炎症与2型糖尿病

胰岛素抵抗（IR）和胰岛素分泌不足是2型糖尿病（T2DM）发病的两个关键因素，但其机制尚未阐明。近年来炎症学说备受关注，认为T2DM为一先天性免疫和低度慢性炎症性疾病。在T2DM的易感个体，随着老龄化和营养过剩等环境因素的作用，先天性免疫系统被激活，巨噬细胞、脂肪细胞等前哨细胞分泌TNF-α、IL-6等多种炎症因子，进而引起IR、胰岛素分泌功能障碍和代谢综合征的发生。先天性免疫系统的激活可能是TEDM和动脉粥样硬化发生的共同机制之一。近年来大量研究支持该学说。     

2型糖尿病心外膜脂肪:冠心病新的防治靶点

异位脂肪的过量堆积是2型糖尿病（T2DM)发生冠心病的高危因素。心外膜脂肪（EAT）是紧邻心肌和冠状动脉的一种异位脂肪。在T2DM患者体内，EAT的容积和功能学发生变化，通过分泌脂肪因子、炎症因子和游离脂肪酸等，促进冠状动脉的内皮及平滑肌发生胰岛素抵抗、损伤和炎症反应，并引起心肌的损伤，进而加快冠心病的发生及发展，增加心肌缺血和斑块破裂等冠心病事件的发生。现有证据表明EAT可能是T2DM合并冠心病的治疗靶点，本文将对这一领域的研究进展进行总结及展望。     

2型糖尿病与炎症及抗炎疗法

在2型糖尿病（Type 2 diabetes mellitus，T2DM）的发病机制中，胰岛素抵抗（Insulinresistence。IR）和胰岛B细胞功能障碍是两个重要环节。虽然其确切的发病机制尚未完全阐明，但越来越多的证据提示T2DM及其并发症的发生同炎症密切相关，T2DM是一种自然免疫和慢性亚临床炎症疾病；而且抗炎治疗可以改善T2DM患糖代谢异常、提高胰岛素敏感性。祖国中医也逐渐显示出其重要作用。     

NLR、PLR、MLR在2型糖尿病及其并发症中应用的研究进展

2型糖尿病（T2DM）是一种多发且严重威胁人类健康的代谢性疾病,慢性炎症在T2DM的发生、发展及其并发症发生中起重要作用。作为炎症标记物,与单个炎症标记物相比,中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、单核细胞与淋巴细胞比值（MLR）可更稳定地衡量慢性炎症程度和炎症细胞比例。越来越多的证据表明,NLR、PLR及MLR与T2DM胰岛素抵抗及糖代谢异常密切相关,在T2DM慢性并发症如糖尿病肾病、视网膜病变、周围神经病变、糖尿病足溃疡及骨质疏松的发展、预后及转归中起重要作用,并对T2DM合并动脉粥样硬化、心力衰竭及急性脑梗死的严重程度及预后有一定预测价值。     

NOD1 受体、NOD2 受体与糖尿病的关系研究进展

糖尿病是由多种致病因素共同作用于机体引起的以慢性高血糖为主要临床特点的全身慢性代谢性疾病,可以累及多个系统和脏器。其中胰岛素抵抗（IR）是2型糖尿病（T2DM）的重要机制,贯穿于T2DM的整个发生、发展过程中。近年来,炎症被公认为是联系肥胖、IR和T2DM的重要病理生理过程。最新研究拉0发现,IR、T2DM的发生、发展与天然免疫的激活启动的慢性低度炎症有关。     

胰岛素抵抗与IKK和JNK活性的改变

胰岛素抵抗（IR）和胰岛素分泌不足是T2DM的两个关键因素,但机制未明。近年炎症学说备受关注,认为T2DM为一先天性免疫和低度慢性炎症性疾病。在T2DM的易感个体,随着老龄化和营养过剩等环境因素的作用,先天性免疫系统被激活,巨噬细胞、脂肪细胞等前哨细胞分泌肿瘤坏死因子α（TNF-α）、白介素6（IL-6）、抵抗素等多种细胞因子,进而引起IR、胰岛素分泌功能障碍和代谢综合征。     

