Additionally, dietary n-3 PUFA improves PP lipemia and the associated PP inflammatory response in the JCR:LA-cp rat model. / Nutrition and Metabolism

With the severity of cardiovascular disease (CVD) and the related mortality rate to this disease, new methods are necessary for risk assessment and treatment prior to the onset of the disease. The current paradigm in CVD risk assessment has shifted towards the multivariate approach over the individual use of traditional risk factors or lipid measurements. Through a combination of analytical techniques and multivariate statistical analysis, a novel method of cardiovascular risk assessment was developed. The analytical techniques employed include density gradient ultracentrifugation (DGU) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) applied to human serum. These techniques provided detailed information about the characterization of the lipoproteins and their structural components, specifically the apolipoproteins belonging to high density lipoproteins (HDL). This information when combined with multivariate statistical analysis provided a method that accurately identified the presence of CVD in clinical studies between cohorts of subjects that had been previously diagnosed with CVD and cohorts of subjects that had been identified as healthy controls (CTRL) based on a clear angiography. The lipoprotein density profiles were divided into subclasses based on their density and measured using a fluorescent probe to tag the lipoprotein particles. Use of multiple ethylenediaminetetraacetic acid (EDTA) based solutes allowed for the manipulation of the density gradient formation in order to separate the lipoproteins by specific density ranges in order to achieve better baseline separation of the profiles. Application of the integrated fluorescence intensities for each subclass of lipoprotein to linear discriminant analysis/sliced inverse regression (LDA/SIR) and quadratic discriminant analysis (QDA) yielded an advanced and accurate form of risk assessment for CVD. This method was found to be highly accurate as well as identify potential atherogenic lipoprotein subclasses through studying the LDA/SIR prediction equation generated. It was also shown that the LDA/SIR equation could be used to monitor medical treatment and lifestyle change for their effects on the risk assessment model. Further study into the atherogenicity of HDL through analysis of the apolipoproteins using MALDI-MS led to identification of potential risk factors that could be added to the statistical analyses. These risk factors included mass differences in the Apolipoprotein A-I (Apo A-I) and Apolipoprotein C-I (Apo C-I) between CVD and CTRL samples as well as the presence of specific mass peaks related to Apolipoprotein A-II (Apo A-II) that were primarily found in the CVD samples. These differences, in addition to the lipoprotein density profile data, were found to increase the potential accuracy of CVD risk assessment. The combination of these methods has shown great potential in the assessment of CVD risk as well as the ability to increase researchers' understanding of the nature of VD and how to treat it.

Background: Obstructive sleep apnea is a common disorder, especially in men. Patients with this condition often snore and suffer from excessive daytime sleepiness. It is a treatable condition related to cardiovascular disease, road traffic accidents and obesity. Aims: To study whether snoring and witnessed sleep apnea are related to diabetes mellitus and whether sleepy subjects who snore or report sleep apneas drive more than others. To investigate whether sleep apnea is related to stroke, mortality and myocardial infarction in patients with coronary artery disease. To study the effect of ambient temperature on sleep apnea, morning alertness and sleep quality in patients with obstructive sleep apnea. Methods and results: Questions on snoring, sleep apnea, daytime sleepiness and yearly driving distance were included in the northern Sweden component of the WHO MONICA study. Analyzed were 7905 randomly selected men and women aged 25-79 years. Snoring and witnessed sleep apnea were related to diabetes mellitus in women, (OR 1.58, p = 0.041 and OR 3.29, p = 0.012 respectively), independent of obesity, age and smoking, but not in men. Sleepy snoring men drove a mean of 22566 km per year which was more than others who drove 17751 km per year independent of age, BMI, smoking and physical activity (p = 0.02). Sleepy men reporting sleep apnea also drove more (p = 0.01). 