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Diabetic Microangiopathy Pathogenesis

Do Genetic Factors Play A Role In The Pathogenesis Of Diabetic Microangiopathy?

Do Genetic Factors Play A Role In The Pathogenesis Of Diabetic Microangiopathy?

, Volume 27, Issue5 , pp 487492 | Cite as Do genetic factors play a role in the pathogenesis of diabetic microangiopathy? There is no direct and conclusive evidence that genetic factors play a role in the pathogenesis of microangiopathy in diabetes. Associations between HLA antigens and complications, which would contribute conclusive evidence of a genetic contribution to the genesis of these complications, have been reported but not consistently confirmed. On the other hand, circumstantial evidence from studies of the natural history of the disease and its complications and from twin studies strongly suggest that genes do contribute to the susceptibility to small vessel disease. The most important genes providing this susceptibility are probably unrelated to HLA. Even if the total genetic contribution to susceptibility for microangiopathy turns out to be small in comparison with that provided by metabolic factors, their knowledge early in the course of the disease would serve the important role of identifying subjects in need of more intensive diabetic management to prevent vascular complications. Public HealthInternal MedicineNatural HistoryHuman PhysiologyMetabolic Disease These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. Ross H, Rifkin H (1980) Metabolic control and vascular disease in diabetes mellitus. In: Podolsky S (ed) Clinical diabetes: modern management. Appleton-Century-Crofts, New York, pp 565588 Google Scholar Barbosa J (1980) Nature and nurture: the genetics of diabetic microangiopathy. In: Podolsky S, Viswanathan M (eds) Secondary diabetes: the spectrum of diabetic syndromes. Raven Press, New York, pp 6775 Google Scholar Kohner EM, McLeod D, Marsh Continue reading >>

Role And Limits Of Glycemic Regulation In The Pathogenesis Of Diabetic Microangiopathy

Role And Limits Of Glycemic Regulation In The Pathogenesis Of Diabetic Microangiopathy

Role and limits of glycemic regulation in the pathogenesis of diabetic microangiopathy Authors: Le Dvhat, C. ; | Khodabandehlou, T. | Zhao, H. ; | Vimeux, M. Affiliations: Service DiabtologieEndocrinologieNutrition, Centre Hospitalier, 58000 Nevers, France | Unit de Recherches dHmorhologie Clinique, Centre Hospitalier, 58000 Nevers, France | Research Institute, ChinaJapan Friendship Hospital, Beijing, China Abstract: The relationship between either an acute or a chronic hyperglycemia and functional microcirculatory disturbances was studied in insulindependent diabetic (IDD) patients in comparison to healthy volunteers. Acute hyperglycemia, provoked in 10 IDD patients, was accompanied by an increase in laser doppler skin blood flux while transcutaneous oxygen pressure (TcPO_2) decreased. These changes, accompanied by that in the concentration of moving blood cells indicate that acute hyperglycemia results in a vasodilation in favour of nonnutritive microvascular shunts. The effect of chronic hyperglycemia was studied in 36 IDD patients who had a duration of diabetes of less than 5 years and had no clinical signs of micro and macroangiopathy. In these patients, erythrocyte aggregation, plasma viscosity and fibrinogen concentration were increased and transcutaneous oxygen pressure reduced, compared with the levels seen in healthy subjects. More marked impairments were observed in patients with poor glycemic control. This suggests that chronic hyperglycemia involves functional disturbances which will contribute to the development of the vascular complications of diabetes. In 34 patients with poorly controlled diabetes who received intensive insulin therapy for 36 months, these changes were reversed in patients in whom good glycemic control was achieved within 2 months, but Continue reading >>

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Pathogenesis Of Diabetic Macro- And Microangiopathy.

Pathogenesis Of Diabetic Macro- And Microangiopathy.

