Insulin Resistance, Type 2 Diabetes And Atherosclerosis
1Heart Institute (InCor), HCFMUSP- University of São Paulo Medical School, São Paulo, Brazil 2Federal University of Uberlândia, Brazil 3Faculty of Medicine ABC, Santo André, Brazil Citation: Roever L, Casella-Filho A, Dourado PMM, Resende ES, Chagas ACP (2014) Insulin Resistance, Type 2 Diabetes and Atherosclerosis. J Diabetes Metab 5:464. doi: 10.4172/2155-6156.1000464 Copyright: © 2014 Roever L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Journal of Diabetes & Metabolism Abstract Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity, glucose intolerance, metabolic syndrome and endothelial dysfunction), each of which is an independent risk factor for Cardiovascular Disease (CVD). Many prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes. Insulin resistance and lipotoxicity represent the missing links that help to explain the accelerated rate of CVD in type 2 diabetic patients. Accumulation of toxic lipid metabolites in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with diet, exercise and drugs mobilizes fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Keywords Glycemic control; Dyslipidemia; Cardiovascular risk; Epidemiology Int Continue reading >>
Type 1 Diabetes And Heart Disease Linked By Inflammatory Protein
NEW YORK, NY — Type 1 (insulin-dependent) diabetes appears to increase the risk of heart disease, the leading cause of death among people with high blood sugar, partly by stimulating the production of calprotectin, a protein that sparks an inflammatory process that fuels the buildup of artery-clogging plaque. The findings, made in mice and confirmed with human data, suggest new therapeutic targets for reducing heart disease in people with type 1 diabetes. Led by Columbia University Medical Center (CUMC) researchers in collaboration with investigators at New York University and the University of Pittsburgh, the study was published today in the online edition of Cell Metabolism. Diabetes is known to raise the risk for atherosclerosis, a disease in which fatty deposits known as plaque accumulate inside arteries. Over time, the arteries harden and narrow, leading to coronary artery disease and other forms of heart disease. Atherosclerosis is the leading cause of heart attacks, strokes, and peripheral vascular disease—collectively known as coronary heart disease, the leading cause of death in the United States. Scientists have known that diabetes leads to atherosclerosis. The study shows that this is associated with increased circulating levels of inflammatory white blood cells (WBCs), which contribute to the build-up of plaque. “But exactly how diabetes causes white blood cells to proliferate and lead to heart disease has been a mystery,” said study co-leader Ira J. Goldberg, MD, the Dickinson W. Richards Professor of Medicine at CUMC. In studies of mice with type 1 diabetes, Dr. Goldberg and his colleagues found that high blood sugar stimulates a type of inflammatory WBC known as neutrophils to release the protein calprotectin (also known as S100A8/9). The calprote Continue reading >>
Treating Type 1 Diabetes Treats Atherosclerosis
Treating Type 1 Diabetes Treats Atherosclerosis Treating Type 1 Diabetes Treats Atherosclerosis Pancreatic islet transplantation in type 1 diabetes may improve atherosclerosis. People with type 1 diabetes can face a number of complications, including narrowed arteries. Gaining better control of blood sugar levels can reduce their risk of these complications. According to recent research, transplanting pancreatic islet cells may improve narrowed arteries in patients with type 1 diabetes. The hardening and narrowing of the arteries called atherosclerosis is a common complication of diabetes. One marker of atherosclerosis is the thickness of the carotid arteries the vessels that carry blood to the head, neck and brain. Kristie K. Danielson, PhD, of the University of Illinois at Chicago, and colleagues found pancreatic islet transplantation reduced carotid artery thickness in patients with type 1 diabetes. The decrease in carotid artery thickness was associated with a decrease in levels of HbA1c. According to the studys authors, these findings suggest islet transplantation may improve diabetes-related atherosclerosis by improving blood sugar control in patients with type 1 diabetes. From their study of 15 patients with type 1 diabetes, Dr. Danielson and colleagues found carotid intima-media thickness decreased by about 0.058 mm 12 months after patients underwent islet transplantation. The decrease continued from 12 to 50 months after islet transplantation. Even though the thickness of the carotid artery is associated with atherosclerosis, thickening of the artery is not necessarily caused by atherosclerosis. However, once the carotid artery reaches a certain thickness, patients may almost certainly have atherosclerosis. This study did not show that islet transplantation pr Continue reading >>
Why Does Diabetes Increase Atherosclerosis? I Don’t Know!
