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.     

成纤维细胞生长因子21与糖尿病性大血管病变

成纤维细胞生长因子21(FGF21)是近几年新发现的代谢调节因子,它与糖尿病性大血管病变之间的关系已成为近些年的研究热点。内源性FGF21水平在糖耐量受损时升高,随着2型糖尿病大血管病变的出现,其水平进一步升高,推测其可能机制是FGF21抵抗。血管内皮细胞有FGF21基因表达,且FGF21在动脉粥样硬化早期可能起保护作用,这暗示着FGF21有望成为预防和治疗糖尿病性大血管病变的靶点。     

2型糖尿病患者抑制颈动脉内膜中层厚度进展干预的新进展

2型糖尿病与心血管病的高发病率和病死率有关。在2型糖尿病患者中,应用颈动脉内膜中层厚度(carotid intima-media thickness,CIMT)作为一种替代性研究终点,可能有助于更好地理解动脉粥样硬化的过程以及在预防心血管病事件中干预治疗的效果和CIMT的有效性。日本大阪大学的Yokoya     

自身免疫与糖尿病大血管病变

糖尿病大血管病变是以动脉粥样硬化为主要病理特征的糖尿病慢性并发症之一.近年来,自身免疫因素在动脉粥样硬化发病中的作用越来越受到关注,多种自身抗体、自身抗原和免疫系统成分参与动脉粥样硬化的发生和发展.检测血液中几种自身抗原及其抗体,如氧化型低密度脂蛋白、p2糖蛋白Ⅰ、热休克蛋白的变化,可间接预测糖尿病患者动脉粥样硬化的发生、发展.对糖尿病大血管病变相关自身免疫更深入的研究,将为糖尿病大血管病变的早期诊断、监测和治疗开辟一条新的途径.     

钠-葡萄糖共转运蛋白2抑制剂防治动脉粥样硬化的作用机制

动脉粥样硬化性心血管疾病是2型糖尿病致死、致残的主要原因。钠-葡萄糖共转运蛋白2(SGLT2)抑制剂是一类新型降糖药物,近年来多项大规模随机临床试验证明,此类药物可降低2型糖尿病患者的心血管事件发生风险。目前尚不明确SGLT2抑制剂的心脏保护机制。本文总结SGLT2抑制剂对血管内皮功能、抑制炎症、动脉粥样硬化斑块、动脉粥样硬化危险因素等的影响,探讨其防治动脉粥样硬化的可能机制。     

幽门螺杆菌感染与2型糖尿病患者缺血性心脑血管疾病关系的研究

目的测定144例2型糖尿病（DM）患者和37名健康对照者幽门螺杆菌（Hp）感染率。方法清晨空腹静脉血血清层析法Hp抗体测定。结果发现2型糖尿病患者Hp感染率升高，2型DM伴Hp感染者的冠心病和动脉粥样硬化性脑梗死发病率升高。结论提示Hp感染可能是2型DM患者缺血性心脑血管病变的危险因素之一。     

糖尿病性动脉粥样硬化加速的机制

随着“共同土壤”学说的提出,人们认识到冠心病与代谢综合征（MS）、胰岛素抵抗（IR）、前驱糖尿病（PD）和2型糖尿病（T2DM）存在着共同的发病机制,炎症是其共同的土壤,氧化应激在其中发挥重要作用.糖尿病（DM）与冠心病之间的内在关系即DM性动脉粥样硬化（AS）的作用机制越来越受到研究者的关注.本文主要从氧化应激的角度来阐述MS、IR、PD、T12DM患者AS的加速发生.     

