糖尿病肾血管病变及其发病机理

糖尿病的血管病变广泛存在，可累积供应机体各脏器的血管，它既可影响大血管，也可影响微血管。糖尿病的肾血管病变包括大血管病变如肾动脉硬化、肾小动脉硬化和引起糖尿病肾小球硬化症的微血管病变，现将其主要的病理改变和发病机制综述如下。糖尿病肾血管病变的病理改变[1,2]     

糖尿病与微循环

早已证实,糖尿病微血管病变及微循环障碍是糖尿病患者多种并发症的病理基础。糖尿病合并足坏疽的病因除大血管病变外,微血管病变及微循环障碍是导致糖尿病足坏疽发生、发展的重要原因之一。因此．糖尿病病人检测微循环,了解微循环的障碍程度．及时给予活血化瘀治疗对疾病的控制有重要意义。     

糖尿病微血管病变的分子学研究进展

糖尿病是一组全身性的内分泌代谢性疾病,其慢性并发症几乎涉及到全身各器官组织。微血管病变作为糖尿病的特征性并发症,是多种器官损害的病理生理基础,其主要改变为毛细血管基底膜增厚,微血管屏障功能破坏及进行性闭塞,组织缺氧。早期糖尿病以相关组织中微血管血流量增加和由此引起的血压增高为特点。微血管内皮细胞压力增加,引起更多的细胞外基质蛋白产生,其作为一种损伤性反应,必然引起微血管硬化症。糖尿病微血管改变主要引起糖尿病视网膜病变(DR)、糖尿病肾病(DN)、糖尿病心肌病变等。现将近几年糖尿病微血管病变的分子学研究进展作一综述。     

微血管内皮细胞功能改变与糖尿病微血管病变研究热点

糖尿病微血管病变是糖尿病多种并发症的病理基础,也是糖尿病预后的决定性因素,主要包括糖尿病视网膜病、糖尿病肾病、糖尿病神经病变及糖尿病心肌病变等。目前研究的热点主要涉及两方面,即糖基化终产物及其信号通路在糖尿病病变发生中的作用、微血管内皮细胞的功能改变与糖尿病血管病变的发生。本文就上述两方面的研究进展作一综述,并介绍本研究室的相关研究结果。     

缺氧诱导因子1α在糖尿病心肌病微血管病变中的作用机制

缺氧诱导因子1α(HIF-1α)是一种核转录调节因子,通过其下游基因的调控,参与糖尿病微血管并发症的发生与发展,对微血管的生成起关键作用.糖尿痛心肌病作为一种独立性疾病,其主要病理基础包括心肌微血管病变.HIF-1α可通过调控下游多种促血管新生因子,改善糖尿病心肌微血管病变、促进微血管生成,对改善心肌缺血、缺氧,延缓糖尿病心肌病的发生与发展起重要作用.HIF-1α对糖尿病心肌病的防治有潜在的临床意义.     

糖尿病性心脏病的临床特点和护理体会

目前威胁糖尿病病人生命最危险的病理为心血管病变，约70％以上的病人死于心血管病的各种并发症。心血管病变基本病理为动脉粥样硬化及微血管病变，糖尿病对心脏的影响包括大血管病变，微血管病变以及自主神经病变，称为糖尿病性心脏病。糖尿病性心脏病是一种慢性病变过程，也是糖尿病晚期主要死亡原因之一。2006年12月至2007年6月，我院内分泌科共收治糖尿病性心脏病患者23例，经正确治疗及积极有效的护理，取得良好效果，现将临床观察及护理体会总结如下。     

糖尿病与肺部疾病的关系

糖尿病是一种并发多器官病变的疾病,肾脏、视网膜、神经系统、微血管以及心血管系统均可受累,特别是糖尿病微血管病变也会累及肺泡一毛细血管网,从而对肺部产生影响,部分学者认为肺脏是糖尿病的靶向器官。本文就糖尿病对肺部的生理病理基础影响、肺功能的损害以及与肺部常见疾病的关系等方面进行综合阐述和分析。     

