脂联素与2型糖尿病及其大血管病变

脂联素与肥胖、胰岛素抵抗、2型糖尿病及其大血管病变的发生、发展有密切关系,被认为是一种保护性因子.本文从多方面就脂联素与2型糖尿病及其大血病变的关系加以总结.脂联素具有胰岛素抵抗及拮抗动脉粥样硬化的作用,对脂联素在2型糖尿病及其大血管病变方面的基础及临床研究,为改善胰岛素抵抗和防治2型糖尿病大血管病变提供了新的思路.     

脂联素与2型糖尿病及其大血管病变

脂联素与肥胖、胰岛素抵抗、2型糖尿病及其大血管病变的发生、发展有密切关系，被认为是一种保护性因子。本文从多方面就脂联素与2型糖尿病及其大血病变的关系加以总结。脂联素具有胰岛素抵抗及拮抗动脉粥样硬化的作用，对脂联素在2型糖尿病及其大血管病变方面的基础及临床研究，为改善胰岛素抵抗和防治2型糖尿病大血管病变提供了新的思路。     

脂联素与胰岛素抵抗的研究进展

胰岛素抵抗是2型糖尿病、动脉粥样硬化及肥胖症等疾病的共同病理基础，脂联素是近年来新发现的，由脂肪细胞分泌的蛋白质，其血浆水平的降低是发生胰岛素抵抗和糖尿病的独立危险因素。本文综述了脂联素分泌的调控因素和脂联素在胰岛素抵抗和糖尿病中增加胰岛素敏感性的作用机制。     

脂联素与动脉粥样硬化

脂联素是新近发现的脂肪细胞特异性蛋白,研究显示脂联素与胰岛素抵抗关系密切,并且脂联素通过抑制内皮细胞粘附分子的表达、内皮细胞及平滑肌细胞的增殖、巨噬细胞向泡沫细胞转变、参与终止与动脉粥样硬化有关的炎症反应,以及改善脂肪代谢等发挥其抗动脉粥样硬化的作用。对脂联素在抗动脉粥样硬化方面的基础及临床研究,为防治糖尿病大血管并发症提供了一个新的思路。     

脂联素与2型糖尿病及其并发症

脂联素是由脂肪细胞分泌的一种细胞因子,在肥胖症、2型糖尿病及动脉粥样硬化疾病患者体内血浆胞联素水平低于正常。脂联素具有降低血糖、血脂及改善胰岛素抵抗的作用,同时也可拮抗动脉粥样硬化的形成。过氧化物酶体增殖物激活受体γ配体及β-肾上腺素能受体激动剂等因素可增加脂联素的表达及分泌。脂联素的研究将为临床防治2型糖尿病及其并发症提供新的思路。     

脂联素与2型糖尿病及其并发症

脂联素是由脂肪细胞分泌的一种细胞因子，在肥胖症、2型糖尿病及动脉粥样硬化疾病患者体内血浆脂联素水平低于正常。脂联素具有降低血糖、血脂及改善胰岛素抵抗的作用，同时也可拮抗动脉粥样硬化的形成。过氧化物酶体增殖物激活受体γ配体及β-肾上腺素能受体激动剂等因素可增加脂联素的表达及分泌。脂联素的研究将为临床防治2型糖尿病及其并发症提供新的思路。     

脂联素与动脉粥样硬化

脂联素是新近发现的脂肪细胞特异性蛋白，研究显示脂联素与胰岛素抵抗关系密切，并且脂联素通过抑制内皮细胞粘附分子的表达、内皮细胞及平滑肌细胞的增殖、巨噬细胞向泡沫细胞转变、参与终止与动脉粥样硬化有关的炎症反应，以及改善脂肪代谢等发挥其抗动脉粥样硬化的作用。对脂联素在抗动脉粥样硬化方面的基础及临床研究，为防治糖尿病大血管并发症提供了一个新的思路。     

