Atherosclerosis Pathophysiology News On The Ndc Channel
Interleukin-1Receptor Antagonist in Type 2 Diabetes Mellitus (NEJM 356:1517-1526, 2007)Background The expression of interleukin-1receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1 in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis. Methods In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemiceuglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were changes in beta-cell function, insulin sensitivity, and inflammatory markers. Results At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drug-related serious adverse events. Conclusions The blockade of interle Continue reading >>
Atherosclerosis
For the journal, see Atherosclerosis (journal). Atherosclerosis is a disease in which the inside of an artery narrows due to the build of plaque.[7] Initially there are generally no symptoms.[1] When severe it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems depending on the arteries which are affected.[1] Symptoms, if they occur, generally do not begin until middle age.[3] The cause is not known.[1] Risk factors include high blood pressure, diabetes, smoking, obesity, family history, and an unhealthy diet.[3] Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood.[7] The narrowing of arteries limits the flow of oxygen-rich blood to parts of the body.[7] Diagnosis is based upon a physical exam, electrocardiogram, and exercise stress test among others.[8] Prevention is generally by eating a healthy diet, exercise, not smoking, and maintaining a normal weight.[4] Treatment of established disease may include medications to lower cholesterol such as statins, blood pressure medication, or medications that decrease clotting, such as aspirin.[5] A number of procedures may also be carried out such as percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy.[5] Atherosclerosis generally starts when a person is young and worsens with age.[2] Almost all people are affected to some degree by the age of 65.[6] Atherosclerosis is the number one cause of death and disability in the developed world.[9] Atherosclerosis was first described in 1575.[10] There is evidence, however, that the condition occurred in people more than 5,000 years ago.[10] Play media Video explanation Definitions[edit] The following terms are similar, yet distinct, in both spelling and meaning, and can Continue reading >>
13g.v. Shrikhande And J.f. Mckinsey (eds.), Diabetes And Peripheral Vascular Disease: Diagnosis And Management, Contemporary Diabetes, Doi 10.1007/978-1-62703-158-5_2, © Springer Science+business Media New York 2012
Introduction Patients with diabetes mellitus (DM) have an over tenfold risk for cardiovascular disease in their life- time [ 1 ] . In the United States, 77% of diabetes- related hospital admissions are for cardiovascular complications. A key feature of diabetes contribut- ing to this is the development of an accelerated ath- erosclerosis [ 2 ] . Cardiovascular disease is one of the most morbid complications of DM with men and women being equally at risk, essentially eliminating the protection against cardiovascular disease char- acteristic of premenopausal women. DM predis- poses to higher rates of coronary artery disease (CAD), cerebral vascular disease, and peripheral arterial disease (PAD). Aggressive blood sugar con- trol has been shown to decrease some cardiovascu- lar sequelae in diabetics, particularly in type I DM; however it does not eliminate all risk and intensive glycemic control for type II diabetics has not proven to be bene fi cial and may even be detrimental [ 1, 3 ] . CAD is the most morbid cardiovascular com- plication of DM with a two- to fourfold increased risk [ 4 ] . Compared to cardiovascular disease in nondiabetics, diabetic patients have a greater overall coronary plaque burden and a higher rate of multivessel disease. The proportion of stenotic segments is directly proportional to the duration of disease [ 5 ] . In combination, these factors place diabetic patients at greater risk for myocardial infarction (MI). In fact, diabetics without a prior MI are at equal risk for MI as nondiabetics with a prior MI. After MI, complications and death are higher in DM. The increased risk also extends to those undergoing cardiac procedures. After percu- taneous coronary intervention (PCI), diabetic patients are at both higher risk for death and need for rei Continue reading >>
- Diagnostic accuracy of resting systolic toe pressure for diagnosis of peripheral arterial disease in people with and without diabetes: a cross-sectional retrospective case-control study
- Mastery in Diabetes Management: New Diabetes Diagnosis Criteria Req'd for Asian Patients?