Pathogenesis of diabetic macro- and microangiopathy. Department of Pathology, Eberhard Karls University Tbingen, Germany. [email protected] Epidemiological investigations reveal that we must expect a rapid increase in cases of diabetes mellitus in the next few years. As a result, vascular complications in the form of macro- and microangiopathy are also expected to arise more frequently. A classical example of macroangiopathy is coronary arteriosclerosis, microangiopathy is exemplified by diabetic nephropathy. In patients suffering from diabetes, macroangiopathy manifests as atherosclerosis like in nondiabetic patients, characterized by formation of plaques that follows in stages but with an accelerated course due to the different risk factors, especially hyper- and dyslipidemia, with cumulative effects. Thus, atherosclerosis in diabetes begins earlier, is more markedly pronounced and progresses more rapidly. The pathogenetic concept is based on an endothelial lesion that occurs as a result of a diabetes-specific, endothelium-damaging parameters. In case of diabetic microangiopathy histologically characterized by a progressive glomerulosclerosis, arteriolosclerosis and interstitial fibrosis hyperglycemia, along with its consecutive and complex processes that induce matrix increase, is considered to be the primary pathogenetically relevant factor involved. Insulin resistance seems to be the major common denominator at the center of both diabetic macroangiopathy and microangiopathy. Continue reading >>

Diabetic Retinopathy And Endothelin System: Microangiopathy Versus Endothelial Dysfunction

Diabetic Retinopathy And Endothelin System: Microangiopathy Versus Endothelial Dysfunction

Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications. Diabetic retinopathy (D Continue reading >>

Diabetes And Diabetic Complications

Diabetes And Diabetic Complications

The Maillard reaction and diabetes mellitus (Contribution from Dr Alejandro Gugliucci MD, PhD) Diabetes mellitus, a condition characterized mainly by a quantitative deficiency in insulin secretion or a resistance to insulin action, is estimated to afflict 8% of the population. This creates a huge economic burden related for the most part to the management of its complications, which are micro and macroangiopathic in nature. Microangiopathy, the microvessel disease in diabetes, includes retinopathy, nephropathy, and neuropathy and in type 1 patients the first signs of these complications may develop even in adolescence, particularly if insulin treatment has been inadequate. Similar complications occur later in life in type 2 patients and are frequently present at the time of diagnosis. The precise mechanisms by which diabetic microangiopathy develops are not fully understood, but a consensus is emerging pointing to a terrain of genetic influences onto which metabolic and hemodynamic derangements are superimposed. The anatomic hallmark of diabetic microangiopathy is the thickening of capillary basement membranes, which subsequently induces occlusive angiopathy, tissue hypoxia, and damage. The evolution of the numerous long-term complications of diabetes mellitus correlates well, in most cases, with the severity and duration of hyperglycemia. It is known that, for instance, postprandial glucose levels above 200 mg/dL (11 mM) are more frequently associated with renal, retinal, and neurologic complications that can commence 5 to 10 years after the debut of the disease. It is noteworthy to point out here that, at the time of initial diagnosis of type 2 diabetes, many patients have postprandial glucose levels above 200 mg/dL and already display some degree of diabetic complica Continue reading >>

Pathogenesis Of Diabetic Microangiopathy. The Hemodynamic View

Pathogenesis Of Diabetic Microangiopathy. The Hemodynamic View

Pathogenesis of diabetic microangiopathy. The hemodynamic view Pathogenesis of diabetic microangiopathy. The hemodynamic view Pathogenesis of Diabetic Microangiopathy The Hemodynamic ViewROBERTO ZATZ, M.D. BARRY M. BRENNER, M.D. Boston,MassachusettsFrom the Departments ... Key Concepts in A Modern View of Alzheimer's Pathogenesis Recent research has prompted a welcome evolution of theory in Alzheimer's disease. Old and simplistic concepts are Pathogenesis of Diabetic Microangiopathy The Hemodynamic View ROBERTO ZATZ, M.D. BARRY M. BRENNER, M.D. Boston, From the Departments of Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston, Massachusetts. Requests for reprints should be addressed to Dr. Barry M. Brenner, Renal Division, Brigham and Womens Hospital, 75 Francis Street, Boston, Massachusetts 02115. Manuscript accepted June 4, 1985. Multiple factors, including altered levels of vasoactive substances, altered vasomotor responsiveness, chronic plasma volume expansion, and tissue hypoxia, contribute to a state of generalized microvascular vasodilatation in early insulin-dependent diabetes mellitus. This vasodilatation, with the consequent elevation in capillary pressures and flows, may be the initiating mechanism leading to both renal and extrarenal diabetic microangiopathy. Sustained hemodynamic actions on the microvasculature, besides directly injuring the capillary wall, promote increased permeability to macromolecules and increased capillary wall proliferation, with consequent thickening of basement membranes and luminal narrowing. These changes eventuate in complete microvascular obstruction and further vasodilatation of less damaged capillaries, thereby ensuring their eventual destruction. The ensuing complications depend on the nature of the su Continue reading >>