糖尿病微血管病变及治疗药物的研究进展

正糖尿病微血管病变常常伴有微循环障碍问题,在全身各处都可以见到。如何预防和延缓糖尿病微血管病变的发生以及发展尤为重要。下面就近年来关于微血管病变以及它的治疗药物的研究进展予以概述。1基本病理及发病机制(1)基本病理特征,基底膜变厚,红细胞聚集,内皮有所损伤,血液的粘稠度增高,血小板聚集和粘附,微血栓的形成,这些基本构成了微血管病变的主要过程。共同的病理学上的基础是微血管的结构功能发生改变,而且周细胞的丢失可能是微血管病变前期     

糖尿病微血管病变的发病机理

糖尿病微血管病变是决定糖尿病预后的主要因素,是糖尿病并发器官损害的病理基础。因此,研究微血管病变的发病机理,探讨预防和治疗措施是延长病人寿命,维护其正常活动能力的重要课题。微血管一般指介于微小动脉和微小静脉之间管腔直径在100微米以下的毛细血管网,它是血液与组织之间进行物质交换的场所。糖尿病微血管病变的发生是多种因素参与的,其主要特征是基底膜增厚。近年来不少学者还发现糖尿病人有微循环异常。血管壁病变与微循环异常互相影响,加上组织缺氧就使微血管病变日趋严重。     

糖尿病微血管病相关蛋白的研究进展

糖尿病微血管病是多因素协同作用导致的糖尿病常见慢性并发症，单纯纠正高血糖不能完全预防糖尿病微血管病变发生和阻止其发展进程，针对病理机制进行干预和治疗是必要的。本文对已发现与糖尿病微血管病发生和发展相关的多种蛋白进行综述，为筛选糖尿病微血管病的早期诊断和病因治疗靶向因子提供基础。     

Development of postpartum Graves’ disease and type 1 diabetes after delivery in a patient with gestational diabetes

Pregnancy and the postpartum period are associated with changes of the immune system. These changes might eventually result in autoimmune diseases, such as Graves’ disease and type 1 diabetes mellitus, in the postpartum period. We describe a case of a patient with gestational diabetes who developed both Graves’ disease and type 1 diabetes mellitus in the postpartum period. The pathology of gestational diabetes (GDM) is close to that of type 2 diabetes mellitus. However, the present case emphasizes the importance of screening and monitoring high‐risk GDM patients for all available autoimmune antibodies throughout pregnancy and the postpartum period, as GDM has a risk of developing into type 1 diabetes and multiple autoimmune diseases. In addition, only Graves’ disease was transient, whereas type 1 diabetes mellitus remained permanent in the present case. Thus, the present case shows etiological differences between these two autoimmune diseases. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00089.x,2011)     

Trends in mortality rates for death-certificate-coded diabetes mellitus in an English population 1979-99.

AIMS: Mortality statistics have customarily been coded and analysed using only one underlying cause of death. Rules for selecting the underlying cause, when more than one cause is certified on a death certificate, have changed twice in England over the past 20 years. We used data from death certificates for 1979-99 to compare mortality rates for diabetes mellitus certified anywhere on death certificates with those certified as the underlying cause. METHODS: Analysis of data from 18,917 death certificates that included diabetes mellitus in the former Oxford health region. RESULTS: Based on the underlying cause of death, mortality rates for diabetes varied substantially between the periods defined by rule changes. Based on mentions of diabetes anywhere on the death record, mortality rates were almost unchanged over time: they showed a non-significant rise of 0.1% per year (95% confidence interval -0.3, 0.6). Circulatory diseases were certified causes of death in 71% of all deaths in people with diabetes. Although mortality rates from circulatory diseases in the general population fell by 2.5% per year, rates for circulatory diseases in combination with diabetes did not fall. CONCLUSIONS: Two explanations are possible for the lack of change in mortality rates for diabetes based on all certified mentions between 1979 and 1999. Increasing prevalence and improved survival may have resulted in no net change; and/or there may have been no improvement in survival for people whose diabetes is associated with life-threatening pathology and in particular with circulatory diseases.     