- Complicated urinary tract infections associated with diabetes mellitus: Pathogenesis, diagnosis and management
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 >>
Diabetes And Atherosclerosisepidemiology, Pathophysiology, And Management
ContextComplications of atherosclerosis cause most morbidity and mortalityin patients with diabetes mellitus. Despite the frequency and severity ofdisease, proven medical therapy remains incompletely understood and underused. ObjectiveTo review the epidemiology, pathophysiology, and medical and invasivetreatment of atherosclerosis in patients with diabetes mellitus. Data SourcesUsing the index terms diabetes mellitus, myocardial infarction, peripheral vasculardiseases, cerebrovascular accident, endothelium, vascular smooth muscle, platelets, thrombosis, cholesterol, hypertension, hyperglycemia, insulin, angioplasty, and coronary artery bypass, wesearched the MEDLINE and EMBASE databases from 1976 to 2001. Additional datasources included bibliographies of identified articles and preliminary datapresented at recent cardiology conferences. Study SelectionWe selected original investigations and reviews of the epidemiology,pathophysiology, and therapy of atherosclerosis in diabetes. We selected randomized,double-blind, controlled studies, when available, to support therapeutic recommendations.Criteria for data inclusion (168 of 396) included publication in a peer-reviewedjournal or presentation at a national cardiovascular societysponsoredmeeting. Data ExtractionData quality was determined by publication in peer-reviewed literature.Data extraction was performed by one of the authors. Data SynthesisDiabetes mellitus markedly increases the risk of myocardial infarction,stroke, amputation, and death. The metabolic abnormalities caused by diabetesinduce vascular dysfunction that predisposes this patient population to atherosclerosis.Blood pressure control, lipid-lowering therapy, angiotensin-converting enzymeinhibition, and antiplatelet drugs significantly reduce the risk of ca Continue reading >>
Role Of Diabetes In Atherosclerotic Pathogenesis. What Have We Learned From Animal Models? - Sciencedirect
Volume 32, Issue 1 , February 2006, Pages 15-29 Role of diabetes in atherosclerotic pathogenesis. What have we learned from animal models? Get rights and content Diabetes mellitus is associated with a greater risk of developing atherosclerosis and its complications: stroke, myocardial infarction, and peripheral vascular disease. In patients with diabetes, atherosclerosis represents a complex multifactorial disease with increased lesion progression and severity compared to the nondiabetic population. Several risk factors have been proposed to explain the increased risk of cardiovascular disease with diabetes. They include: hyperglycae-mia, dyslipidemia, accelerated formation of advanced glycation end-products (AGEs), increased oxidative stress, and genetic factors. It is difficult to precisely establish the elements leading to diabetes-accelerated atherosclerosis by means of epidemiological studies because all these factors coexist in diabetic patients. Thus, diabetic animal models that reproduce exacerbation of atherosclerosis would be helpful to understand why atherosclerosis is accelerated by diabetes, and to design appropriate treatments to limit its progression. This review analyzes most of the animal models developed to reproduce diabetes-accelerated atherosclerosis, and summarizes the effects of hyperglycaemia and lipid abnormalities on atherogenesis. Rle du diabte dans la pathogense de l'athrosclrose. Qu'avons-nous appris des modles animaux ? Le diabte est associ une augmentation du risque de dvelopper des lsions d'athrosclrose et leurs complications: accident vasculaire crbral, infarctus du myocarde et atteinte vasculaire priphrique. Chez les patients diabtiques, l'athrosclrose est une maladie complexe et multifactorielle. Les lsions s'aggravent plus rapidement Continue reading >>
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 >>
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 [8]. For example, in diabetic patients with functioning pancreatic transplants renal pathology continues to progress Continue reading >>
Diabetes And Vascular Disease
Diabetes mellitus affects approximately 100 million persons worldwide.1 Five to ten percent have type 1 (formerly known as insulin-dependent) and 90% to 95% have type 2 (non–insulin-dependent) diabetes mellitus. It is likely that the incidence of type 2 diabetes will rise as a consequence of lifestyle patterns contributing to obesity.2 Cardiovascular physicians are encountering many of these patients because vascular diseases are the principal causes of death and disability in people with diabetes. The macrovascular manifestations include atherosclerosis and medial calcification. The microvascular consequences, retinopathy and nephropathy, are major causes of blindness and end-stage renal failure. Physicians must be cognizant of the salient features of diabetic vascular disease in order to treat these patients most effectively. The present review will focus on the relationship of diabetes mellitus and atherosclerotic vascular disease, highlighting pathophysiology and molecular mechanisms (Part I) and clinical manifestations and management strategies (Part II). Pathophysiology of Diabetic Vascular Disease Abnormalities in endothelial and vascular smooth muscle cell function, as well as a propensity to thrombosis, contribute to atherosclerosis and its complications. Endothelial cells, because of their strategic anatomic position between the circulating blood and the vessel wall, regulate vascular function and structure. In normal endothelial cells, biologically active substances are synthesized and released to maintain vascular homeostasis, ensuring adequate blood flow and nutrient delivery while preventing thrombosis and leukocyte diapedesis.3 Among the important molecules synthesized by the endothelial cell is nitric oxide (NO), which is constitutively produced by end Continue reading >>