392 men and women with coronary artery disease referred for coronary angiography were examined with overnight sleep apnea recordings and followed for 10 years. Sleep apnea was recorded in 211 (54%) of patients at baseline. Stroke occurred in 47 (12%) patients at follow up. Sleep apnea was associated with an increased risk of stroke (HR 2.89, 95% CI 1.37 - 6.09, p = 0.005) independent of age , BMI, left ventricular function, diabetes mellitus, gender, intervention, hypertension, atrial fibrillation, a previous stroke or TIA and smoking. The risk of stroke increased with the severity of sleep apnea. 40 patients with obstructive sleep apnea were investigated with overnight polysomnography in ambient temperatures of 16°C, 20°C and 24°C in random order. Total sleep time was a mean of 30 minutes longer (p = 0.009), sleep efficiency higher (p = 0.012), patients were more alert in the morning (p = 0.028), but sleep apnea was more severe when sleeping in 16°C (p = 0.001) and 20°C (p = 0.033) vs. 24°C. The AHI was 30 ± 17 in 16ºC room temperature, 28 ± 17 in 20°C and 24 ± 18 in 24°C. Conclusions: Snoring and witnessed sleep apneas are related to diabetes mellitus in women. Sleepy men who snore or report sleep apnea drive more than others. Sleep apnea is independently associated with the risk of stroke among patients with coronary artery disease. Subjects with obstructive sleep apnea sleep longer, are more alert in the morning after a night’s sleep, but sleep apnea is more severe when sleeping in a colder environment.

Doctor of Philosophy (PhD) / Introduction: The conventional approach to weight loss, recommended by almost all health authorities around the world, has been to reduce the total amount of fat in the diet and replace with carbohydrates. However, research trials using this approach have produced only modest results at best, and despite the active promotion of low fat eating and an apparent decline in fat consumption, rates of overweight and obesity have continued to climb. More recently low glycaemic index (GI) and high protein diets have become popular and are widely used by the public. However, only a small number of randomised controlled trials have been conducted and none directly comparing the two. Both approaches effectively reduce glycaemic load (GL) and aim to reduce post-prandial glycaemia and insulinaemia. This study aimed to evaluate the ability of diets with reduced GL to enhance the weight loss effects of a reduced-fat diet, to compare the two approaches of reducing GL on metabolic and anthropometric changes, and to investigate any benefit of combining both approaches to produce the lowest GL. Methods: We conducted a 12-week intervention in 129 overweight or obese young adults who were assigned to one of four diets with varying GL, protein, carbohydrate and GI, but similar fat (30% energy), fat type and fibre content. DIET 1 (highest GL) contained 55% E as carbohydrate; DIET 2 was a low-GI version of DIET 1; DIET 3 was a high protein diet with 25% E as protein; DIET 4 (lowest GL) was a low-GI version of DIET 3. The increase in protein in DIETS 3 and 4 came primarily from lean red meat. All key foods and some pre-prepared frozen meals were provided to maximise dietary compliance. Outcome measures were body weight, body fat, lean mass, waist circumference and the following blood parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerols (TAG), free fatty acids, C-reactive protein, fasting insulin, fasting glucose and leptin. Insulin resistance and β-cell function were assessed using homeostatic model assessment (HOMA) and the newer computer models HOMA2-insulin sensitivity and HOMA2-β-cell function. Results: While all groups lost similar amounts of weight (4.2 to 6.2% of initial weight, p=0.09), the proportion who lost >5% of body weight varied significantly by diet: 31%, 56%, 66% and 33% in groups 1, 2, 3 and 4 respectively (p=0.011). Differences were strongest in women (76% of the total group) who showed significant differences among groups in percentage weight change (-3.7 ± 0.6%, -5.7 ± 0.6%, -6.5 ± 0.5%, -4.1 ± 0.7% respectively, p=0.005) and fat loss (-3.1 ± 0.4kg, -4.9 ± 0.6kg, -4.8 ± 0.4kg, -3.6 ± 0.7kg respectively, p=0.007). Total and LDL-cholesterol increased on DIET 3 (high protein) compared to a fall on diet 2 (high carbohydrate/low-GI, p=0.013). TAG, HDL-cholesterol and glucose homeostasis improved on all four diets, with no effect of diet composition. Goals for energy distribution were not achieved exactly: both carbohydrate groups ate less fat and the diet 2 group ate more fibre. Conclusions: Reducing GL, through either substituting low-GI foods or replacing some carbohydrate with protein, improved the efficacy of a reduced-fat diet in women and in those with high TAG. Combining both approaches to produce the lowest GL did not promote further weight or body fat loss. Although weight loss was similar in all four diets for the group as a whole, overall clinical outcomes were superior on the high carbohydrate, low-GI diet.

