C反应蛋白与2型糖尿病及其血管并发症

2型糖尿病的主要病理生理改变为从以胰岛素抵抗(IR)为主伴胰岛素分泌不足到以胰岛素分泌不足为主伴胰岛素抵抗.目前研究认为IR是一种系统性慢性炎性反应,C反应蛋白(CRP)作为非特异性急性期反应蛋白,在IR各阶段普遍升高.升高的CRP又加重糖、脂代谢紊乱,加重内皮功能失调,促进动脉粥样硬化形成,从而促进2型糖尿病及其并发症的发生、发展.因此,研究CRP与2型糖尿病的关系有助于糖尿病并发症的预测及治疗.     

C反应蛋白与2型糖尿病及其血管并发症

2型糖尿病的主要病理生理改变为从以胰岛素抵抗(IR)为主伴胰岛素分泌不足到以胰岛素分泌不足为主伴胰岛素抵抗.目前研究认为IR是一种系统性慢性炎性反应,C反应蛋白(CRP)作为非特异性急性期反应蛋白,在IR各阶段普遍升高.升高的CRP又加重糖、脂代谢紊乱,加重内皮功能失调,促进动脉粥样硬化形成,从而促进2型糖尿病及其并发症的发生、发展.因此,研究CRP与2型糖尿病的关系有助于糖尿病并发症的预测及治疗.     

C反应蛋白与2型糖尿病及其血管并发症

2型糖尿病的主要病理生理改变为从以胰岛素抵抗(IR)为主伴胰岛素分泌不足到以胰岛素分泌不足为主伴胰岛素抵抗.目前研究认为IR是一种系统性慢性炎性反应,C反应蛋白(CRP)作为非特异性急性期反应蛋白,在IR各阶段普遍升高.升高的CRP又加重糖、脂代谢紊乱,加重内皮功能失调,促进动脉粥样硬化形成,从而促进2型糖尿病及其并发症的发生、发展.因此,研究CRP与2型糖尿病的关系有助于糖尿病并发症的预测及治疗.     

脐血干细胞经微创介入下胰腺血管插管移植治疗Ⅱ型糖尿病1例

Ⅱ型糖尿病多见于成年人,尤其是40岁以上的人群,常并发血管并发症(尤其是动脉粥样硬化性心、腩血管病),其占糖尿病群体的大多数(95%),主要病理生理改变为从以胰岛素抵抗为主伴胰岛素分泌不足到以胰岛素分泌不足为主伴胰岛素抵抗.我院开展了干细胞移植,治疗Ⅱ型糖尿病1例后已取得了良好的近期疗效.现结合患者情况进行文献讨论.     

2型糖尿病患者单核细胞内皮黏附功能的改变

2型糖尿病是动脉粥样硬化性疾病的高危因素,2型糖尿病中的高血糖常与其并存的胰岛素抵抗、高胰岛素血症和高甘油三酯血症等均与此有关,但这些代谢异常与动脉粥样硬化之间的联系机制目前还不清楚.单核细胞黏附到血管内皮是动脉粥样硬化在细胞水平的第一步.已有人初步在糖尿病动物模型和糖尿病患者中发现单核细胞对血管内皮的黏附性增强.本研究旨在观察糖尿病患者外周血单个核细胞对培养的血管内皮细胞的黏附性,以及血糖、胆固醇、甘油三酯、胰岛素浓度和体重指数等与该黏附性的关系.     

高脂高蔗糖饲料诱导贵州小香猪发生糖尿病和动脉粥样硬化病变

用贵州小香猪建立一种新的2型糖尿病合并动脉粥样硬化模型，探讨高脂高蔗糖饲料对糖、脂代谢的影响。采用高脂高蔗糖饲料饲喂贵州小香猪，观察其体重、血糖、胰岛素和血脂的变化，并对胰岛β细胞功能、脂质在主动脉和肝脏组织沉积进行研究。结果发现，喂养8个月后，与正常对照组比较：实验组空腹血糖值明显升高．血清总胆固醇、甘油三酯水平升高，脂肪细胞肥大，胰岛β细胞受损，主动脉出现脂纹，内膜增厚，肝脂肪样变性。以上结果说明，高脂高蔗糖饲料可诱导贵州小香猪发生胰岛素抵抗、糖尿病和动脉粥样硬化。此模型适用于糖尿病并发脂代谢紊乱和动脉粥样硬化及其治疗的研究。     

高胰岛素血症与动脉粥样硬化研究现状与进展

糖尿病血管病变是糖尿病的一个最常见的慢性并发症,可累及全身的大血管及微血管,其中大血管病变导致的心脑血管疾病是2型糖尿病患者首要的死亡原因,约占2型糖尿病死因的50％.糖尿病合并大血管病变是目前糖尿病并发症研究的热点,但其具体机制至今尚未完全阐述清楚.本文综述了高胰岛素血症与动脉粥样硬化研究现状与进展,并探讨其引发动脉粥样硬化的可能机制.     