Review Article Diabetic Microangiopathy A Current Look At The Pathogenesis And The Clinical Implications For Cardiovascular Diseases

Review Article Diabetic Microangiopathy A Current Look At The Pathogenesis And The Clinical Implications For Cardiovascular Diseases

Papers, Reference Manager, RefWorks, Zotero Szmit S, Opolski G. Review articleDiabetic microangiopathy a current look at the pathogenesis and the clinical implications for cardiovascular diseases. Przegld Kardiodiabetologiczny/Cardio-Diabetological Review. 2007;1(1):27-34. Szmit, S., & Opolski, G. (2007). Review articleDiabetic microangiopathy a current look at the pathogenesis and the clinical implications for cardiovascular diseases. Przegld Kardiodiabetologiczny/Cardio-Diabetological Review, 1(1), 27-34. Szmit, Sebastian, and Grzegorz Opolski. 2007. "Review articleDiabetic microangiopathy a current look at the pathogenesis and the clinical implications for cardiovascular diseases". Przegld Kardiodiabetologiczny/Cardio-Diabetological Review 1 (1): 27-34. Szmit, S., and Opolski, G. (2007). Review articleDiabetic microangiopathy a current look at the pathogenesis and the clinical implications for cardiovascular diseases. Przegld Kardiodiabetologiczny/Cardio-Diabetological Review, 1(1), pp.27-34. Szmit, Sebastian et al. "Review articleDiabetic microangiopathy a current look at the pathogenesis and the clinical implications for cardiovascular diseases." Przegld Kardiodiabetologiczny/Cardio-Diabetological Review, vol. 1, no. 1, 2007, pp. 27-34. Szmit S, Opolski G. Review articleDiabetic microangiopathy a current look at the pathogenesis and the clinical implications for cardiovascular diseases. Przegld Kardiodiabetologiczny/Cardio-Diabetological Review. 2007;1(1):27-34. Microangiopathy is one of the chronic complications in patients with diabetes mellitus. Morphological and functional changes in vessels below 100 nm are typical for diabetic microangiopathy. There are many genetic, biochemical and haemodynamic factors causing microangiopathy. The most important clinical ch Continue reading >>

[pathogenesis Of Diabetic Microangiopathy. Fluoroangioretinal Observations During Monocomponent... - Abstract - Europe Pmc

[pathogenesis Of Diabetic Microangiopathy. Fluoroangioretinal Observations During Monocomponent... - Abstract - Europe Pmc

Type: English Abstract, Journal Article(lang: ita) Current theories on the pathogenesis of diabetic microangiopathy and their effective therapeutical implications are reviewed. The possible role of insulin antibody production in insulin-treated diabetics concerning development and progression of retinopathy is particularly discussed. Thus the opportunity of a monocomponent (MC) insulin treatment in all newly diagnosed insulin-dependent diabetics is considered. The authors have carried out fluorescein angiography in two groups of subjects with JOD comparable for age, sex, diabetes duration (5-7 years), insulin requirement, metabolic control, absence of diabetic heredity as well as of clinical (ophtalmoscopic) signs of microangiopathy (retinopathy). The first group had been treated from the beginning with MC porcine insulin (Monotard) only; the second one with conventional Lente only. Early fluoroangiographic signs of retinopathy ("pre-retinopathy") as increased capillary filling, ischaemic areas, alterations in capillary permeability, microangioaneurysms, "primary exudation" had to be detected. In 2 out of 10 cases in the first group one isolated sign was found; one or more signs were found in the second group. In the first group the insulin antibody titer (IB) was under or nearly above the detection limit; in the second group insulin antibody titer was significantly positive. These preliminary findings suggest a larger prospective study. Continue reading >>

Pathogenesis Of Diabetic Microangiopathy. The Hemodynamic View.

Pathogenesis Of Diabetic Microangiopathy. The Hemodynamic View.