Go to: Abstract There is a wealth of clinical data showing the relationship between diabetes mellitus and atherosclerosis and its clinical complications. To dissect this relationship, investigators have attempted, usually unsuccessfully, to create a small-animal model in which diabetes accelerates vascular lesion development. This effort has often been complicated by development of hyperlipidemia leading to difficulty in differentiating the effects of hyperglycemia from those of lipid abnormalities. A study in the current issue of the JCI provides data on a new mouse model in which atherosclerosis initiation is accelerated in diabetic mice and is reduced by insulin therapy. Moreover, these animals have greater intra-arterial hemorrhage, which might be due to less stable plaques . Go to: Animal models of diabetes and atherosclerosis For more than fifty years, researchers have attempted to create an animal model in which the human association of diabetes and accelerated atherosclerosis is reproduced. Administration of alloxan induced diabetes in rabbits; however, when these rabbits were fed an atherosclerosis-inducing high cholesterol diet, the effect on the diabetes was the opposite of what was expected. Diabetic rabbits had less atherosclerosis than the non-diabetic animals (5). Eventually the results of this experiment were understood when it was discovered that the large, lipid-rich particles produced by the intestines of the diabetic rabbits were unable to penetrate the vascular wall and provide the lipid environment needed to initiate the atherosclerotic process (6). Therefore, even if diabetes promotes inflammation, without vascular lipid deposition, there is no atherosclerosis. Go to: Mouse models of diabetic macrovascular disease Although the literature is not la Continue reading >>
How Hyperglycemia Promotes Atherosclerosis: Molecular Mechanisms
Abstract Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease. Atherosclerosis accounts for virtually 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized a major factor in the pathogenesis of atherosclerosis in diabetes. Hyperglycemia induces a large number of alterations at the cellular level of vascular tissue that potentially accelerate the atherosclerotic process. Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: 1) Nonenzymatic glycosylation of proteins and lipids which can interfere with their normal function by disrupting molecular conformation, alter enzymatic activity, reduce degradative capacity, and interfere with receptor recognition. In addition, glycosylated proteins interact with a specific receptor present on all cells relevant to the atherosclerotic process, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells. The interaction of glycosylated proteins with their receptor results in the induction of oxidative stress and proinflammatory responses 2) oxidative stress 3) protein kinase C (PKC) activation with subsequent alteration in growth factor expression. Importantly, these mechanisms may be interrelated. For example, hyperglycemia-induced oxidative stress promotes both the formation of advanced glycosylation end products and PKC activation. Advanced glycosylation end products The effects of hyperglycemia are often irreversible and lead to progressive cell dysfunction . For example, in diabetic patients with functioning pancreatic transplants renal pathology continues to progress Continue reading >>
Hyperglycemia And Endothelial Dysfunction In Atherosclerosis: Lessons From Type 1 Diabetes
International Journal of Vascular Medicine Volume 2012 (2012), Article ID 569654, 19 pages Departments of Cell Biology and Anatomy and Pathology, LSU Health Sciences Center, Shreveport, LA 71130, USA Academic Editor: Matthew R. Spite Copyright © 2012 Steven Daniel Funk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract A clear relationship between diabetes and cardiovascular disease has been established for decades. Despite this, the mechanisms by which diabetes contributes to plaque formation remain in question. Some of this confusion derives from studies in type 2 diabetics where multiple components of metabolic syndrome show proatherosclerotic effects independent of underlying diabetes. However, the hyperglycemia that defines the diabetic condition independently affects atherogenesis in cell culture systems, animal models, and human patients. Endothelial cell biology plays a central role in atherosclerotic plaque formation regulating vessel permeability, inflammation, and thrombosis. The current paper highlights the mechanisms by which hyperglycemia affects endothelial cell biology to promote plaque formation. 1. Cardiovascular Disease and Diabetes Mellitus Treatment of cardiovascular disease (CVD), manifesting in the form of myocardial infarction, stroke, and peripheral artery disease, represents one of biomedical sciences best success stories over the past several decades [1, 2]. Through clinical trials, epidemiology, and basic science, we have identified a host of risk factors and designed drugs targeting these risk factors that improve patient survival. The cholesterol-lowering stat Continue reading >>
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Heart Disease And Diabetes: An In-depth Look Into Atherosclerosis
