Diabetes And Vascular Disease: Pathophysiology, Clinical Consequences, And Medical Therapy: Part I
The number of people with diabetes mellitus is alarmingly increasing due to the growing prevalence of obesity, genetic susceptibility, urbanization, and ageing.1,2 Type 2 diabetes, the most common form of the disease, may remain undetected for many years and its diagnosis is often made incidentally through an abnormal blood or urine glucose test. Hence, physicians often face this disease at an advanced stage when vascular complications have already occurred in most of patients. Macrovascular complications are mainly represented by atherosclerotic disease and its sequelae. Diabetes-related microvascular disease such as retinopathy and nephropathy are major causes of blindness and renal insufficiency.1 Based on this scenario, a better understanding of the mechanisms underlying diabetic vascular disease is mandatory because it may provide novel approaches to prevent or delay the development of its complications. This review will focus on the most current advances in the pathophysiology of vascular disease (Part I) and will address clinical manifestations and management strategies of patients with diabetes (Part II). The alterations in vascular homeostasis due to endothelial and smooth muscle cell dysfunction are the main features of diabetic vasculopathy favouring a pro-inflammatory/thrombotic state which ultimately leads to atherothrombosis. Macro- and microvascular diabetic complications are mainly due to prolonged exposure to hyperglycemia clustering with other risk factors such as arterial hypertension, dyslipidemia as well as genetic susceptibility.3 Interestingly, nephropathy, retinopathy, and diabetic vascular disease are in line with the notion that endothelial, mesangial, and retinal cells are all equipped to handle high sugar levels when compared with other cell Continue reading >>
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What Is The Pathogenesis Of Atherosclerosis In Diabetic Ulcers?
What is the pathogenesis of atherosclerosis in diabetic ulcers? Overall, people with diabetes mellitus (DM) have a higher incidence of atherosclerosis , thickening of capillary basement membranes, arteriolar hyalinosis, and endothelial proliferation. Calcification and thickening of the arterial media (Mnckeberg sclerosis) are also noted with higher frequency in the diabetic population, although whether these factors have any impact on the circulatory status is unclear. Diabetic persons, like people who are not diabetic, may develop atherosclerotic disease of large-sized and medium-sized arteries, such as aortoiliac and femoropopliteal atherosclerosis. However, significant atherosclerotic disease of the infrapopliteal segments is particularly common in the diabetic population. Underlying digital artery disease, when compounded by an infected ulcer in close proximity, may result in complete loss of digital collaterals and precipitate gangrene. Amin N, Doupis J. Diabetic foot disease: From the evaluation of the "foot at risk" to the novel diabetic ulcer treatment modalities. World J Diabetes. 2016 Apr 10. 7 (7):153-64. [Medline] . [Full Text] . Naves CC. The Diabetic Foot: A Historical Overview and Gaps in Current Treatment. Adv Wound Care (New Rochelle). 2016 May 1. 5 (5):191-197. [Medline] . [Full Text] . Rice JB, Desai U, Cummings AK, Birnbaum HG, Skornicki M, Parsons NB. Burden of diabetic foot ulcers for Medicare and private insurers. Diabetes Care. 2014. 37 (3):651-8. [Medline] . Gentile AT, Berman SS, Reinke KR, Demas CP, Ihnat DH, Hughes JD, et al. A regional pedal ischemia scoring system for decision analysis in patients with heel ulceration. Am J Surg. 1998 Aug. 176(2):109-14. [Medline] . Beckert S, Witte M, Wicke C, Konigsrainer A, Coerper S. A new wound-based Continue reading >>
Pathogenesis Of Atherosclerosis In Diabetes And Hypertension
Pathogenesis of Atherosclerosis in Diabetes and Hypertension Get access/doi/pdf/10.3109/10641969909068650?needAccess=true Prevalence of atherosclerotic vascular disease is markedly increased among individuals with diabetes-mellitus and hypertension. Its major clinical manifestations are consequences of atherosclerosis of coronary arteries, cerebral arteries and large arteries of lower extremities. Thus, atherosclerotic vascular disease is the major cause of mortality and significant morbidity in diabetes and hypertension. Dyslipidemia, hyperinsulinemia. and central obesity seem to be associated with increased risk of atherosclerosis, along with the development of hypertension and diabetes (NIDDM). Insulin resistance is the fundamental factor in this situation which has strong genetic predisposition. Accelerated atherosclerosis in diabetes due to mechanism unique to diabetes like non-enzymatic glycation of proteins, oxidative modification of lipoproteins, formation of lipoproteins immune complexes, lipoproteins aggregation, disturbances of cell replication and growth factors and propensity to thrombosis are clearly established Therapeutic implication for the prevention of atherosclerosis in diabetes and hypertension clearly emphasizes the need to achieve tight control of gyperglycemia, hypertension, and hyperlipidemia in addition to avoiding cigarette smoking and developing obesity. Continue reading >>
- Conjoint Associations of Gestational Diabetes and Hypertension With Diabetes, Hypertension, and Cardiovascular Disease in Parents: A Retrospective Cohort Study
- Diet Soda Intake and Risk of Incident Metabolic Syndrome and Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)*
- How Does Diabetes Cause Atherosclerosis?