2型糖尿病血管内皮功能的变化与他汀类药物的调节作用

内皮功能障碍在2型糖尿病（T2DM）患者并发症的发生和发展过程中起着非常重要的作用。高糖、血脂代谢异常、胰岛素抵抗等均能通过各种直接或间接途径如促炎症效应,内皮型一氧化氮（NO）合酶和NO活性改变,氧化应激,胰岛素介导的信号转导通路异常等导致内皮功能障碍,而他汀类药物可能通过影响这些途径从而在总体上调节T2DM患者的内皮功能。     

胰岛素强化治疗对2型糖尿病患者静息能量消耗的影响

目的观察胰岛素强化治疗对2型糖尿病（T2DM）患者静息能量消耗（REE）的影响。方法对26例T2DM患者经胰岛素强化治疗前后的『临床生化指标、炎症因子及REE进行比较分析。结果胰岛素强化治疗能显著降低REE,用体重（wt）校正后REE／Wt下降约10．4％（P=0．006）。多元回归分析提示REE与FPG、高敏C反应蛋白（hsDRP）、白介素6（IL-6）正相关（P〈0．05）。结论胰岛素强化治疗可降低T2DM患者的REE,REE的降低与血糖下降及炎症反应的改善相关。     

新诊断2型糖尿病患者血清淀粉样蛋白的变化

测定73例正常对照组,38例糖尿病前期（IGR）组,46例初诊2型糖尿病（T2DM）组的SAA水平。结果：（1）IGR组、T2DM组SAA水平较正常对照组增加,差异具有统计学意义（P〈0.05）;（2）T2DM组与IGR组比较,SAA升高,差异具有统计学意义（P〈0.05）。结论新诊断T2DM患者确实存在炎症因子SAA的升高,SAA在T2DM的发生中,可能具有致病作用。     

2型糖尿病患者血清抵抗素水平与血糖和炎症因子的关系

目的探讨2型糖尿病（DM）患者血清抵抗素水平与血糖及炎症因子的相关性。方法采用酶联免疫分析法检测35例初诊2型DM患者、27例血糖控制良好2型DM患者（HbA1C〈7％）、22例呼吸道感染患者及20名糖耐量正常的健康对照者空腹血清抵抗素、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）水平，同时监测空腹血糖、胰岛素、C反应蛋白（CRP）水平及体重指数（BMI）。结果初诊2型DM组血清抵抗素、胰岛素、各炎症因子及血糖水平均高于健康对照组（均P〈0．01），而血糖控制良好2型DM组抵抗素和IL-6水平与健康对照组差异无统计学意义；感染组抵抗素、各炎症因子水平显著高于其它各组（P〈0．01）。相关分析显示抵抗素水平与性别、BMI和空腹胰岛素等均不相关，但与空腹血糖（r=0．38，P=0．03）及炎症因子IL-6（r=0．31，P=0．02）、TNF—α（r=0．48，P=0．03）、CRP（r=0．70，P=0．01）呈显著正相关，与总胆固醇呈显著负相关（r=-0．19，P=0．04）。结论人类空腹血清抵抗素水平在2型DM患者中明显升高，其与血糖浓度有关，并可能受炎症因子的影响，藉此参与2型DM炎症发病机制，但与肥胖关系不明显。     

Inflammation as a link between obesity,metabolic syndrome and type 2 diabetes

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammatory therapies could have a place in prevention and treatment of type 2 diabetes.     