Heart disease and diabetes: An in-depth look into atherosclerosis Heart disease and diabetes: An in-depth look into atherosclerosis To put this into perspective, a patient with type 2 diabetes in the UK is 56% more likely to die from a severe heart attack called ST elevation myocardial infarction. There is also a strong relationship between obesity and coronary heart disease risk factors . However, risk tolerance varies from one person to the next and, as we will discuss later in this article, managing certain modifiable risk factors can help reduce the riskof bad outcomes. Looking at the most nuanced scientific literature on cardiovascular disease, we have examined a number of recent compelling studies looking at the main drivers of atherosclerosis one of the most common diabetes-related heart disease complication and found that the atherosclerotic process is much more complex than it appears. The development and progression of atherosclerosis leading to plaque accumulation in arteries is multi-faceted and involves many biological processes, hence a multitude of arguments put forth by physicians for how it all begins and the ways to address it. When it comes to hypotheses for atherosclerosis , most of the research is also based on correlational data, so not all of them constitute valid actionable root causes per se. Atherosclerosis is an obstructive disease leading to plaque accumulation prompting gradual narrowing of the artery, with the eventual impaired control of flow, plaque rupture and thrombosis. There are multiple coincident factors that are implicated in the development and progression of metabolic syndrome-mediated heart disease. Atherosclerosis is a disease of compounding injuries involving multiple causative agents, so its important to understand the inter Continue reading >>
A disease in which arteries become dangerously narrowed by lipid deposits. People with diabetes are at increased risk for atherosclerosis. Atherosclerosis begins when the endothelium, the inner lining of the arteries that has direct contact with the bloodstream, becomes damaged. Over time, fats, cholesterol, fibrin (the principal component of blood clots), platelets, and calcium are deposited in the arterial walls. These materials form plaque, deposits that build up and narrow or block the arteries. Narrowing of the arteries can cause a number of problems. When atherosclerosis affects the coronary arteries, it can cause coronary heart disease, which in turn can cause angina or a heart attack. Angina pectoris, a type of chest pain, occurs when the heart cannot get enough blood and, hence, oxygen for a given amount of work. Chest pain can be a sign that someone is at risk for a heart attack. A heart attack, or myocardial infarction, occurs when blood flow to the heart muscle abruptly slows or stops. A blockage in the arteries that supply blood to the brain can result in a stroke. Atherosclerosis can also affect blood vessels in the rest of the body, a condition called peripheral vascular disease. Peripheral vascular disease is common in people with diabetes, and it can place them at risk for developing gangrene of the feet. One symptom of peripheral vascular disease is intermittent claudication, the “on-again-off-again” leg pain that occurs while walking but not at rest. The pain results when not enough blood and oxygen reach the exercising muscles. The risk factors for atherosclerosis include a sedentary lifestyle, advanced age (it is more common after age 50), a family history of heart disease, high levels of stress, and smoking. Other health conditions that raise o Continue reading >>
How Does Diabetes Cause Atherosclerosis?
Diabetes is known to cause a series of complications in the human body. It is a difficult condition and these complications caused due to diabetes make the disease even more difficult to manage. In today’s article, we shall learn more about one such condition called atherosclerosis caused due to inflammation and the disruption of blood vessels hindering the smooth flow of blood in different body parts. So, come and join in for the article “How Does Diabetes Cause Atherosclerosis? What is Atherosclerosis? Atherosclerosis is a condition in which the arteries become very narrow. The reason for the same is the deposits of too much of lipid in the arteries. The blood vessels of the body become very hard due to the above-mentioned lipid deposits. These deposits are also known as plaques and sometimes they even rupture the result of which is dangerous for the health of the individuals. How Can Diabetes Cause Atherosclerosis? Diabetes patients are exposed to higher chances of contracting atherosclerosis. There are various reasons for the same. The reasons are explained as below: The endotheliumis the inner lining of the arteries that are directly connected with the bloodstream. Atherosclerosis is caused when the endothelium is destroyed. The main reason behind this is the deposit of materials such as fat, cholesterol, fibrin, etc. resulting in the formation of plaque. In a normal healthy individual, endothelium helps the smooth functioning of the blood with the help of nitrous oxide that it itself produces. The nitrous oxide so produced performs the important function of helping the muscles to relax while also helping the cells to keep away from the walls of the arteries and not stick to them. Now, when a person suffers from a chronic illness like diabetes, the formation of Continue reading >>
How Can Diabetes Cause Atherosclerosis?