- Treating gum disease may lessen the burden of heart disease, diabetes, other conditions
- American Diabetes Association® Releases 2018 Standards of Medical Care in Diabetes, with Notable New Recommendations for People with Cardiovascular Disease and Diabetes
- Diabetes and eye disease: How diabetes affects vision and eye health
Immune Mechanisms In Atherosclerosis, Especially In Diabetes Type 2
Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1β (IL-1β), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglyce Continue reading >>
(pdf) Diabetes And Atherosclerosis
eases of coronary arteries, peripheral ar- teries, and carotid vessels, particularly lation. Despite this challenge, many pri- strategies. The traditional therapeutic ap- lin secretion, because these patients rep- coronary arteries, lower extremities, and extracranial carotid arteries. Diabetes in- creases the incidence and accelerates the Author Affiliations: Leducq Center for Cardiovascu- lar Research, Cardiovascular Division, Department of Medicine, Brigham and Womens Hospital; and Har- Financial Disclosures: Dr Creager has been a consul- tant for Bristol-Myers Squibb/Sanofi-Synthelabo Part- nership, Pfizer, Otsuka America Pharmaceuticals, ENOS Pharmaceuticals, and Eli Lilly; has been on the speak- ers bureau of Bristol-Myers Squibb/Sanofi- Synthelabo Partnership, Pfizer, and Otsuka America Pharmaceuticals; and has received research support from Bristol-Myers Squibb/Sanofi-Synthelabo Partnership, Pfizer, Otsuka America Pharmaceuticals, and Eli Lilly. Dr Libby has been a consultant for AstraZeneca, Avant Immunotherapeutics, Bayer, Bristol-Myers Squibb, Cor- Key, Fournier, Interleukin Genetics, Merck, Millen- nium Pharmaceuticals, Novartis, Pfizer, Pierre Fabre, San- kyo, Sanofi, Schering Plough, and GlaxoSmithKline; has been on the speakers bureau for Bayer, Bristol-Myers Squibb, Merck, Novartis, and Pfizer; and has received research support from Bayer, Bristol-Myers Squibb, Fournier, Merck, Millennium Pharmaceuticals, Novar- tis, Pfizer, Sankyo, and GlaxoSmithKline. Corresponding Author and Reprints: Peter Libby, MD, 228 Longwood Ave, Suite 307, Boston, MA 02115 Context Complications of atherosclerosis cause most morbidity and mortality in pa- tients with diabetes mellitus. Despite the frequency and severity of disease, proven medical therapy remains incompletely un Continue reading >>
New Aspects In The Pathogenesis Of Diabetic Atherothrombosis - Sciencedirect
Volume 44, Issue 12 , 21 December 2004, Pages 2293-2300 New aspects in the pathogenesis of diabetic atherothrombosis Author links open overlay panel Pedro R.MorenoMD* Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atheroscl Continue reading >>
Get Unlimited Access On Medscape.
You’ve become the New York Times and the Wall Street Journal of medicine. A must-read every morning. ” 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 >>
Role Of Diabetes In Atherosclerotic Pathogenesis. What Have We Learned From Animal Models? - Em|consulte
Role of diabetes in atherosclerotic pathogenesis. What have we learned from animal models? Tirs part : Renard. CINSERM, Unit 145, Facult de Mdecine, avenue de Valombrose, 06107 Nice Cedex France. Rle du diabte dans la pathogense de l'athrosclrose. Qu'avons-nous appris des modles animaux? Le diabte est associ une augmentation du risque de dvelopper des lsions d'athrosclrose et leurs complications: accident vasculaire crbral, infarctus du myocarde et atteinte vasculaire priphrique. Chez les patients diabtiques, l'athrosclrose est une maladie complexe et multifactorielle. Les lsions s'aggravent plus rapidement et sont plus svres que dans la population non diabtique. Plusieurs facteurs de risque ont t proposs pour expliquer l'augmentation du risque de maladies cardiovasculaires avec le diabte. Ces facteurs de risque incluent: l'hyperglycmie, la dyslipidmie, la formation acclre des produits de la glycation avance (AGEs), l'augmentation du stress oxydatif et des facteurs gntiques. Les tudes pidmiologiques ne permettent pas, elle seules, de dterminer prcisment les facteurs de risque qui entranent l'acclration de l'athrosclrose, car tous ces facteurs coexistent chez les patients diabtiques. Des modles animaux reproduisant l'augmentation de l'athrosclrose sont donc prcieux pour comprendre pourquoi l'athrosclrose est acclre chez les diabtiques et pour laborer des traitements qui permettent de limiter sa progression. Cette revue analyse la plupart des modles animaux qui ont t dvelopps pour reproduire l'athrosclrose acclre par le diabte, et rsume les effets de l'hyperglycmie et des anomalies lipidiques sur l'athrogense. Diabetes mellitus is associated with a greater risk of developing atherosclerosis and its complications: stroke, myocardial infarction, and peripheral vascular dis Continue reading >>