Pathogenesis of diabetic microangiopathy. The hemodynamic view. Multiple factors, including altered levels of vasoactive substances, altered vasomotor responsiveness, chronic plasma volume expansion, and tissue hypoxia, contribute to a state of generalized microvascular vasodilatation in early insulin-dependent diabetes mellitus. This vasodilatation, with the consequent elevation in capillary pressures and flows, may be the initiating mechanism leading to both renal and extrarenal diabetic microangiopathy. Sustained hemodynamic actions on the microvasculature, besides directly injuring the capillary wall, promote increased permeability to macromolecules and increased capillary wall proliferation, with consequent thickening of basement membranes and luminal narrowing. These changes eventuate in complete microvascular obstruction and further vasodilatation of less damaged capillaries, thereby ensuring their eventual destruction. The ensuing complications depend on the nature of the surrounding tissue, ranging from reduction of functional reserve, as seen in skeletal muscle, to the devastating functional consequences observed in organs with endarterial circulation such as the kidney and retina. Continue reading >>

An Insight In To The Pathogenesis Of Diabetic Vascular Diseases: Role Ofoxidative Stress And Antioxidants

An Insight In To The Pathogenesis Of Diabetic Vascular Diseases: Role Ofoxidative Stress And Antioxidants

Received date: October 18, 2013; Accepted date: November 25, 2013; Published date: November 27, 2013 Citation: Aditi, Mahajan N, Rawal S, Katare R (2013) An Insight in to the Pathogenesis of Diabetic Vascular Diseases: Role of Oxidative Stress and Antioxidants. Pharmaceut Anal Acta 4:273. doi: 10.4172/2153-2435.1000273 Copyright: 2013 Aditi, 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. The profound effects of hyperglycaemia on the vascular tree are the major causes of morbidity and mortality among patients suffering from diabetes. Diabetic Vascular Diseases (DVD) includes accelerated forms of atherosclerosis due to endothelial dysfunction and microangiopathy of retinal vessels. A host of several studies indicate that increased oxidative stress play a pivotal role in the development and progression of diabetic vascular diseases. The metabolic abnormalities due to oxidative stress are linked to the structural and functional changes in the vasculature, consequently resulting in atherosclerosis and diabetic retinopathy. Oxidative stress brings alterations in downstream transcription factors which result in changes in gene expression, myocardial substrate utilization, myocyte growth, endothelial function and myocardial compliance. Based on this, an approach towards investigating new and effective antioxidant therapies could serve as potential therapeutic implications in preventing the deleterious effects of oxidative stress on vasculature. This review aims to understand the underlying mechanisms involved in the pathogenesis of vascular complications in diabetes with special empha Continue reading >>

Endothelial Dysfunction And Pathogenesis Of Diabetic Angiopathy

Endothelial Dysfunction And Pathogenesis Of Diabetic Angiopathy

Endothelial dysfunction and pathogenesis of diabetic angiopathy aDepartment of Internal Medicine, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands bInstitute for Cardiovascular Research, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands Corresponding author. Tel. +31 20 4440531; Fax +31 20 4440502. Search for other works by this author on: aDepartment of Internal Medicine, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands bInstitute for Cardiovascular Research, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands Search for other works by this author on: aDepartment of Internal Medicine, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands bInstitute for Cardiovascular Research, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands Search for other works by this author on: cGaubius Laboratory, TNO Prevention and Health, 2301 CE Leiden, Netherlands Search for other works by this author on: Cardiovascular Research, Volume 34, Issue 1, 1 April 1997, Pages 5568, Coen D.A Stehouwer, Jan Lambert, A.J.M Donker, Victor W.M van Hinsbergh; Endothelial dysfunction and pathogenesis of diabetic angiopathy, Cardiovascular Research, Volume 34, Issue 1, 1 April 1997, Pages 5568, Objective and Methods: To review, from the clinical perspective, the contribution of dysfunction of the vascular endothelium to the pathogenesis of diabetic micro- and macroangiopathy. Results: Available data indicate that endothelial dysfunction in diabetes complicated by micro- or macroalbuminuria (renal microangiopathy) is generalised. The close linkage between microalbuminuria and endothelial dysfunction is an attractive explanation for the fact that microalbumi Continue reading >>