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 >>
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 >>
Atherosclerosis | Pathology | Britannica.com
Alternative Title: intimal arteriosclerosis Atherosclerosis, chronic disease caused by the deposition of fats, cholesterol , calcium, and other substances in the innermost layer of endothelium of the large and medium-sized arteries. Atherosclerosis is the most common arterial abnormality characterized as arteriosclerosis , which is defined by the loss of arterial elasticity due to vessel thickening and stiffening. The precise mechanisms of atherosclerosis are not completely understood, but there is evidence that in some people the condition can begin in childhood with the formation of tiny fatty streaks, or streaks of fat deposition, in the arteries. As the endothelium is infiltrated by more and more fatty materialsprimarily low-density lipoproteins (LDLs), protein-lipid complexes that serve as a vehicle for delivering cholesterol to the bodyimmune cells called macrophages are drawn to the site to scavenge the materials. When filled with lipids the macrophages become known as foam cells, which later die and accumulate in the endothelial lining. Other materials are also deposited in the lining, including salts of calcium and other minerals, smooth muscle cells, and cellular debris of varying composition . This causes the initially tiny lesions to enlarge and thicken to form atheromas, or atherosclerotic plaques . These plaques may narrow the vessel channel, interfering with the flow of blood. Endothelial injury, either as a result of lipid deposition or as a result of another cause, may also be accompanied by the formation of fibrous caps of scar tissue. These areas of scar tissue make the vessel walls less elastic, with one consequence being an increase in blood pressure . Thick plaques that severely occlude an artery can significantly decrease the flow of blood to vas Continue reading >>
The Pathogenesis Of Arteriosclerosis And Diabetes Mellitus
The Pathogenesis of Arteriosclerosis and Diabetes Mellitus Part of the Verhandlungen der Deutschen Gesellschaft fr Innere Medizin book series (VDGINNERE, volume 93) Of the major risk factors for atherosclerosis in the general population, most affect diabetics of both types, particularly high levels of triglyceride-rich lipoproteins, low levels of high density lipoproteins, and hyperinsulinemia. The three major features of atherosclerosis, i.e., lipid accumulation, within the arterial intima (smooth muscle cell proliferation and macrophage recruitment) and connective tissue deposition, all may be influenced by the diabetic State. In the reaction to injury hypothesis, endothelial injury (functional or gross) appears to be the initial Step. This is associated with adherence of circulating monocytes, which then migrate across the endothelium to the intima where they become macrophages and accumulate cholesterol (foam cells). Smooth muscle cells are stimulated to migrate and proliferate into the intima, leading to further foam cell formation. Loss of endothelial integrity is followed by the adherence of platelets to the exposed subendothelial connective tissue. A potent mitogen released from platelets (platelet-derived growth factor (PDGF)) stimulates further smooth-muscle cell proliferation and synthesis of connective tissue matrix associated with the transformation of a fatty streak to a fibrous plaque. The diabetic state could potentially influence many of the events involved in the pathogenesis of atherosclerosis. A primary genetic defect in diabetes associated with impaired replication of all cells could reduce endothelial repair. High glucose concentrations have also been shown to inhibit endothelial cell division. High concentrations of triglyceride-rich lipoproteins 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 >>
Diabetes And Atherosclerosis: Is There A Role For Hyperglycemia?
