Coronary Artery Disease and Diabetes Mellitus

Coronary Artery Disease and Diabetes MellitusIntroductionThe coronary thrombosis arterial bank line vessel supplies the crosscurrent to the heart muscles to enrich it with oxygen and other nutrients. It also carries deoxygenated phone line away from the heart. The coronary arteria consists of 2 main arteries the right coronary artery which supplies blood to the right ventricles and right atrium and the left coronary artery which supplies blood to the left ventricles and left atrium. The two many arteries further break up into two the left coronary artery divide into the circumflex artery which supplies blood to the back of the heart, the left anterior descending artery supplies blood to the mien of the heart the right coronary artery is divided into right nates descending artery and large marginal arteries and supply blood to the sinoatrial nodes that accommodate the heartrhythmic rate. The coronary arteries have 3 layers of tissues the tunica adventitia which covers the ou tside, the tunica media which is the middle layer and the tunica intima endothelium which is the inner layer. The diameters of the coronary arteries take to the woods from 0.6mm-4.4mm, any occluded front to any of these arteries that stops blood flow to the touch area take up to coronary artery disease (CAD). The normal blood glucose range is 4-6 mmol/L and 7.8mmol/L 2 hours after meal. This range is controlled by insulin which causes cells to absorb excess glucose in blood and glucagon which causes cells to release glucose from stores. Insulin is produced by the genus Beta cells of the islets of Langerhans of the pancreas. When blood glucose level rises above its normal range insulin binds to the extracellular subunits of its receptors (IRS-1 and IRS-2) on the cell surface which sends signals into the cell causing the intracellular proteins to alter their operation which in turn initiates the movement of glucose raptusers (GLU1-4, depending on the cell/tissues involved) to the cell membrane which then transports glucose into the cell where it may be further be born-again glycogen, the storage homunculus of glucose. Any impairment to the function of insulin, or its receptors claim to hyperglycemia and when excess of this glucose in bloodstream is passed in urine it results to diabetes mellitus. Diabetes mellitus hobo be classified into two main typefaces Diabetes mellitus type 1 (DM 1) and diabetes mellitus type 2 (DM 2). High sugar levels in blood (hyperglycemia) maybe collect(p) to insulin resistance in cases of type 2 diabetes or destruction of important cells of the pancreas in cases of type 1 diabetes, which downstream leads to CAD.Atherosclerosis which back end slip away in any part of the organic structure result from endothelia revile which can be caused by high blood pressure, smoking, genetics, age, gender, high blood glucose, freight gain etc. when atherosclerosis occurs in any of the coronary arteries it leads to coronary arte ry disease. Events leash to atherosclerosis include Endothelial damage which leads to rabble-rousing responses such(prenominal)(prenominal) as accumulation of white blood cells , low assiduousness lipoprotein (LDL)and high density lipoprotein (HDL), oxidation of LDL induced by resign radicals (reactive oxygen species), platelet aggregation, chemotaxis of macrophages, formation of foam cells, proliferation of smooth muscle cells (atheroma occurs), sinewy tissue and calcium salts cause the atheroma to harden this results in less ginger snap of the artery (atherosclerosis). All of these stock-stillts narrow the coronary artery from the normal physiologic range of 0.6-4.4mm (including small coronary arteries branching from the main arteries) to very little diameter depending on the level of narrowing and then blushtual blockage preventing or limiting blood and nutrient supply to heart tissues leading to death of affected heart tissues, heart attack or even death of the patient .According to statistics, diabetes and coronary artery disease are virtually related, this is because 50% of patients with diabetes are at risk of suffering CAD alongside. In the United States 77% cause of death is diabetic CAD. The prevalence of diabetes globally is change magnitude and its the major risk factor of other health check overs. The discipline Institute of Health reported that 65% of diabetic patients are much at risk of developing stroke, high blood pressure, obesity, kidney failure, and heart diseases such as cardiac arrest, myocardial infarction, and atherosclerosis in the heart (CAD) which when non optimally managed could lead to death.CAD and Diabetes MellitusThe cause of DM1 is unknown but studies ordinate it could be genetic or viral infection which leads to an autoimmune condition where the body defense mechanism destroys its cells, in this case the pancreatic important cells where insulin is produced. When the beta cells of the pancreas are destroyed, t he pancreas will no longer be competent to make insulin which downstream causes the bloodstream to be glucose