Pathogenesis Of Diabetic Microangiopathy. The Hemodynamic View

Pathogenesis Of Diabetic Microangiopathy. The Hemodynamic View

Volume 80, Issue 3 , March 1986, Pages 443-453 Pathogenesis of diabetic microangiopathy. The hemodynamic view Author links open overlay panel RobertoZatzM.D. Barry M.BrennerM.D. Get rights and content Multiple factors, including altered levels of vasoactive substances, altered vasomotor responsiveness, chronic plasma volume expansion, and tissue hypoxia, contribute to a state of generalized microvascular vasodilatation in early insulin-dependent diabetes mellitus. This vasodilatation, with the consequent elevation in capillary pressures and flows, may be the initiating mechanism leading to both renal and extrarenal diabetic microangiopathy. Sustained hemodynamic actions on the microvasculature, besides directly injuring the capillary wall, promote increased permeability to macromolecules and increased capillary wall proliferation, with consequent thickening of basement membranes and luminal narrowing. These changes eventuate in complete microvascular obstruction and further vasodilatation of less damaged capillaries, thereby ensuring their eventual destruction. The ensuing complications depend on the nature of the surrounding tissue, ranging from reduction of functional reserve, as seen in skeletal muscle, to the devastating functional consequences observed in organs with endarterial circulation such as the kidney and retina. Continue reading >>

Payperview: Does Microangiopathy Contribute To The Pathogenesis Of The Diabetic Foot Syndrome? - Karger Publishers

Payperview: Does Microangiopathy Contribute To The Pathogenesis Of The Diabetic Foot Syndrome? - Karger Publishers

Does Microangiopathy Contribute to the Pathogenesis of the Diabetic Foot Syndrome? Coppelli A. Abbruzzese L. Goretti C. Iacopi E. Riitano N. Piaggesi A. Department of Medicine, University of Pisa I have read the Karger Terms and Conditions and agree. Chronic diabetic complications, both micro and macrovascular, have become a serious issue worldwide, and the dramatic rise in the number of patients with diabetes has exacerbated the problem. Hyperglycemia represents the pathologic hallmark of diabetes mellitus and induces vascular damages probably through a common pathway represented by increased intracellular oxidative stress. Among diabetic chronic complications, the pathology related to diabetic foot plays a major role and is the most common reason for hospitalization in diabetic patients. Nearly all components of the lower extremity are involved in the pathological process: skin, subcutaneous cellular tissue, muscles, bones, joints, vessels, nerves. Despite the role of microangiopathic complications in diabetic patients (retinopathy, nephropathy and neuropathy affect most both type 1 and type 2 diabetic patients), the relevance of small vessels damage in the pathogenesis and clinical history of diabetic foot syndrome remains elusive and is still debated. For several years, microangiopathy has not been considered an important pathogenic factor in the development of a diabetic foot ulcer. However, several functional and structural microvascular changes can be detected at the microvascular level in diabetic patients, which might increase the vulnerability of the skin or which can contribute to impaired wound healing. In this review, we highlighted some most exploited pathways involved in the pathogenesis of microangiopathy. We also emphasized the emerging role of microan Continue reading >>

Diabetic Skin Microangiopathy : Studies On Pathogenesis And Treatment

Diabetic Skin Microangiopathy : Studies On Pathogenesis And Treatment

Diabetic skin microangiopathy : Studies on pathogenesis and treatment Location: Thoraxklinikens aula, Karolinska Sjukhuset Department: Institutionen fr medicin / Department of Medicine Background: Most of late diabetic complications have their basis in adisturbed microcirculation, i.e. diabetic microangiopathy. This alongwith peripheral arterial occlusive disease (PAOD) and neuropathycontribute to the development of chronic diabetic foot ulcers, a severeand expensive complication often leading to lower-limb amputations and anincreased death rate. Hypercoagulation and impaired fibrinolysisassociated with diabetes mellitus might contribute to the pathogenesis ofdiabetic microangiopathy.Aims: 1. To study the effects of the low molecular weight heparincompound dalteparin (Fragmin, Pharmacia Corporation/Pfizer) on a) ulceroutcome, b) peripheral macro- and microcirculation, and c) haemostaticfunction, in patients with diabetes, PAOD and chronic foot ulcers.2. To evaluate the predictive values of macro- (toe blood pressure, TBP)and microcirculatory (transcutaneous oxygen tension, TcP02) measurementsfor ulcer outcome in patients with diabetes.Methods: 1. Prospective, randomised, double-blind and placebo-controlledmulticenter study. The patients were randomised to treatment with dailyinjections of 5000 U dalteparin or placebo, until ulcer healing or for amaximum of six months. Ulcer healing was evaluated every fourth week, andperipheral circulation and haemostatic function at baseline, after 3 and6 months, or earlier in case of discontinuation of treatment. Foot skinmicrocirculation was evaluated by TcP02 and laser Doppler fluxmetry(LDF), and haemostatic function by analysis of plasma fibrinogenconcentration, fibrin gel structure (permeability coefficient, Ks; fibermass/length Continue reading >>

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