2型糖尿病、动脉粥样硬化与炎症

糖尿病与动脉粥样硬化关系密切,表现为糖尿病患者出现动脉粥样硬化的时间早、程度重和预后差,而出现动脉粥样硬化性心脏病的患者有相当部分出现不同程度的糖调节受损。控制血糖可以明显减少慢性微血管并发症,但不能显著降低动脉粥样硬化所致的大血管并发症。近年的研究提示,2型糖尿病和动脉粥样硬化可能是同一个病理基础上平行发展的两个疾病(图1),糖调节受损的出现意味着导致动脉粥样硬化的危险因素的作用加强。他们的共同基础是慢性、亚临床性的炎症,以图及1炎症导致的胰岛素抵抗[1]。炎症是2型糖尿病和动脉粥样硬化的共同土壤一、炎症导…     

基质金属蛋白酶-2与2型糖尿病血管病变关系的研究进展

糖尿病(DM)已经成为继肿瘤、心血管病变之后第三大严重威胁人类健康的慢性疾病。糖尿病血管病变是糖尿病的主要并发症,且是糖尿病致残致死的主要原因之一。其大血管病变性质为动脉粥样硬化,主要累及主动脉、冠状动脉等大血管;而微血管病变是糖尿病特有的慢性血管并发症,主要表现为肾脏、视网膜等微血管病变。糖尿病血管病变机制与防治研究已成为近年来研究的热点。2型糖尿病(T2DM)的广泛代谢异常引起血管基底膜的结构和功能发生改变,从而使其降解与重构     

血尿酸与老年2型糖尿病动脉粥样硬化的关系

149例老年2型糖尿病患者依据有无动脉粥样硬化斑块分为无动脉斑块组38例、动脉斑块组111例,比较两组血清尿酸水平;再根据血清尿酸水平分为A、B、C、D组,比较四组颈动脉斑块及股动脉斑块发生率。结果随着血清尿酸水平增高,2型糖尿病患者颈动脉、下肢动脉斑块发生率逐渐上升;动脉斑块组血清尿酸水平显著高于无动脉斑块组。尿酸、年龄是2型糖尿病动脉粥样斑块发生的危险因素。结论尿酸与2型糖尿病动脉粥样硬化病变相关,防治糖尿病大血管病变除控制血糖外,应同时重视尿酸水平的控制。     

Significance of microalbuminuria in atherosclerotic vascular disease

Microalbuminuria is considered as a sign of high risk of renal disease in type 1 diabetes mellitus, and of cardiovascular disease in types 1 and 2 diabetes. In recent years numerous studies have suggested that microalbuminuria may be associated with atherosclerotic vascular disease, independently from diabetes mellitus. The presence of microalbuminuria was investigated in 30 patients suffering from atherosclerotic vascular disease: ischemic heart disease, cerebrovascular disease or arterial disease of the lower extremities. They were divided into two groups similar in age: 13 with type 2 diabetes mellitus, and 17 without diabetes. The aim of the research was to reveal eventually different prevalence of microalbuminuria in patients with vascular disease associated with diabetes or without diabetes. Microalbuminuria was present in 52.9% of the non diabetic patients and in 76.9% of the diabetics, but the difference did not reach statistical significance (in Mann-Whitney test p = 0.18; Chi-square test = 0.83; p = 0.3). No significant correlation was found between microalbuminuria and fibrinogen, total cholesterol, HDL-cholesterol and triglycerides. The hypertensive patients presented higher mean values of microalbuminuria than the normotensive ones (3.2 +/- 3.8 and 2.8 +/- 4.4 mg %, respectively), but the difference was again not significant (t = 0.25; p = 0.8). In the light of this research microalbuminuria seems to be a condition associated with atherosclerotic vascular disease, independently from the presence of diabetes mellitus and arterial hypertension.     

The relationship between lipoprotein(a) and the complications of diabetes mellitus

The risk of cardiovascular disease is increased approximately two- to four-fold in patients with diabetes mellitus compared with non-diabetic controls. The nature of this increased risk cannot be completely explained by the contribution of traditional risk factors. As such, there has been a great deal of interest in assessing the role of lipoprotein(a) (Lp(a)), an LDL-like lipoprotein, in the vascular complications of diabetes. Although numerous studies in the non-diabetic population have demonstrated an association between elevated plasma Lp(a) concentration and risk for atherosclerotic disorders, the contribution of Lp(a) to the enhanced risk of vascular disease in the diabetic population is not clearly defined. Herein we review the structure and potential functions of Lp(a), the determination of Lp(a) levels, and the epidemiological evidence supporting its role in coronary heart disease and address the following controversial questions regarding the role of Lp(a) in diabetes mellitus: (1) are plasma Lp(a) levels and phenotype distributions altered in type 1 (insulin-dependent) diabetes mellitus and type 2 (non-insulin-dependent) diabetes mellitus and does the degree of metabolic control influence Lp(a) levels in these patients; (2) what is the relationship between Lp(a) and renal disease in patients with diabetes mellitus; (3) do increased plasma Lp(a) concentrations in patients with diabetes contribute to the vascular complications of this disease; and (4) can the atherogenicity of Lp(a) in diabetes be enhanced in the absence of elevated levels of this lipoprotein due to biochemical modifications. Received: 11 January 2002 / Accepted in revised form: 9 December 2002 Correspondence to S.M. Marcovina     

