View clinical trials related to Microvascular Disease.
Filter by:The goal of this study is to compare the impact of metabolic surgery and a class of anti-diabetes medications (Glucagon-like peptide-1 receptor agonists,GLP-1 RAs) on occurrence of diseases involving small and large vessels such as heart disease, kidney disease, and disease of the retina (a part of the eye), as well as deaths.
The evidence above demonstrates that microvascular dysfunction is an important determinant of patient prognosis, which however remains poorly classified. Given the high burden of disease and the severity of the functional impairment in these patients, the lack of a clear definition for this disease has a potentially large clinical importance. It is important to better describe the phenotype of these patients, identify the predictors of prognosis, and determine the impact of diagnosis.
Coronary artery disease (CAD) pathophysiology involves endothelium-dependent (e.g. nitric oxide, acetylcholine) and -independent (e.g. adenosine) vascular dilation impairment, which have been demonstrated at the level of small coronary arteries, medium sized peripheral arteries and subcutaneous microcirculation. Oxygen supplementation, which is frequently overused in clinical settings, seems harmful in acute coronary syndromes and increases microvascular resistance in myocardial and subcutaneous microcirculation through alteration of endothelium-dependent and -independent dilation by an oxidative mechanism. Whether endothelial dysfunction, that is well documented at the level of cardiac microcirculation in CAD patients, is also present at the level of subcutaneous microcirculation is unknown. Also, unknown is whether an acute oxidative stress can be used to probe myocardial microcirculatory dysfunction at the level of subcutaneous microcirculation, which is an easily accessible vascular bed for an in vivo assessment of endothelial-dependent and-independent function. Alterations in cutaneous vascular signalling are evident early in the disease processes. Thus, studying subcutaneous circulation in patients with cardiovascular risk factors could provide vascular information early in CAD processes. This study will test the following 4 hypotheses: 1. Endothelial dysfunction observed at the level of microvascular cardiac arteries is readily present at the level of subcutaneous microcirculation in a given CAD patient. 2. An acute oxidative stress such as hyperoxia can be used to test myocardial microcirculatory dysfunction at the level of the more easily accessible subcutaneous microcirculation. 3. Subcutaneous microcirculation of CAD patients has a lesser vasodilatory response to acetylcholine or sodium nipride than matched healthy subjects. In addition, CAD patients are more prone to dermal vasoconstriction in response to oxygen compared to healthy subjects. 4. Taken that oxygen is still too often given in excess in most clinical settings, the aim of this study is to rule out possible pitfalls in coronary pressure and resistance determinations in CAD patients receiving unnecessary oxygen supplementation.
Animal models have demonstrated that incretins have a glucose-independent effect on vascular perfusion, and there is limited evidence that incretins may enhance endothelial function in healthy subjects. Currently DPP-4 inhibition increases levels of the endogenous incretin Glucagon-like Peptide 1 (GLP-1) and is licensed for the treatment of hyperglycaemia in type 2 diabetes. They are positioned as third or even fourth line therapy after metformin, sulphonylureas ± glitazones, however recent analyses of cardiovascular outcomes in glitazones and sulphonylureas suggest at best they do not reduce cardiovascular endpoints, and may increase some outcomes. If the vascular benefits suggested in animal models are realised in humans this should see the DPP-4 inhibitors moved to second line and possibly 1st line. In order to realise the potential the investigators would like initially to demonstrate increases in vascular perfusion and function in a placebo controlled trial using accurate surrogates for vascular function in patients with insulin resistance and obesity. The investigators hypothesis is that by increasing incretin activity in insulin resistant states the investigators will lower capillary pressure and improve microvascular function, which will be accompanied by a reduction in macular thickness (by reducing macular oedema) and microalbuminuria, recognised surrogates for early diabetic retinopathy and renal failure respectively.