Neuroendocrine mechanisms in insulin resistance

Dysregulated hormonal, metabolic and neural signalling within and between organs can contribute to development of metabolic diseases including type 2 diabetes. Insulin-antagonistic effects of hormones, cytokines and excess metabolic substrates such as glucose and fatty acids may be exerted via common mechanisms involving for example reactive oxygen species (ROS) accumulation and associated inflammatory responses. Visceral adiposity is a central component of the metabolic syndrome and it is also strongly associated with insulin resistance. Both visceral obesity and insulin resistance are important risk factors for the development of type 2 diabetes. In the development of insulin resistance, it is likely that intra-abdominal adipose tissue plays a critical role in a complex endocrine and neural network involving several tissues. This review paper focuses on neuroendocrine 'stress' factors that target insulin-responsive tissues, in particular adipose tissue. We propose that there are common pathways by which dysregulation in different endocrine systems may contribute to the development of type 2 diabetes.     

Association of syndromes of insulin resistance with coronary artery disease

Insulin resistance and its associated conditions, type 2 diabetes mellitus and the metabolic syndrome, have assumed great public health significance in relation to the development of atherosclerotic coronary artery disease. While the overall incidence of coronary artery disease has been declining, its incidence has been increasing in populations with insulin resistance. When insulin resistance is present in conjunction with type 2 diabetes mellitus and/or the metabolic syndrome, as well as other risk factors, the chance of developing coronary artery disease is strikingly increased as are the frequency and severity of its complications. In these situations, insulin resistance may behave synergistically with other risk factors. In addition to clustering with conventional risk factors, more recent evidence indicates that insulin resistance is linked with 'non-traditional' coronary artery disease risk factors and possibly with a pro-atherosclerotic inflammatory state.     

Transforming growth factor-beta 1 levels in women with prior history of gestational diabetes mellitus

It is known that women with prior history of gestational diabetes mellitus (pGDM) feature obesity, insulin resistance and endothelial dysfunction which cause premature atherosclerosis. Transforming growth factor-beta 1 (TGF-beta1) is a key cytokine in obesity and insulin resistance and also play important roles in the development of atherosclerosis. This study was conducted to demonstrate the serum TGF-beta1 levels of people with pGDM. Thirty women with pGDM, 20 women with type 2 diabetes mellitus (T2DM) and 20 healthy women were enrolled. Serum TGF-beta1 levels of people with pGDM were found to be significantly higher than healthy controls and significantly lower than women with T2DM. TGF-beta1 levels were found to be correlated with postprandial glucose and age and inversely correlated with body mass index (BMI) and waist circumference. On multiple regression analysis postprandial glucose level, age and BMI were determined as the most important factors affecting TGF-beta1 levels. This study demonstrates elevated TGF-beta1 levels in pGDM. The inflammatory response to hyperglycemia and insulin resistance could be the major factors for the increased expression of TGF-beta1.     

Aktuelles zu den molekularen Grundlagen der Ern?hrung

The increase in type 2 and type 1 diabetes over the last decades is likely due to altered environmental and lifestyle factors. High glycemic index-diets cannot induce type 1 diabetes but may accelerate its progression in the presence of islet cell autoimmunity. Vitamin D supplementation appears to reduce type 1 diabetes risk. Diet and exercise improve insulin resistance and mitochondrial function characteristic for risk groups, but are impaired by variations in the PPARδ and NDUFB6 genes. Ingestion of coffee and black tea may reduce the risk of type 2 diabetes, while plant ingredients like resveratrol and berberine reduced insulin resistance and fat accumulation through activating mitochondrial function in animal studies. Low-glycemic diets reduce both postprandial insulinemia and release of inflammatory markers, which are involved in the development of insulin resistance and type 2 diabetes. Dietary modification is therefore essential in pathogenesis but also an important starting point for future strategies in the prevention and therapy of diabetes.     