The life expectancy (LE) gap experienced by Aboriginal and Torres Strait Islander peoples in one of Australians most enduring health divides. Whilst there are many likely reasons, cardiovascular diseases (CVD) stand as the primary contributor. In particular, it is the almost ten-fold higher mortality from CVD at young ages that distinguishes this epidemic. The reasons for this disparity remain incompletely understood. Current research has focused on the likely contribution of traditional risk factor burdens in Aboriginal people, who demonstrate higher levels of smoking, obesity, hypertension and dyslipidaemia. Less attention has focused on the potential contribution of disadvantage and its interplay with psychosocial factors. Research on the psychosocial determinants of health, particularly in relation to CVD, has a long pedigree. Social context, particularly inequality between individuals, has assumed its rightful place at the forefront of our understandings of population levels of disease. Among them, socioeconomic position [SEP] and depression are the most robust, and most widely researched. They have not been adequately explored in the context of Aboriginal Australians, nor has the manner in which culture shapes, sustains or transforms disadvantage and psychosocial stress been outlined. The objective of the Men Hearts and Minds (MHM) Study was to identify the possible ways in which social disadvantage may lead to CVD in Aboriginal men in Central Australia and consider the role of psychosocial factors in modifying or mediating this relationship. This required a detailed and multi-disciplinary plan of research, covering the epidemiology of mental illness and chronic diseases, biomedical science, ethnographic field work and qualitative methodologies. Stage I required the development of measurement tools for exploring depression, stress, resilience, mastery and socioeconomic indicators that were valid and robust for use with Aboriginal men within Central Australia. This involved multi-stage qualitative techniques, engaging Aboriginal men, traditional healers (Ngangkari Tjuta) and mental health experts, to define the expressions and construction of mental illness in Aboriginal men. Depression existed, was recognizable, common, and had profound impacts on the social, emotional and physical well-being of Aboriginal men. ‘Worry’ was the most recognisable element, and the principle contributor to depression in Aboriginal men. Much of this was focused on the increasingly heavy and cumulative social and cultural burdens experienced throughout Aboriginal men’s lives, and manifest as a sense of inner turmoil and questioning of self, and of feelings of disconnectedness from all the things of critical importance within their lives. Kurunpa [spirit] was seen as the foundation of vitality and was critical to the physical, emotional and spiritual well-being of Aboriginal people. These findings were then used to interrogate existing psychological testing tools and develop novel measures to explore the interplay of SEP, stress and depression. These tools were then used in a community dwelling sample of Aboriginal men in Central Australia to explore the interaction of SEP, stress and depression and their potential contribution to CVD risk. In total 186 Aboriginal men across urban and remote community settings were assessed. Almost 40% of the sample had elevated depressive symptoms. Depression was highly correlated with standard measures of distress and inversely with mastery. Newly created measures, assessing Chronic Stress, the ‘Sense of Injury’ and deprivation, were highly correlated, reliable and fulfilled many validity criteria. There was a high level of cardiovascular risk, which was related to a number of psychosocial factors, particularly depression. Major depression was over 9 times as common in individuals with prevalent CVD. Cardiovascular risk was patterned across social strata, but not evident with the use of routine measures of SEP. Psychosocial factors modified the observed social gradient. In those with high chronic stress, the social gradient in CVD risk gradient was amplified. This pattern was mirrored in those who had been removed or had family forcible removed. Depression was correlated with a number of atherogenic pathways. Smokers were more likely to be depressed, and depression was strongly related to obesity. Individual with high depression scores were more than 20 times more likely to have a Body Mass Index >30. The interplay between the Autonomic Nervous System (ANS) (estimated with measures of Heart Rate Variability) and the Hypothalamic Pituitary Adrenal (HPA) axis (as measured according to obesity) highlights the interconnections across atherogenic pathways and may frame the cardiometabolic risk and psychosocial pathways to cardiovascular disease in this sample. The phenomenology of cumulative stress, distress and depression within the narratives of Aboriginal men constructed illness as a consequence of the ongoing fight to maintain balance - physically, emotionally and spiritually. From both a social and biological perspective, the construction of depression and heart disease as a consequence of cumulative chronic stress among Aboriginal men was supported in the findings of this work.