2型糖尿病合并肥胖患者脂联素水平与胰岛素抵抗的相关性

目的 研究2型糖尿病合并肥胖患者脂联素水平和胰岛素抵抗之间的相关性,探讨脂联素在2型糖尿病合并肥胖患者发生胰岛素抵抗中的作用.方法 选择30例2型糖尿病合并肥胖患者、25例2型糖尿病患者及25例非糖尿病对照人员(其中13例为肥胖者),检测体质指数、腰/臀比值、空腹血糖、糖化血红蛋白、血清空腹胰岛素、血脂、脂联素水平,计算胰岛素抵抗指数和胰岛素敏感指数.分析血清脂联素与胰岛素抵抗的相关性.结果 (1)糖尿病肥胖组的检测体质指数、糖化血红蛋白、空腹血糖、胰岛素抵抗指数、血清空腹胰岛素、腰/臀比值均高于对照肥胖组,脂联素、胰岛素敏感指数低于对照肥胖组(P<0.05).(2)糖尿病非肥胖组甘油三酯、糖化血红蛋白、空腹血糖、胰岛素抵抗指数、血清空腹胰岛素均高于对照非肥胖组,胰岛素敏感指数、脂联素低于对照非肥胖组(P<0.05).(3)糖尿病肥胖组甘油三酯、胆固醇、体质指数、糖化血红蛋白、空腹血糖、胰岛素抵抗指数、血清空腹胰岛素、腰/臀比值均高于糖尿病非肥胖组,胰岛素敏感指数、脂联素低于糖尿病非肥胖组(P<0.05).结论 脂联素与2型糖尿病肥胖患者的胰岛素抵抗发生有关,脂联素降低易导致胰岛素抵抗,脂联素水平可作为2型糖尿病合并肥胖患者发生胰岛素抵抗的监测标准.     

2型糖尿病患者一级亲属血清脂联素水平及相关因素研究

糖尿病存在明显的家族遗传易感性。糖尿病一级亲属（FDR）的患病率较一般人群高5～21倍。胰岛素抵抗是2型糖尿病的重要致病因素，有遗传易感性的个体（如有2型糖尿病家族史者）早期即可能存在胰岛素抵抗。脂联素与动脉粥样硬化、胰岛素抵抗、肥胖等疾病存在重要相关性。本研究选取2型糖尿病患者的一级亲属为研究对象，探讨脂联素水平及其影响血浆脂联素水平的相关因素。     

脂联素与冠状动脉粥样硬化

脂联素 (adiponectin)是由脂肪细胞特异分泌的一种蛋白质 ,肥胖者、糖尿病、冠心病患者血浆脂联素水平明显下降。脂联素与胰岛素抵抗密切相关 ,具有抗动脉粥样硬化形成、抗炎症和损伤后抗内膜增生的特性。补充脂联素可能是对上述疾病的一种新的治疗手段。     

Adiponectin: action, regulation and association to insulin sensitivity

Adiponectin is a novel adipocyte-specific protein, which, it has been suggested, plays a role in the development of insulin resistance and atherosclerosis. Although it circulates in high concentrations, adiponectin levels are lower in obese subjects than in lean subjects. Apart from negative correlations with measures of adiposity, adiponectin levels are also reduced in association with insulin resistance and type 2 diabetes. Visceral adiposity has been shown to be an independent negative predictor of adiponectin. Thus, most features of the metabolic syndrome's negative associations with adiponectin have been shown. Adiponectin levels seem to be reduced prior to the development of type 2 diabetes, and administration of adiponectin has been accompanied by lower plasma glucose levels as well as increased insulin sensitivity. Furthermore, reduced expression of adiponectin has been associated with some degree of insulin resistance in animal studies indicating a role for hypoadiponectinaemia in relation to insulin resistance. The primary mechanisms by which adiponectin enhance insulin sensitivity appears to be through increased fatty acid oxidation and inhibition of hepatic glucose production. Adiponectin levels are increased by thiazoledinedione treatment, and this effect might be important for the enhanced insulin sensitivity induced by thiazolidinediones. In contrast, adiponectin levels are reduced by pro-inflammatory cytokines especially tumour necrosis factor-alpha. In summary, adiponectin in addition to possible anti-inflammatory and anti-atherogenic effects appears to be an insulin enhancer, with potential as a new pharmacologic treatment modality of the metabolic syndrome and type 2 diabetes.     