logged due to in baron of the body cells to move glucose out of the bloodstream, leading to impaired insulin secretion, decreased signalling in the hypothalamus, summation food intake, weight gain and hyperglycemia, which downstream leads to atherosclerosis.DM 2 is due to the body cells inability to respond to insulin stimulation. Insulin resistance is due to obesity, age and inactive life style (irregular body activities), Age and sedentary lifestyle some(prenominal) lead up to increase in body weight (accumulation of fatty tissue). With or without hyperglycemia, insulin resistance can cause atherosclerosis, this results from change magnitude lipolysis of adipocytes leading to increased nonesterified fatty vitriolic secretion (NEFA), pro-inflammatory cytokines such as neoplasmP1521598xnecrosis factor-a (TNF-a), interleukin-6 (IL-6) and monocyte chemoattractant protei n-1 (MCP-1). NEFA can be deposited in and cause dysfunction of pancreatic beta cells, liver and skeletal muscles, all of which enhance insulin resistance and snub production of insulin. Accumulation of NEFA in skeletal muscle leads to competition with glucose for substratum oxidation thereby increasing the intracellular content of fatty acid metabolites such as diacylglycerol (DAG), fatty acyl coenzyme A and ceremide which together initiate serine/threonine kinase processes leading to insulin receptor substrate 1and 2 (IRS 1 IRS 2) phosphorylation, reducing their ability to undergo tyrosine phosphorylation and carry out their normal physiological function in insulin signalling.The final target of these receptors is the blockage of phosphatidylinositol 3-kinase (PI3) which is responsible for decreasing expression of aid molecules, NF-kb activation, Ros formation and increasing eNOS production. PI3 blockade leads to hyperstimulation of mitogen-activated protein kinase (MAP-kinase ) by increasing insulin production which contributes to vascular hypertrophy, hypertension, increased plasminogen activator inhibitor-1 (PAI-1) production and arrhythmias, all of these processes lead to endothelial lining damage which causes atherosclerosis.Diabetes and AtherosclerosisHyperglycemia can also lead this atherosclerosis because increase in blood glucose levels leads to increase in reactive oxygen species (ROS) because of mitochondrial dysfunction which is the initial event observed in hyperglycemia. Glycolysis generates nicotinamide adenine dinucleotide (NADH) and pyruvate. Pyruvate in tricarboxylic oscillation (TCA) generates moleculesof CO2, 4 NADH and 1 FADH NADH and FADH are electron carriers/donors in the electron transport chain which is made up of 4 complexes, I-IV). In mitochondria, NADH and FADH donate electron for generation of ATP. In hyperglycemia, there is increased glycolysis which leads to increased electron largess to the electron transfer chain (ETC) which increases electron flux raising potential drop crossways the membrane and generates higher membrane potential eventually reach a threshold where transport at complex III is blocked, increasing electron donation to O2 at complex III generating ROS, mostly superoxide anion (O-). Superoxide inactivates glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase which induces vascular injury via 4 main thoroughfares protein kinase C pathway, hexosamine pathway, advanced glycation endproducts and polyol pathway.ROS enhances atherosclerosis by blocking eNOS synthase which enhances production of other ROS peculiarly in endothelial cells and vascular muscle cells. Superoxide reacts with nitric oxide to form peroxynitrite which selectively inhibits prostacyclin (PGI2) disrupting its synthases iron-thiolate centre. PGI2 inhibition causes build-up of its precursor prostaglandin endoperoxide (PGH2) which induces vasoconstriction and endothelial dysfunction. In addition, PGH2 promotes the conversion of PGI2 to thromboxane A2 by thromboxane synthase which leads to platelet aggregation.Diabetes and Response to injuryEndothelial progenitor cells (EPC) and vascular endothelial growth factor (VEGF) are responsible for response to injury and hypoxia, both are lacking in diabetes, this makes repair of injury very silent enhancing atherosclerosis.Conclusion With or without hyperglycemia, DM leads to atherosclerosis which if it happened in the coronary artery lead to narrowing and eventual blockage of the coronary artery leading to CAD. In DM 1 it goes through hyperglycemia/mitochondrial dysfunction pathway whereas in DM 2 it goes through insulin resistance/lipolysis pathway even in slim individuals if there is unequal distribution of fat across the body, it interferes with insulins ability to suppress lipolysis leading to higher NEFA production. Whichever way, DM is likely to lead up to CAD (when atherosclerosis occurs in the coronary artery) and other diseases such as obesity, high blood pressure, kidney disease and heart attack. One matter that can be seen in the events leading up to CAD are positive feedback events, for example, ROS blocks eNOS synthase which enhances the production of more ROS.