[Truncated abstract] Current understanding of atherosclerosis suggests that it is a chronic inflammatory disease, and that increased oxidative stress may be an important pathological event contributing to the disease process. There has been interest in the ability of dietary derived nutrients such as vitamin E, to act as antioxidants and protect against atherosclerosis. Despite promising epidemiological data which suggested benefits from a higher intake of &alpha-tocopherol (&alphaT), one of the major forms of dietary vitamin E, for protection against atherosclerosis, large scale, randomised controlled trials have generally shown no protective effect of high dose &alphaT supplementation. Recent studies suggest that the other major dietary tocopherol isomer, &gamma-tocopherol (&gammaT), may possess biological activities not shared by &alphaT. Supplementation with &gammaT, or mixtures of tocopherols rich in &gammaT, have shown biological activities that may help protect against atherosclerosis. The aim of this PhD project is to further characterise the biological relevance of ?T for protection against CVD... Both ?- and mixed tocopherol supplementation resulted in reduced plasma F2-isoprostanes (P < 0.001 and P = 0.001, respectively) but did not affect 24 hour urinary F2-isoprostanes and erythrocyte antioxidant enzyme activities. Neither &alphaT nor mixed tocopherol supplementation affected any measured plasma markers of inflammation. The tocopherol supplementation also did not affect COX-2 activity as assessed by 14 stimulated whole blood prostaglandin E2 synthesis, and urinary prostacyclin metabolite output. Compared to the placebo group, stimulated neutrophil leukotriene B4 (LTB4) production decreased significantly in the mixed tocopherol group (P=0.02) but not in the &alphaT group (P=0.15). The ability of both pure &alphaT and mixed tocopherol supplementation to reduce systemic lipid peroxidation in patients with type 2 diabetes, suggests potential benefits of vitamin E supplementation in this population. However, despite decreasing oxidative stress, our results also suggests that in populations with well controlled type 2 diabetes, supplementation with either &alphaT, or mixed tocopherol rich in &gammaT, is unlikely to confer further benefits in reducing systemic inflammation. Future research into the possible unique biological activity of different tocopherol isomers other than &alphaT, for example, their ability to affect the 5-LO pathway and production of inflammatory mediators such as LTB4, is warranted.