胰岛素在2型糖尿病合并冠心病中作用的研究进展

与2型糖尿病相关的冠心病的发病率及死亡率呈上升趋势,相关研究表明胰岛素自身可能存在双向性作用,而在2型糖尿病患者中胰岛素对冠状动脉粥样硬化病变的作用仍然存在很大的争议。近年来,多项大型的观察性研究以及少量的随机对照性研究结果也不尽一致。目前,胰岛素在2型糖尿病合并冠心病中的作用机制较为流行“双信号通路”假说。进一步研究和阐明胰岛素在2型糖尿病合并冠心病中的作用显得尤为重要。     

Cardiovascular risk profile and morbidity in subjects affected by type 2 diabetes mellitus with and without diabetic foot

Diabetic foot syndrome (DFS) is the most frequent cause of hospitalization of diabetic patients and one of the most economically demanding complications of diabetes. People with diabetes have been shown to have higher mortality than people without diabetes. On this basis, the aim of our study was to evaluate the possible role of diabetic foot as a cardiovascular risk marker in patients with type 2 diabetes mellitus. We enrolled 102 consecutive patients with type 2 diabetes mellitus with diabetic foot and 123 patients with type 2 diabetes mellitus without limb lesions to compare the prevalence of main cardiovascular risk factors, subclinical cardiovascular disease, previous cardiovascular morbidity, and incidence of new vascular events on a 5-year follow-up. Diabetic patients with diabetic foot were more likely to have a higher prevalence of cardiovascular risk factors such as hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and microalbuminuria or proteinuria, a higher prevalence of a previous cardiovascular morbidity (coronary artery disease, transient ischemic attack/ischemic stroke, diabetic retinopathy), and a higher prevalence of subclinical cardiovascular disease. Furthermore, diabetic patients with foot ulceration showed, on a 5-year follow-up, a higher incidence of new-onset vascular events (coronary artery disease, transient ischemic attack/ischemic stroke, diabetic retinopathy). At multivariate analysis, duration of diabetes, age, hemoglobin A1c, and DFS maintained a significant association with cardiovascular morbidity; but DFS presence showed the highest hazard ratio.     

Combination therapy with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists in the treatment of patients with type 2 diabetes mellitus

Aggressive therapy for patients with type 2 diabetes mellitus and renal disease is warranted given the natural history of this disease. Although antagonizing the renin-angiotensin system is clearly important, how this is accomplished is of considerable controversy. On the one hand, recent clinical trials of patients with type 2 diabetes mellitus with renal disease demonstrate unequivocally the renal protective effect of angiotensin receptor blockers (ARBs). Although the results of the recently published LIFE trial are encouraging, inconsistencies have been observed with ARBs in reducing cardiovascular end points. On the other hand, angiotensin-converting enzyme inhibitors have a dramatic effect in reducing cardiovascular events but have not been shown convincingly to reduce progression of renal disease in patients with type 2 diabetes mellitus. These studies leave us in a quandary as to the optimal initial treatment regimen for patients with type 2 diabetes mellitus and renal disease despite the recent recommendations from the American Diabetes Association (Alexandria, Va). Given the fact that many of these individuals will require administration of multiple antihypertensive agents, perhaps the initial treatment with a combination of an ARB and angiotensin-converting enzyme inhibitor affords optimal cardiovascular and renal protection for patients with type 2 diabetes mellitus and renal disease. Future clinical trials should be designed to address this issue.     