The incretory function of the pancreas in patients with pulmonary tuberculosis and diabetes mellitus]

Serum C-peptide levels were studied in 88 patients with pulmonary tuberculosis concurrent with diabetes mellitus. The pancreatic incretory function in combined pathology was found to be related both to the type and severity of diabetes mellitus and the severity of tuberculosis. Specific and medicamental intoxication negatively affects residual insulin secretion and the body's insulin-sensitivity. High functional capacity of B-cells of the pancreas and insulin resistance in noninsulin dependent diabetes, on the one hand, and rapid depletion of the insular apparatus in serious chronic tuberculosis, on the other, made it possible to recommend combined hypoglycemic therapy with insulin and oral sugar-lowering drugs to patients with a prolonged severe course of each of the diseases (pulmonary tuberculosis and Type II diabetes) in their combination.     

Oesophageal motility disorders

Oesophageal motility disorders comprise various abnormal manometric patterns which usually present with dysphagia or chest pain. Some, such as achalasia, are diseases with a well defined pathology, characteristic manometric features, and good response to treatments directed at the pathophysiological abnormalities. Other disorders, such as diffuse oesophageal spasm and hypercontracting oesophagus, have no well defined pathology and could represent a range of motility changes associated with subtle neuropathic changes, gastro-oesophageal reflux, and anxiety states. Although manometric patterns have been defined for these disorders, the relation with symptoms is poorly defined and the response to medical or surgical therapy unpredictable. Hypocontracting oesophagus is generally caused by weak musculature commonly associated with gastro-oesophageal reflux disease. Secondary oesophageal motility disorders can be caused by collagen vascular diseases, diabetes, Chagas' disease, amyloidosis, alcoholism, myxo-oedema, multiple sclerosis, idiopathic pseudo-obstruction, or the ageing process.     

Infection and autoimmunity

The development of some autoimmune diseases is increasing in the developed world faster than can be accounted for by genetic change. The development of these autoimmune diseases, such as Type 1 diabetes, is known to be influenced by both genetic and environmental factors. Environmental factors which have been considered to play a role include infectious agents such as viruses or bacteria. The search for a common initiating infection in the aetiology of Type 1 diabetes as proved thus far inconclusive. An alternative way of considering a role for infection is that infection may have historically prevented the development of autoimmune disease. In the developing world changes have occurred such that many chronic infections have been eliminated and this may have led to the emergence of autoimmune pathology. Evidence in support of this hypothesis is considered here and factors governing the development of autoimmunity compared with those which might have influenced the development of childhood leukaemia.     

动脉粥样硬化与骨质疏松——从临床到分子

动脉粥样硬化和骨质疏松都是老年人的常见多发病,严重影响老年人的身心健康,而这两种疾病在临床上常相伴出现。血管钙化是动脉粥样硬化、高血压、糖尿病、血管损伤、慢性肾病和衰老等普遍存在的病理表现,易导致心肌缺血、左心室肥大和心力衰竭,引发血栓形成、斑块破裂,是心脑血管疾病高发生率和高死亡率的重要因素。近年来许多研究提示动脉粥样硬化、血管钙化和骨质疏松之间存在着共同的危险因素、信号转导途径、分子调控机制,而使其互为因果。本文就它们之间的临床联系及发病机制进行初步探讨,为临床工作提供进一步的综合防治理念。     