糖尿病的胰岛素治疗

由于糖尿病自然病程的揭示 ,使我们明确了 1型糖尿病发生后 ,不但需外源胰岛素 (ＩＮＳ)控制血糖 ,最终发展到需依赖胰岛素而生存。对 2型糖尿病而言 ,尽管胰岛素抵抗 (ＩＲ)是其发病的主要原因 ,但只要血糖升高到足以诊断糖尿病的程度 ,ＩＲ和胰岛素分泌不足均存在 ,而且随着病程进展 ,胰岛素分泌不足便成为主要矛盾。随病程延长 ,最终需外源胰岛素治疗控制血糖。因此 ,胰岛素治疗几乎是所有糖尿病控制血糖的重要手段。一、2型糖尿病开始联合胰岛素治疗的指征1 .非药物治疗或 (和 )口服药物治疗 ,血糖不能达标 ,均可联合胰岛素治疗。2 .口…     

高胰岛素血症——一个潜在的致冠心病危险因子

从脂质代谢紊乱的角度来看,冠心病可看作是一种代谢性疾病,它的发病机制与内分泌功能紊乱密切相关。大量的临床、流行病学和实验研究表明,不论在糖尿病或在非糖尿病中,高胰岛素水平可导致动脉粥样硬化,高胰岛素血症是一个潜在的致冠心病危险因子。一、临床和流行病学研究 1.糖尿病、胰岛素与冠心病糖尿病是被公认的致冠心病的危险因子,糖尿病不但加速动脉粥样硬化的发展,且使其严重程度增加。糖尿病患者动脉粥样     

高胰岛素血症对平滑肌细胞基因异常甲基化的作用研究进展

调查发现70％的2型糖尿病患者合并动脉粥样硬化,进一步实验证实胰岛素导致血管平滑肌细胞表型转化是导致动脉粥样硬化发生的重要原因之一.平滑肌细胞表型转化已被证实与基因异常甲基化有关,最近发现高胰岛素可以导致平滑肌细胞基因异常甲基化,由此提出假设,血液中高浓度胰岛素可导致血管平滑肌细胞表型转化,最终导致动脉粥样硬化的发生.     

Determinants of coronary vascular disease in patients with type ii diabetes mellitus and their therapeutic implications

Cardiovascular morbidity and mortality are increased 4- to 6-fold in patients with type II diabetes. The high prevalence is multifactorial and reflects in part the adverse influence of covariate, cardiac risk factors such as hypertension and hyperlipidemia. Type II diabetes is characterized by insulin resistance, hyperinsulinemia, and altered carbohydrate and lipid metabolism resulting in hyperglycemia, increased concentrations in blood of very low-density and low-density lipoproteins, and decreased blood high-density lipoproteins. Abnormalities seen predispose to vasculopathy through lipid deposition into vessel walls associated with monocyte infiltration, vascular smooth muscle cell proliferation, arterial mural fibrosis, and thrombosis. Conventional therapy for cardiovascular disease such as angioplasty and bypass surgery are of only limited efficacy. Thus, retardation of progression of atherosclerosis is essential. In addition to focusing on coexistent cardiac risk factors such as hypertension, therapy for patients with type II diabetes should reduce or reverse insulin resistance, improve metabolic control, and, ideally, do so without exacerbating hyperinsulinemia. Diet and exercise are central, and novel orally active hyperglycemic agents such as the biguanides and the thiazolidinediones that sensitize diverse tissues to insulin offer particular promise.     

Diabetic vascular disease: an experimental objective

It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with "prediabetes" have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For >50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.     

Lipids versus glucose in inflammation and the pathogenesis of macrovascular disease in diabetes

Type 1 and type 2 diabetes both accelerate cardiovascular disease, yet the triggers are likely different for the two types of diabetes. Results from large-scale clinical trials suggest that intense blood glucose control can reduce cardiovascular events many years later in patients with type 1 diabetes. In type 2 diabetes, mechanisms related to insulin resistance and obesity may be more prominent in promoting atherosclerosis. In this article, we discuss the potential effects of hyperglycemia and diabetes-induced lipid abnormalities on atherosclerosis, particularly focusing on advanced stages of atherosclerosis and evidence from mouse models. In addition, we discuss new research findings in monocyte/macrophage biology that may present intriguing new areas of research related to diabetes and atherosclerosis.     

Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects

Type 2 diabetes mellitus (T2DM) patients have hyperglycemia and hyperinsulinemia and increased risk of atherosclerosis and acute vascular complications. We have reported elevated circulating tissue factor procoagulant activity (TF-PCA) during hyperglycemia (HG) and hyperinsulinemia (HI) in normal subjects. To evaluate the effect of hyperglycemia and hyperinsulinemia on blood cell activation, we assessed platelet CD40L and P-selectin, monocyte tissue factor (TF), and the formation of monocyte-platelet and neutrophil-platelet aggregates. These were assessed in the resting state and following activation with ADP and thrombin (SFLLRN). Healthy individuals were subjected to 24 h of hyperglycemia and hyperinsulinemia, selective hyperglycemia, selective hyperinsulinemia, or normal glucose and insulin. Platelet CD40L expression increased with high glucose/high insulin, selective hyperglycemia and selective hyperinsulinemia. Monocyte-platelet aggregates increased with high glucose/high insulin. Monocyte TF expression increased with high glucose/high insulin and with selective hyperinsulinemia. Upon stimulation with ADP and SFLLRN, monocyte-platelet and neutrophil-platelet aggregates, platelet CD40L and P-selectin, and monocyte TF increased compared to the resting state but was not different between 0 and 24 h, indicating that the responsiveness to those agonists was not altered.Conclusions: Hyperglycemia-hyperinsulinemia in healthy individuals induced platelet activation and monocyte TF expression promoting a procoagulant and proinflammatory state that may contribute to acute vascular events and atherogenesis. Platelet responsiveness to activation with ADP or SFLLRN appears not to be altered by hyperglycemia-hyperinsulinemia.     

Novel therapeutic strategies for the treatment of Type 2 diabetes

Diabetes mellitus is the most common endocrine disease, accounting for over 200 million people affected worldwide. It is characterized by a lack of insulin secretion and/or increased cellular resistance to insulin, resulting in hyperglycemia and other metabolic disturbances. People with diabetes suffer from increased morbidity and premature mortality related to cardiovascular, microvascular and neuropathic complications. The Diabetes Control and Complication Trial (DCCT) has convincingly demonstrated the relationship of hyperglycemia to the development and progression of complications and showed that improved glycemic control reduced these complications. Although the DCCT exclusively studied patients with Type 1 diabetes, there is ample evidence to support the belief that the same relationship between metabolic control and clinical outcome exists in patients with Type 2 diabetes. Therefore, a major effort should be made to develop and implement more effective treatment regimes. This article reviews those novel drugs that have been recently introduced for the management of Type 2 diabetes, or that have reached an advanced level of study and will soon be proposed for preliminary clinical trials. They include: (i) compounds that promote the synthesis/secretion of insulin by the β-cell; (ii) inhibitors of the α-glucosidase activity of the small intestine; (iii) substances that enhance the action of insulin at the level of the target tissues; and (iv) inhibitors of free fatty acid oxidation. © 1998 John Wiley & Sons, Ltd.     

Low bodyweight Type 2 diabetes in India: Clinical characteristics and pathophysiology

Low body weight Type 2 DM/Type 2 DM-lean is a distinct clinical entity that is neither related clinically or pathophysiologically to LADA nor former fruste of Type 1DM, having absence of markers for autoimmune destruction of β-cells and good insulin and C-peptide reserve for a prolonged period of life. They constitute an independent variant of Type 2 DM with inherent peculiarities of insulin kinetics in the liver along with altered profile and behaviour of key enzymes related to carbohydrate metabolism which are marked by excess extraction of insulin in hepatic bed, hyperactive cytochrome system and non-supressible glucokinase activity. These peculiarities are reflected in the peripheral circulation as states of low circulating levels of insulin, hyperglycemia, dyslipidemia without low high density lipoprotein cholesterol (HDLc), raised triglycerides (Tg), low levels of plasma homocysteine and BMI below 19 make these diabetics less prone to develop macrovascular disease. Peripheral neuropathy and the consequences of poor glycemic control such as increased succeptibility to infections and endothelial dysfunction manifesting as proteinuria dominate the clinical picture. In view of more of infective complications and coexistent severe hyperglycemia (glucose toxicity) many of these diabetics may not respond to OHA adequately at the initiation of therapy. However, due presence of insulin resistance and good β-cell reserve for insulin, despite of lean habitus, most of them respond well to OHA for long periods of life, as may be comparable with any other phenotype of Type 2 diabetes. The insulin resistance observed in Type 2 DM-lean is not consequent to anthropometric parameters like central obesity and WHR as these diabetics are lean with poor fat depot and thus it could be an integral part of the pathogenic mechanism of Type 2 DM per se.     