Diabetes mellitus – Risikofaktor für Vorhofflimmern

The relationship between atrial fibrillation and diabetes mellitus type 2 is controversial, and various studies have demonstrated conflicting results. However, the majority of larger prospective studies published during recent years demonstrated a positive correlation. After multivariate adjustment diabetes increased the risk for atrial fibrillation at least two fold. This combination is associated with substantially increased risks of death and cardiovascular events (stroke and heart failure). Atrial fibrillation in patients with diabetes mellitus type 2 identifies individuals who are likely to obtain greater benefits from glycemic control and anticoagulants as well as antihypertensive therapy.     

糖尿病、糖尿病的治疗与心血管病（Ⅰ）

美国心脏联合会（AHA）1999年发表声明提出“糖尿病就是心血管病”的论点,引起了心血管和内分泌糖尿病领域学者们的高度关注。围绕糖尿病和心血管病的相关研究层出不穷,结论也莫衷一是。糖尿病患者是心血管病的高危人群,约有近2／3的糖尿病患者死于心血管病,糖尿病患者其心血管死亡是非糖尿病患者的2～3倍。有关糖尿病和冠心病的关系,有很多研究证据,也有很不相同的研究结果,本文综合具有代表性的临床试验研究,从高血糖与心血管事件、糖尿病是心血管病的等危症、糖尿病不是心血管病的等危症3个方面讨论糖尿病和心血管疾病的关系。     

Diabetic Agents,From Metformin to SGLT2 Inhibitors and GLP1 Receptor Agonists: JACC Focus Seminar

Given the intersection between diabetes mellitus and cardiovascular disease (CVD), pharmacologic agents used to treat type 2 diabetes mellitus must show cardiovascular safety. Comorbid conditions, including heart failure and chronic kidney disease, are increasingly prevalent in patients with diabetes; therefore, they also play a large role in drug safety. Although biguanides, sulfonylurea, glitazones, and dipeptidyl peptidase 4 inhibitors have variable effects on cardiovascular events, sodium glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have consistently shown safety and reduction in cardiovascular events in patients with established CVD. These medications are becoming essential tools for cardioprotection for patients with diabetes and CVD. They may also have roles in primary prevention and renal protection. This paper will review the cardiovascular impact, adverse effects, and possible mechanisms of action of pharmacologic agents used to treat patients with type 2 diabetes.     

Galanin peptide family as a modulating target for contribution to metabolic syndrome

Metabolic syndrome (MetS) is defined as abdominal central obesity, atherogenic dyslipidemia, insulin resistance, glucose intolerance and hypertension. The rapid increasing prevalence of MetS and the consequent diseases, such as type 2 diabetes mellitus and cardiovascular disorder, are becoming a global epidemic health problem. Despite considerable research into the etiology of this complex disease, the precise mechanism underlying MetS and the association of this complex disease with the development of type 2 diabetes mellitus and increased cardiovascular disease remains elusive. Therefore, researchers continue to actively search for new MetS treatments. Recent animal studies have indicated that the galanin peptide family of peptides may increase food intake, glucose intolerance, fat preference and the risk for obesity and dyslipidemia while decreasing insulin resistance and blood pressure, which diminishes the probability of type 2 diabetes mellitus and hypertension. To date, however, few papers have summarized the role of the galanin peptide family in modulating MetS. Through a summary of available papers and our recent studies, this study reviews the updated evidences of the effect that the galanin peptide family has on the clustering of MetS components, including obesity, dyslipidemia, insulin resistance and hypertension. This line of research will further deepen our understanding of the relationship between the galanin peptide family and the mechanisms underlying MetS, which will help develop new therapeutic strategies for this complex disease.     

NASH and the risk of cirrhosis and hepatocellular carcinoma in type 2 diabetes

The risk of chronic liver disease and liver-related mortality is increased in patients with type 2 diabetes mellitus. Several cohort studies have suggested a metabolic pathway from nonalcoholic fatty liver, nonalcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. Although cardiovascular risk remains the major cause for excess mortality in type 2 diabetes mellitus, the risk of progressive liver disease should no longer be underscored.