Epigenetic mechanisms in diabetic vascular complications

There has been a rapid increase in the incidence of diabetes as well the associated vascular complications. Both genetic and environmental factors have been implicated in these pathologies. Increasing evidence suggests that epigenetic factors play a key role in the complex interplay between genes and the environment. Actions of major pathological mediators of diabetes and its complications such as hyperglycaemia, oxidant stress, and inflammatory factors can lead to dysregulated epigenetic mechanisms that affect chromatin structure and gene expression. Furthermore, persistence of this altered state of the epigenome may be the underlying mechanism contributing to a 'metabolic memory' that results in chronic inflammation and vascular dysfunction in diabetes even after achieving glycaemic control. Further examination of epigenetic mechanisms by also taking advantage of recently developed next-generation sequencing technologies can provide novel insights into the pathology of diabetes and its complications and lead to the discovery of much needed new drug targets for these diseases. In this review, we highlight the role of epigenetics in diabetes and its vascular complications, and recent technological advances that have significantly accelerated the field.     

Kidney disease and psoriasis: novel evidences beyond old concepts

Psoriasis is an immune-mediated inflammatory disease for a long time considered as a type of pathology characterized by an exclusive skin involvement. Recently it has been shown that patients affected by this disease have a higher risk of developing comorbidities such as cardiovascular diseases, arterial hypertension, diabetes mellitus, and metabolic syndrome. Even the kidneys can be affected by psoriasis through three different mechanisms: immune-mediated renal damage, drug-related renal damage and chronic renal damage. Renal function should be monitored periodically to minimize the risk of renal adverse events.     

The health of irregular and illegal immigrants: analysis of day-hospital admissions in a department of migration medicine

It is difficult to trace full details of the path which irregular or illegal immigrants follow when seeking assistance in the network of the various hospital departments and health structures. The aim of this work was to analyze the health needs of immigrant people by reviewing the types of treatment given to them in the day-hospital of our Department of Migration Medicine. Our study analyzed day-hospital admissions between 2003 and 2009. The patient charts used for managing day-hospital activity were adopted in 2002 in conformity with the “OSI project”. From these it is possible to draw up a scale picture of the distribution of each pathology in the immigrant population. The sample population consisted of 1,758 subjects, representing 7.4% of potential users. More than half came from Africa, followed by Asia, and then Europe. Gastroenterological diseases ranked first, with dyspeptic syndromes most frequently diagnosed. Infections and parasitic diseases ranked second, and the most frequent diagnoses were sexually transmitted diseases. Third were diseases of the genitourinary system. Metabolic disorders ranked fourth, among them, more than half of the cases were of diabetes mellitus, in patients from south-east Asia. Diseases of the circulatory system were sixth, with hypertension the most frequent pathology. Our data confirm a marked persistence of the phenomenon known as the “healthy immigrant effect” in these types of patients, as well as the prominent role played by “social determinants” in conditioning the health of immigrants, particularly in the case of some infectious diseases.     

From the Cover: Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Aβ deposition in an Alzheimer mouse model with diabetes

Recent epidemiological studies suggest that diabetes mellitus is a strong risk factor for Alzheimer disease. However, the underlying mechanisms remain largely unknown. In this study, to investigate the pathophysiological interaction between these diseases, we generated animal models that reflect the pathologic conditions of both diseases. We crossed Alzheimer transgenic mice (APP23) with two types of diabetic mice (ob/ob and NSY mice), and analyzed their metabolic and brain pathology. The onset of diabetes exacerbated Alzheimer-like cognitive dysfunction without an increase in brain amyloid-β burden in double-mutant (APP⁺-ob/ob) mice. Notably, APP⁺-ob/ob mice showed cerebrovascular inflammation and severe amyloid angiopathy. Conversely, the cross-bred mice showed an accelerated diabetic phenotype compared with ob/ob mice, suggesting that Alzheimer amyloid pathology could aggravate diabetes. Similarly, APP⁺-NSY fusion mice showed more severe glucose intolerance compared with diabetic NSY mice. Furthermore, high-fat diet feeding induced severe memory deficits in APP⁺-NSY mice without an increase in brain amyloid-β load. Here, we created Alzheimer mouse models with early onset of cognitive dysfunction. Cerebrovascular changes and alteration in brain insulin signaling might play a pivotal role in this relationship. These findings could provide insights into this intensely debated association.