Antiatherosclerotic and Anti-Insulin Resistance Effects of Adiponectin: Basic and Clinical Studies

Adiponectin is a protein secreted by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Obesity-related disorders characterized by insulin resistance including the metabolic syndrome, diabetes, atherosclerosis, hypertension, and coronary artery disease are associated with both decreased adiponectin levels and endothelial dysfunction. Recent studies demonstrate that adiponectin has insulin-sensitizing effects as well as antiatherogenic properties. Lifestyle modifications and some drug therapies to treat atherosclerosis, hypertension, diabetes, and coronary heart disease have important effects in increasing adiponectin levels, decreasing insulin resistance, and improving endothelial dysfunction. In this review, we discuss insights into the relationships between adiponectin levels, insulin resistance, and endothelial dysfunction that are derived from various therapeutic interventions. The effects of lifestyle modifications and cardiovascular drugs on adiponectin levels and insulin resistance suggest plausible mechanisms that may be important for understanding and treating atherosclerosis and coronary heart disease.     

Adiponectin and cardiovascular disease: response to therapeutic interventions

Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Obesity-related disorders including the metabolic syndrome, diabetes, atherosclerosis, hypertension, and coronary artery disease are associated with decreased plasma levels of adiponectin, insulin resistance, and endothelial dysfunction. Adiponectin has insulin-sensitizing effects as well as antiatherogenic properties. Lifestyle modifications and some drug therapies to treat atherosclerosis, hypertension, and coronary heart disease have important effects to simultaneously increase adiponectin levels, decrease insulin resistance, and improve endothelial dysfunction. In this review, we discuss insights into the relationships between adiponectin levels, insulin resistance, and endothelial dysfunction that are derived from various therapeutic interventions. The effects of lifestyle modifications and cardiovascular drugs on adiponectin levels and insulin resistance suggest plausible mechanisms that may be important for treating atherosclerosis and coronary heart disease.     

Adiponectin and cardiovascular disease: response to therapeutic interventions.

Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Obesity-related disorders including the metabolic syndrome, diabetes, atherosclerosis, hypertension, and coronary artery disease are associated with decreased plasma levels of adiponectin, insulin resistance, and endothelial dysfunction. Adiponectin has insulin-sensitizing effects as well as antiatherogenic properties. Lifestyle modifications and some drug therapies to treat atherosclerosis, hypertension, and coronary heart disease have important effects to simultaneously increase adiponectin levels, decrease insulin resistance, and improve endothelial dysfunction. In this review, we discuss insights into the relationships between adiponectin levels, insulin resistance, and endothelial dysfunction that are derived from various therapeutic interventions. The effects of lifestyle modifications and cardiovascular drugs on adiponectin levels and insulin resistance suggest plausible mechanisms that may be important for treating atherosclerosis and coronary heart disease.     

Adiponectin: An adipokine linking adipocytes and type 2 diabetes in humans

Adipocyte-derived adiponectin is an insulin-sensitizing and antiatherosclerotic hormone, and replenishment of adiponectin in animal models ameliorated insulin resistance and atherosclerosis. In humans, recent studies have demonstrated that adiponectin level is a good predictor of developing type 2 diabetes and coronary artery disease. Decreasing level of adiponectin is caused by the interaction between genetic factors, such as single nucleotide polymorphisms in the adiponectin gene, and environmental factors, such as high-fat diet. Agents that increase blood level of adiponectin or enhance the actions of adiponectin can be an ideal medicine for ameliorating insulin resistance and type 2 diabetes.     