Thesis (MNutrition (ITE))--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background Statins are drugs of known efficacy in the treatment of hypercholesterolaemia. However, statin-induced myopathy, an adverse effect of statins in up to 15% of its users, has warranted a reduction in the prescription dose or discontinuation of the drug. The exact mechanism of statin-induced myopathy is unknown, but the potential of Coenzyme Q10 (CoQ10) as treatment has been recognized due to decreased human plasma CoQ10 levels found after statin use and the concomitant role of CoQ10 in muscle function. Objectives This systematic review assessed the effect of CoQ10 supplementation on: the severity of statin-induced myopathic symptoms, levels of plasma creatine kinase, intramuscular and plasma CoQ10, as well as whether any adverse effects of CoQ10 supplementation such as abdominal pain, nausea and vomiting or headaches were experienced. Search methods Two searches for studies were conducted in The Cochrane Central Register of Controlled Trials (inception to March 2011 and inception to November 2011), MEDLINE (inception to March 2011 and inception to November 2011), Web of Science (inception to March 2011 and inception to November 2011), Science Direct (inception to March 2011 and inception to February 2012), Wiley Online Library (inception to March 2011 and inception to February 2012), Springerlink (inception to April 2011 and inception to February 2012), EBSCOhost [Academic Search Premier and CAB abstracts (inception to March 2011 and inception to February 2012), CINAHL (inception to March 2011 and inception to November 2011)], Scopus (inception to March 2011 and inception to November 2011) and Google Scholar (inception to March 2011 and inception to February 2012). Reference lists of articles were hand searched for relevant clinical trials. Only trials with a full text were included in the review. Selection criteria Randomised controlled trials (RCTs) were included with adult participants (mean of 18-64.99 years) of all race/ethnic groups and gender on statin therapy with reported myopathic symptoms from an unknown cause. The intervention was in the form of a pure oral supplement of CoQ10 irrespective of dose, duration and frequency, and the control in the form of a placebo, a similar antioxidant, or no intervention. Outcomes included the severity of myopathic symptoms, levels of plasma creatine kinase (U/L), intramuscular CoQ10 (μmol/kg) and plasma CoQ10 (μmol/L), as well as adverse effects of CoQ10. Data collection and analysis The principle investigator and one independent reviewer selected the studies, extracted data and assessed for risk of bias using the Cochrane Collaboration‘s tool for assessing risk of bias. Authors of relevant clinical trials were contacted for additional information. Results Two RCTs were included in the review, totaling 76 participants. A meta-analysis could not be performed, thus the review is narrative. There were an insufficient number of RCTs to confirm whether routine supplementation of CoQ10 improves statin-induced myopathic symptoms. Conclusions More and larger RCTs are required to determine the efficacy of CoQ10 supplementation in statin-induced myopathy. Consensus needs to be reached regarding the definition and measurement instrument/s of myopathy so that results of future studies can easily be compared and synthesized. / AFRIKAANSE OPSOMMING: Agtergrond Statiene is medikasie bekend vir die effektiewe behandeling van hipercholesterolemie. Statien-geïnduseerde miopatie is egter 'n newe-effek wat voorkom in tot 15% van gebruikers, wat 'n vermindering in die voorgeskrewe dosis of staking van die medikasie tot gevolg het. Die presiese meganisme van statien-geïnduseerde miopatie is onbekend, maar die potensiaal van Koënsiem Q10 (CoQ10) is geïdentifiseer as 'n moontlike behandeling aangesien menslike plasma CoQ10 vlakke verlaag na die gebruik van statiene en as gevolg van die rol van CoQ10 in spierfunksie. Doelwitte Hierdie sistematiese literatuuroorsig het die effek van CoQ10 supplementasie bepaal op: die graad van statien-geïnduseerde miopatiese simptome, plasma kreatien kinase vlakke, intra-muskulêre en plasma CoQ10 vlakke, asook die teenwoordigheid van enige newe-effekte van CoQ10 supplementasie soos abdominale pyn, naarheid en braking of hoofpyne. Soektogstrategie Twee soektogte vir studies is