Cardiometabolic risk management in type 2 diabetes and obesity

Type 2 diabetes has become an epidemic in the United States, mainly due to an increase in obesity and sedentary lifestyle. Diabetes is considered a cardiovascular risk equivalent, and cardiovascular death remains the most common cause of death in this population. The cardiovascular complications of diabetes, beginning as early as 10 years before the development of frank hyperglycemia, are strongly linked to the development of insulin resistance and the ensuing metabolic disarray often referred to as the metabolic syndrome. To provide proper therapy for cardiovascular prevention, the down-stream effects of insulin resistance must be understood. The most important aspect of treating patients with the metabolic syndrome is the realization that treatment must begin before the development of frank hyperglycemia, particularly if cardiovascular events are to be avoided. Thus, in addition to managing the hyperglycemia that develops with the onset of diabetes, insulin resistance, dyslipidemia, and hypertension must also be properly addressed.     

Novel therapy for type 1 diabetes: Autologous hematopoietic stem cell transplantation

Type 1 diabetes is characterized pathologically by autoimmune insulitis‐related islet β‐cell destruction. Although intensive insulin therapy for patients with type 1 diabetes can correct hyperglycemia, this therapy does not prevent all diabetes‐related complications. Recent studies have shown that autologous hematopoietic stem cell transplantation (HSCT) is a promising new approach for the treatment of type 1 diabetes by reconstitution of immunotolerance and preservation of islet β‐cell function. Herein we discuss the therapeutic efficacy and potential mechanisms underlying the action of HSCT and other perspectives in the clinical management of type 1 diabetes.     

The stepwise approach to the management of type 2 diabetes

As the prevalence of type 2 diabetes continues to increase worldwide, there is an enhanced need for effective disease management. Type 2 diabetes is managed through a stepwise program of intensive therapy that consists of lifestyle modifications and sequential addition of oral antihyperglycemic agents and insulin as necessary. Successful implementation of this approach lessens the microvascular complications of the disease and promotes a lifestyle that may reduce macrovascular complications and comorbidities. Because of the progressive pancreatic beta-cell failure that causes hyperglycemia in type 2 diabetes, many people with type 2 diabetes will ultimately require insulin for disease management. Insulin may be used alone or in combination with oral agents to achieve glycemic control with a minimum of side effects. Although disease management regimens must be tailored to the needs of the individual with type 2 diabetes, the health care provider should always employ an aggressive, treat-to-target strategy to lower hyperglycemia and lessen diabetes-related risk factors.     

Many patients with Type 1 diabetes estimate their prandial insulin need inappropriately

Background: Many factors contribute to the need for prandial insulin in Type 1 diabetes. However, patients’ success in achieving normal postprandial glucose concentration is understudied. The aim of the present study was to determine how often patients with Type 1 diabetes achieve normal postprandial glucose concentrations and to evaluate factors associated with postprandial hypo‐ and hyperglycemia. Methods: Data on food intake, physical activity, insulin administration, and blood glucose concentration were collected using a self‐administered questionnaire from 331 patients with Type 1 diabetes (43% men; mean age 49 ± 12 years; mean diabetes duration 32 ± 13 years). Of these, 179 provided data on blood glucose concentrations measured 110–150 min postprandially. One such meal per patient was randomized for analyses. Results: Hypoglycemia (<4.0 mmol/L), normoglycemia (4.0–7.9 mmol/L), and hyperglycemia (≥8.0 mmol/L) were observed after 23%, 36%, and 41% of meals, respectively. The three postprandial glycemia groups did not differ with respect to the meal composition or the timing of the postprandial blood glucose measurement. In women, postprandial hyperglycemia was associated with shorter diabetes duration and higher preprandial blood glucose concentration, whereas postprandial hypoglycemia was associated with higher physical activity. No single factor explained the postprandial glycemic state in men. Conclusions: A total of 64% of patients estimated their prandial insulin need inappropriately, suggesting that estimation of the optimal prandial insulin dose is not easy, even after a long duration of diabetes.