Atherosclerosis is a form of hardening of the blood vessels, caused by fatty deposits and local tissue reaction in the walls of the arteries. Blood supply beyond the affected parts of the artery is usually compromised by the narrowing and, sometimes, occlusion of the artery. The deposits, called plaques, may rupture with disastrous consequences. Diabetes mellitus is a documented high risk factor for the development of atherosclerosis. Heart disease and stroke, arising mainly from the effects of atherosclerosis, account for 65 percent of deaths among diabetics. Other complications of diabetes, such as blindness, gangrene and kidney disease, all have some deficiency of blood supply in their genesis. Video of the Day Normal blood vessels have an inner lining, called endothelium, that keeps blood flowing smoothly by producing local Nitrous oxide (NO). NO serves to relax the smooth muscles in the walls of the vessels and prevent cells from sticking to the walls. A disruption of this mechanism is thought to be at the heart of the increased formation of plaques in diabetes. High blood sugar, elevated fatty acids and triglycerides leads to stickier walls, encouraging the attachment of cells that produce local tissue reaction. The local tissue reaction further traps floating particles and different blood cells, heaping up and hardening the vessel walls. Insulin stimulates the production of NO by the cells lining the blood vessels. In diabetics who are resistant to the actions of insulin, this stimulatory effect is lost, resulting in increased tendencies towards plaque formation. In the presence of raised blood sugar and resistance to insulin, the lining cells of the blood vessels not only reduce production of NO, they also increase the production of substances that constrict the Continue reading >>
Does Insulin Cause Atherosclerosis (hardening Of The Arteries)?
Every time we eat a sugar or a simple carbohydrate, the body produces insulin. For example, if you eat a donut, the body responds by making more insulin to lower blood sugar. Not only does insulin itself cause weight gain in the mid?line and damage to the lining of the arteries, but high insulin levels, combined with high blood sugar levels, can lead to a hardening of the arteries. High blood sugar levels cause proteins in the inner lining of blood vessels to become sticky and to accumulate in the blood. These sticky proteins form plaques in the walls of the arteries. LDL, or "bad," cholesterol particles enter this sticky wall and cause the blood vessel to narrow, restricting blood flow. When plaque develops in the arteries, high blood sugar levels increase the likelihood that the plaque may break off and cause a clot, which could block the vessel and cause a stroke. Diabetics should try to choose foods that do not increase insulin level. For example, an apple will not increase the body's insulin level, but apple juice will. If a person's insulin level increases, the level of blood sugar will drop very low, causing the individual to crave more sugar—resulting in a cycle that keeps a person eating more and more carbohydrate?rich foods to soothe that craving. Eating foods that are light in carbohydrates and won't increase insulin levels helps prevent hardening of the arteries, mid?line weight gain, and—ultimately—can lower the risk factor for heart disease and stroke. Articles Questions Videos Important: This content reflects information from various individuals and organizations and may offer alternative or opposing points of view. It should not be used for medical advice, diagnosis or treatment. As always, you should consult with your healthcare provider about you Continue reading >>
Diabetes And Atherosclerosis: Is There A Role For Hyperglycemia?