uitgevoer in The Cochrane Central Register of Controlled Trials (ontstaan tot Maart 2011 en ontstaan tot November 2011), MEDLINE (ontstaan tot Maart 2011 en ontstaan tot November 2011), Web of Science (ontstaan tot Maart 2011 en ontstaan tot November 2011), Science Direct (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012), Wiley Online Library (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012), Springerlink (ontstaan tot April 2011 en ontstaan tot Februarie 2012), EBSCOhost [Academic Search Premier en CAB abstracts (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012), CINAHL (ontstaan tot Maart 2011 en ontstaan tot November 2011)], Scopus (ontstaan tot Maart 2011 en ontstaan tot November 2011) en Google Scholar (ontstaan tot Maart 2011 en ontstaan tot Februarie 2012). Verwysingslyste van artikels is ook met die hand nagegaan vir relevante kliniese proewe. Slegs kliniese proewe waarvan die volteks beskikbaar was, is ingesluit in die oorsig. Seleksiekriteria Ewekansige gekontroleerde proewe (EGP) is ingesluit met volwasse deelnemers (gemiddeld 18-64.99 jaar) van alle rasse/etniese groepe en geslag op statien-terapie met gerapporteerde miopatie simptome van onbekende oorsaak. Die intervensie was 'n suiwer orale supplement van CoQ10 ongeag die dosis, duurte en frekwensie, en die kontrole 'n plasebo, soortgelyke antioksidant, of geen intervensie. Uitkomste het ingesluit: die graad van miopatie simptome, vlakke van plasma kreatien kinase (U/L), intra-muskulêre CoQ10 (μmol/kg) en plasma CoQ10 (μmol/L), sowel as newe-effekte van CoQ10. Dataversameling en -analise Die hoof ondersoeker en een onafhanklike hersiener het die seleksie van studies en data-ekstraksie onderneem en die risiko vir sydigheid geassesseer deur gebruik te maak van die Cochrane Collaboration’s tool for assessing risk of bias. Outeurs van relevante kliniese proewe is geraadpleeg vir addisionele inligting Resultate Twee EGP is ingesluit in die oorsig met 'n totaal van 76 deelnemers. 'n Meta-analise kon nie uitgevoer word nie, dus is die oorsig beskrywend. Daar was te min EGP om te bewys dat roetine supplementasie van CoQ10 statien-geïnduseerde miopatiese simptome verbeter. Gevolgtrekkings Meer en groter EGP is nodig om die effektiwiteit van CoQ10 supplementasie in statien-geïnduseerde miopatie te bepaal. Konsensus moet bereik word ten opsigte van die definisie en metingsinstrument/e van miopatie sodat die resultate van toekomstige studies makliker vergelyk en verwerk kan word.

OBJECTIVE: Our aim in this study to determine if serum uric acid level measured at baseline is a risk factor to develop Myocardial Infarction among people diagnosed with gout. METHOD: This was a retrospective cohort study, which used the THIN (The Health Improvement Network), an electronic medical records database from the UK. Obtained were SUA level at baseline after gout diagnosis and follow-up till time of event. We performed Cox proportional hazard regression models to examine the relation of SUA levels to risk of incident MI for men and women separately, and the multivariable regression model. RESULTS: There were 12,180 individuals included in this study, of them, 70% (n=8539) were men. There were 200 events of MI, 145 in men and 55 in women. SUA were not associated with risk of MI in unadjusted and adjusted multivariable regression model, the crude HR of MI in men were 1.27 (95% CI: 0.70-2.30), 0.97 (95% CI: 0.56-1.69), 0.83 (95% CI: 0.47-1.46), and 1.07 (95% CI: 0.62-1.84), respectively, for each increased SUA categories. No change observed after full adjustment. Similar results were also observed in women. CONCLUSION: There is no association between baseline SUA and risk of MI among gout patients.

End-stage renal disease patients have a greatly increased risk of cardiovascular disease partly attributed to the elevated levels of systemic inflammation observed in uraemia. One of the key mechanisms underlying inflammation appears to be the immune dysfunction that afflicts almost every aspect of the uraemic immune system. As a consequence patients experience immunosuppression and reduced responsiveness to antigen as well as a simultaneous over-activation leading to a pro-inflammatory environment. In addition, the haemodialysis (HD) treatment itself induces a proinflammatory response but may provide an otherwise opportune time to complete supervised exercise.