Pre-diabetes,insulin resistance,inflammation and CVD risk

There is accumulating evidence that insulin resistance in the pre-diabetic state is associated with the presence of additional cardiovascular risk factors and increased incidence of cardiovascular disease (CVD). There is also accumulating evidence indicating that chronic sub-clinical inflammation as measured by such inflammatory markers as C-reactive protein (CRP) is associated with insulin resistance and other features of the insulin resistance syndrome, increased risk of development of type 2 diabetes and increased cardiovascular event risk. Insulin-sensitizing agents may have greater effects in reducing cardiovascular risk than secretagogues in the pre-diabetic state, and glitazones have been found to decrease CRP levels in patients with diabetes. Statins also reduce CRP levels. Efforts to reduce CVD should include increased emphasis on improving glycaemic control, preventing development of diabetes and addressing cardiovascular risk factors in the pre-diabetic state.     

脂肪组织局部肾素-血管紧张素系统的调节及其在糖尿病中的作用

脂肪组织局部存在肾素-血管紧张素系统(RAS)中几乎所有的组分,这些组分不仅构成局部RAS,而且是循环中RAS各成分的重要来源.多种因素包括肥胖、胰岛素等均可以影响脂肪组织中RAS各成分的表达.脂肪组织局部RAS活性增加,可作用于脂肪细胞,抑制脂肪细胞分化及脂质代谢,并影响脂肪细胞因子分泌,同时血管紧张素可作用于周围组...     

脂肪组织局部肾素-血管紧张素系统的调节及其在糖尿病中的作用

脂肪组织局部存在肾素-血管紧张素系统(RAS)中几乎所有的组分,这些组分不仅构成局部RAS,而且是循环中RAS各成分的重要来源.多种因素包括肥胖、胰岛素等均可以影响脂肪组织中RAS各成分的表达.脂肪组织局部RAS活性增加,可作用于脂肪细胞,抑制脂肪细胞分化及脂质代谢,并影响脂肪细胞因子分泌,同时血管紧张素可作用于周围组织,通过加重炎性反应和氧化应激等途径,导致胰岛素抵抗,参与糖尿病的病理过程.     

Obesity, inflammation, and insulin resistance

Weight gain and obesity are major risk factors for conditions and diseases ranging from insulin resistance and type 2 diabetes mellitus to atherosclerosis and the sequelae of nonalcoholic fatty liver disease. A chronic, subacute state of inflammation often accompanies the accumulation of excess lipid in adipose tissue and liver (hepatic steatosis), evidenced by changes in both inflammatory cells and biochemical markers of inflammation. These changes can be seen in the involved tissues and systemically, in terms of elevated circulating levels of inflammatory markers. The link between obesity and inflammation has therefore raised the important question of whether obesity-induced inflammation plays a pathogenic role in the development and progression of these disorders. We review the rapidly expanding body of animal and clinical data that support potential roles for inflammation in the pathogenesis of insulin resistance and type 2 diabetes mellitus.     

Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?

The importance of understanding insulin action is emphasized by the increasing prevalence of insulin resistance in various populations and by the fact that it plays an important pathophysiological role in many common disorders, for example, diabetes, obesity, hypertension and dyslipidemia. The primary factors responsible for the development of insulin resistance are so far unknown, although both genetic and environmental factors are involved. The genetic defects responsible for the common forms of insulin resistance, for example, in type 2 diabetes, are largely unidentified. Some studies from our group as well as by other investigators suggest that cellular insulin resistance is reversible and that it may be secondary to factors in the in vivo environment. These may include insulin-antagonistic action of hormones like catecholamines, glucocorticoids, sex steroids and adipokines as well as dysregulation of autonomic nervous activity and they could contribute to the early development of insulin resistance. Some of these factors can directly impair glucose uptake capacity and this might be due to alterations in key proteins involved in insulin's intracellular signaling pathways. This article briefly summarizes proposed mechanisms behind cellular and whole-body insulin resistance. In particular, we question the role of intrinsic defects in insulin's target cells as primary mechanisms in the development of insulin resistance in type 2 diabetes and we suggest that metabolic and neurohormonal factors instead are the main culprits.