Go to: STUDIES ON ISOLATED VASCULAR CELLS SUGGEST THAT ELEVATED GLUCOSE LEVELS CAUSE A PLETHORA OF PROATHEROGENIC RESPONSES, BUT THE IN VIVO RELEVANCE OF MOST OF THESE FINDINGS AWAIT VERIFICATION Although in vitro studies have provided important insights into potential mechanisms by which glucose might damage arterial cells or play a role in atherogenesis, these studies suffer from the shortcoming that they usually examine a single mechanism in isolation, and often provide different results from those obtained with in vivo studies. Numerous studies have attempted to evaluate the role of high glucose conditions on cells of the artery wall, including endothelial cells, smooth muscle cells, and macrophages. It has been proposed that glucose might act directly, or indirectly via the generation of advanced glycation end-products (AGEs) or reactive oxygen species. High glucose concentrations have been shown to lead to diacylglycerol accumulation and protein kinase C activation in vascular cells, and to increased glucose flux through the aldose reductase pathway. These pathways have been linked to increased inflammation via increased nuclear factor κ-B activation, for example. The most well-described glucose-induced pathways have been reviewed in detail elsewhere (7, 8), and are therefore not further covered here. Atherosclerosis is initiated by the adhesion of monocytes to arterial endothelial cells, followed by their transmigration into the subendothelial space along a chemotactic gradient. One mechanism by which high glucose conditions may enhance this process involves activation of NFκB (9, 10), which leads to the expression of several inflammatory genes, including adhesion molecules that facilitate monocyte adhesion to endothelial cells (9). Monocytes then differentiate Continue reading >>
Predicting Atherosclerosis Disease In Patients With Diabetes
Home / Conditions / MODY/LADA / Predicting Atherosclerosis Disease in Patients With Diabetes Predicting Atherosclerosis Disease in Patients With Diabetes Carotid ultrasound shows atherosclerotic disease is not just a concern for patients with type 1 and type 2 diabetes, but LADA as well. Approximately 4-14% of patients originally diagnosed with type 2 diabetes are reclassified as having latent autoimmune diabetes of adults (LADA). It is well known that macrovascular disease is the leading cause of morbidity and mortality in patients with type 1 and type 2 diabetes. However, little is known about the cardiovascular risks associated with patients diagnosed with LADA. Early diagnosis and treatment of carotid atherosclerosis greatly reduces a patients chances of experiencing a cardiovascular event. Although controversy surrounding the use of carotid ultrasound in the detection of preclinical atherosclerosis remains, it still proves to be a safe, non-invasive, and efficient way to evaluate the narrowing of the carotid arteries. A recent cross-sectional analysis, published in Cardiovascular Diabetology, evaluated carotid atherosclerotic disease in patients with type 1 diabetes, type 2 diabetes, and LADA. Researchers recruited 116 with type 1 diabetes, 191 patients with type 2 diabetes, and 71 patients with LADA. The study cohorts were similar in gender distribution, age, smoking status, HbA1c, and the use of antihypertensive medications. All study participants had a urine albumin-to-creatinine ratio less than 300 mg/dg and an estimated glomerular filtration rate greater than 60mL/min/1.732. Although patients were matched according to age, the duration of diabetes varied amongst the three groups. Patients with type 1 diabetes had the longest duration of disease followed by pa Continue reading >>
Diabetes And Your Heart
If you have diabetes, you are more likely to develop coronary heart disease than someone without diabetes. Diabetes causes high levels of glucose in your blood. This is because of a problem with a hormone your pancreas produces called insulin. Insulin is responsible for moving glucose (a type of sugar) from your bloodstream and into the cells of your body for energy. If there little or no insulin being produced, or your body has become resistant to insulin, glucose stays in the bloodstream and can’t move across to your cells to give them energy to work properly. High levels of glucose in your blood can damage the walls of your arteries, and make them more likely to develop fatty deposits (atheroma). If atheroma builds up in your coronary arteries (the arteries that supply oxygen-rich blood to your heart) you will develop coronary heart disease, which can cause angina and heart attack. Types of diabetes Type one diabetes happens when your body cannot make insulin. This type most commonly affects children and young adults, and is a result of your body’s immune system attacking the cells that produce insulin in the pancreas. Type two diabetes occurs when your pancreas isn’t producing enough insulin or your body has become resistant to the insulin it’s producing. Type two diabetes is much more common than type 1 and tends to develop gradually as people get older – usually after the age of 40, but more and more people every year are being diagnosed at a much younger age. It's closely linked with: being overweight, especially if you carry weight around your middle being physically inactive a family history of type 2 diabetes. Some ethnic groups have a much higher rate of diabetes - particularly people of South Asian and African Caribbean origin. Diabetes and your he Continue reading >>
Review Vascular Complications Of Diabetes: Mechanisms Of Injury And Protective Factors
In patients with diabetes, atherosclerosis is the main reason for impaired life expectancy, and diabetic nephropathy and retinopathy are the largest contributors to end-stage renal disease and blindness, respectively. An improved therapeutic approach to combat diabetic vascular complications might include blocking mechanisms of injury as well as promoting protective or regenerating factors, for example by enhancing the action of insulin-regulated genes in endothelial cells, promoting gene programs leading to induction of antioxidant or anti-inflammatory factors, or improving the sensitivity to vascular cell survival factors. Such strategies could help prevent complications despite suboptimal metabolic control. Continue reading >>