Cardiovascular disease contributes significantly to global morbidity and mortality and is particularly prevalent among individuals with Type 2 diabetes, which is thought to in part be due to the association between diabetes and the metabolic syndrome. Traditional cardiovascular risk prediction scores perform well in the general population but their use in people with Type 2 diabetes is limited as they are thought to underperform in high risk groups. Indeed, the use of any risk prediction in people with Type 2 diabetes is a point of discussion among clinicians as people with diabetes are thought by some to be at immediate high risk of CVD, whereas others view them as having a degree of modifiable risk which can be addressed using risk prediction. In the general population, novel markers such as cIMT and carotid plaque, as well as other potential biomarkers of cardiovascular risk, have been explored as possible adjuncts to risk scores in the prediction of cardiovascular disease. The evidence for their use in general populations has been established, although there have been no firm conclusions with regard to recommendations for their use, which is partly due to the high degree of variability in cIMT measurement. However, the evidence for their use in people with Type 2 diabetes is sparse, despite the use of such markers as surrogate CV endpoints in clinical trials. This thesis aimed to describe the frequency, distribution and change of cIMT and carotid plaque, as well as to explore the relationship of cIMT and carotid plaque with cardiovascular risk factors, prevalent cardiovascular disease and future cardiovascular events in older people with Type 2 diabetes. The association between cIMT, carotid plaque and other novel risk markers was also explored. The analysis was performed using data from the Edinburgh Type 2 Diabetes Study (ET2DS). This study is a large, prospective cohort study of 1066 men and women with Type 2 diabetes, aged 60-75 years at recruitment, living in Edinburgh and the Lothians. cIMT and carotid plaque were measured at year 1 follow up of the study. Variables concerning cardiovascular risk factors used in this thesis were obtained from the data collection performed at baseline and year 1. A mean of 3.5 years of follow up was available for analysis and is complete for the baseline cohort as data linkage was performed. Mean values of cIMT in the ET2DS were comparable with other studies of cIMT in people with Type 2 diabetes and may indeed be higher than cIMT in the general population. Measurement of cIMT by the sonographer was comparable with computer aided measurements. Increasing cIMT was independently associated (although only modestly) with increasing age, male sex and raised systolic blood pressure. Mean cIMT was associated with prevalent vascular disease and was predictive of incident global cardiovascular events and coronary artery events (but not stroke) over and above UKPDS risk factors, although the clinical impact of this on the reclassification of vascular risk (as demonstrated by net reclassification index (NRI)) was limited. There was a high prevalence of carotid plaque, and in particular “high risk” plaque, in the ET2DS. Different measures of carotid plaque were independently associated with several cardiovascular risk factors. Carotid plaque thickness was independently associated, albeit modestly, with increasing age, male sex, duration of diabetes and hypertension, plaque score with increasing age, hypertension, smoking and low BMI, and high risk plaque with hypertension and low BMI. All measures of carotid plaque were associated with prevalent vascular disease. However, despite these associations, carotid plaque did not have any additional predictive value for incident cardiovascular events over and above UKPDS risk factors. Finally, measures of cIMT and carotid plaque in the ET2DS were associated with the biomarkers ankle brachial index (ABI) and NTproBNP. In addition these markers were significantly higher in those individuals with prevalent vascular disease, suggesting a more extensive exploration of the association of these markers in relation to cardiovascular disease in the ET2DS may be warranted. cIMT and carotid plaque are modestly associated with traditional cardiovascular risk factors and prevalent cardiovascular disease in older adults with Type 2 diabetes. cIMT has been shown to be predictive of incident events while carotid plaque was not, in people with Type 2 diabetes, over and above traditional cardiovascular risk factors, although its impact on risk reclassification may only be small. Further evidence is required from the longer follow up of the ET2DS before firm conclusions can be drawn on the usefulness of cIMT and carotid plaque as risk markers in people with Type 2 diabetes. In addition, large collaborative studies could be used to further explore the relationship of carotid plaque, and change in cIMT with incident cardiovascular events, as well as exploring the additive effect of cIMT and plaque on risk prediction.