Abstract Atherosclerosis is accelerated in both type 1 and type 2 diabetes. The hallmark of diabetes is the presence of hyperglycemia. In this article, we review the role of glucose in the pathogenesis of atherosclerosis. Evidence obtained from epidemiological, in vitro, and animal studies will be reviewed in an attempt to understand the complex relationship between hyperglycemia and cardiovascular risk that is emerging from clinical trials. EPIDEMIOLOGICAL EVIDENCE SUPPORTS AN ASSOCIATION BETWEEN GLYCEMIC CONTROL AND CARDIOVASCULAR DISEASE Strong epidemiological evidence supports an association between glycemic control and CVD risk (4). The United Kingdom Prospective Diabetes Study (UKPDS) provided additional insights into the relationship between glycemic control and CVD in patients with type 2 diabetes, indicating a linear relationship between HbA1c and CVD endpoints, particularly myocardial infarction (5). However, the slope of the relationship between HbA1c and microvascular complications is much steeper that than for myocardial infarction, raising the question of whether glucose plays a greater role in the pathogenesis of microvascular than cardiovascular complications of diabetes. Similar but less-robust relationships have been observed in patients with type 1 diabetes (6). However, epidemiological studies only indicate associations, and provide no evidence of causality. Therefore, other approaches are necessary to understand the potential role of hyperglycemia in the pathogenesis of cardiovascular disease. 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 potenti 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 >>
- Diet Soda Intake and Risk of Incident Metabolic Syndrome and Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)*
- Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose in Type 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study
- 8 Valuable Life-Saving Lessons I Learned from My Dad’s Type 1 Diabetes
Atherosclerosis Knowledge For Medical Students And Physicians
Atherosclerosis is the most common type of arteriosclerosis , or thickening and stiffening of the arterial wall. Major risk factors include smoking, diabetes mellitus , arterial hypertension , dyslipidemia , family history of early heart disease, and advanced age. The pathogenesis is a complicated process precipitated by endothelial damage, which leads to an invasion of inflammatory cells into the tunica intima and adhesion of platelets to the disrupted endothelium. Invading smooth muscle cells (SMCs) and macrophages take up cholesterol from oxidized low-density lipoprotein (LDL) in the vessel wall. They then become foam cells , which accumulate in early atherosclerotic lesions ( fatty streaks ), triggering the production of extracellular matrix (e.g., collagen). This leads to the formation of fibrous plaques (from cells, extracellular matrix, free cholesterol, and cellular debris), which may rupture and lead to thrombosis. Common sites of atherosclerosis include the abdominal aorta , coronary arteries, popliteal arteries, and carotid arteries. Depending on the location, atherosclerosis may lead to a variety of conditions, such as arterial aneurysms , dissection , coronary heart disease (CHD), peripheral artery disease ( PAD ), intestinal ischemia , subcortical vascular dementia ( Binswanger's disease ), thrombosis (e.g., acute coronary syndrome and stroke ), and renovascular hypertension . Arteriosclerosis : arterial wall thickening and elasticity loss with variable pathogenesis Atherosclerosis (most common type of arteriosclerosis ): multifactorial inflammatory disease of the intima, manifesting at points of hemodynamic shear stress Mnckeberg's arteriosclerosis : dystrophic calcification of the media Arteriolosclerosis: hardening of arterioles Medical treatment: Trea 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 >>
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Pathogenesis Of Atherosclerosis In Diabetes Mellitus.
Abstract Numerous studies have shown that patients with diabetes mellitus have accelerated atherosclerotic vascular disease, and major advances in understanding it pathogenesis have been made. Current suggestions are that endothelial injury may be the initial event in the genesis of atherosclerosis, followed by platelet adhesion and aggregation at the site of injury. In diabetes, evidence of endothelial dysfunction is present. Smooth muscle cell proliferation is an important pathologic finding in atherosclerosis. This process is stimulated by a platelet mitogen, which has been partially characterized. The mitogen has not been studied in diabetes. Lipid accumulation in the area of the atherosclerotic lesion is primarily in the form of intracellular and extracellular esterified cholesterol. In uncontrolled diabetes, elevated plasma low density lipoprotein levels and decreased plasma high density lipoprotein levels favor lipid deposition in large vessels. There is evidence of a thrombotic state in certain diabetic patients. Collectively, these abnormalities of endothelial, platelet, smooth muscle, lipoprotein, and coagulation behavior may be viewed as contributing to the problem of accelerated atherosclerosis in diabetes. A thorough understanding of the pathogenesis of this process aids in designing appropriate preventive therapeutic approaches. Continue reading >>
New Concepts About The Pathogenesis Of Atherosclerosis In Diabetes Mellitus.
New concepts about the pathogenesis of atherosclerosis in diabetes mellitus. Colwell JA , Winocour PD , Lopes-Virella M , Halushka PV . New concepts about the pathogenesis of atherosclerosis in diabetes mellitus are presented. Emphasis is given to alterations of endothelial function, as indicated by von Willebrand factor activity, prostacyclin release, and fibrinolytic activity in diabetes mellitus. Previous work on platelet aggregation and arachidonic acid metabolism is updated and recent findings are emphasized. The atherogenic mix of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels in uncontrolled diabetes mellitus is noted. The lipid hypothesis is extended by consideration of very low-density lipoprotein and intermediate-density lipoprotein metabolism in diabetes. Lipoprotein-cell interactions that may contribute to atherosclerosis are reviewed and suggestions are made for future research in order to clarify the pathogenesis of atherosclerosis in diabetes mellitus. Continue reading >>