2型糖尿病高尿酸患者动脉粥样硬化与白细胞介素10和脂联素的关系

目的探讨2型糖尿病高尿酸血症患者动脉粥样硬化与血清白细胞介素10(IL-10)和脂联素之间的关系。方法分别检测2型糖尿病高尿酸患者合并动脉粥样硬化65例(高尿酸组)、2型糖尿病患者合并动脉粥样硬化68例(尿酸正常组)、正常对照组30例的血尿酸、血清IL-10和脂联素等指标,分析与动脉粥样硬化的关系。结果高尿酸组、尿酸正常组血清IL-10水平显著低于正常对照组,高尿酸组血清IL-10水平低于尿酸正常组;高尿酸组、尿酸正常组血清脂联素水平显著低于正常对照组,高尿酸组血清脂联素水平低于尿酸正常组;相关分析显示:内膜中膜厚度与IL-10、脂联素呈负相关,与稳态模型法胰岛素抵抗指数、血尿酸呈正相关。多元线性逐步回归分析显示,进入回归方程的因素有IL-10、脂联素、血尿酸、甘油三酯、低密度脂蛋白胆固醇、稳态模型法胰岛素抵抗指数、收缩压和糖化血红蛋白。结论血清IL-10、脂联素水平降低与胰岛素抵抗、高尿酸血症密切相关,共同参与了糖尿病动脉粥样硬化的发生发展。     

血浆脂联素与2型糖尿病胰岛素抵抗关系的研究

目的　测定 2型糖尿病患者血浆脂联素的水平 ,并分析它与体重指数、血糖、胰岛素、血脂和胰岛素抵抗的关系 ,从而探讨脂联素在糖尿病发病中的作用。方法　健康对照组 2 8例 ,2型糖尿病组 60例 ,根据体重指数又将糖尿病组分为非肥胖糖尿病组 3 0例 (BMI <2 5kg/m2 )和肥胖糖尿病组 3 0例 (BMI >2 5kg/m2 )。用ELISA方法检测空腹血浆脂联素浓度 ,同时测定各组的空腹血糖、胰岛素、血脂的水平 ;根据HOMA模型提出的公式 ,计算分析胰岛素抵抗指数 ,并分析各指标间的相关性。结果　 (1)糖尿病各组血浆脂联素的水平明显低于正常对照组 ,且肥胖糖尿病组脂联素的水平低于非肥胖组 ,差异均有显著性 (P 0 .0 1) ;(2 )血浆脂联素浓度与体重指数、空腹胰岛素、胰岛素抵抗指数 (IR)、甘油三酯呈显著负相关。结论　脂联素参与了胰岛素抵抗的发生过程 ,与糖尿病的发生发展密切相关 ;脂联素可作为评价胰岛素抵抗程度的一种新的敏感指标     

The role of adiponectin signaling in metabolic syndrome and cancer

The increased prevalence of obesity has mandated extensive research focused on mechanisms responsible for associated clinical complications. Emerging from the focus on adipose tissue biology as a vitally important adipokine is adiponectin which is now believed to mediate anti-diabetic, anti-atherosclerotic, anti-inflammatory, cardioprotective and cancer modifying actions. Adiponectin mediates these primarily beneficial effects via direct signaling effects and via enhancing insulin sensitivity via crosstalk with insulin signaling pathways. Reduced adiponectin action is detrimental and occurs in obesity via decreased circulating levels of adiponectin action or development of adiponectin resistance. This review will focus on cellular mechanisms of adiponectin action, their crosstalk with insulin signaling and the resultant role of adiponectin in cardiovascular disease, diabetes and cancer and reviews data from in vitro cell based studies through animal models to clinical observations.     

Adipokines in diabetes and cardiovascular diseases

Recent studies suggest that adipocyte-secreted factors called adipokines are involved in obesity-associated complications including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Among those, adiponectin is an antidiabetic and antiatherogenic protein, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. In contrast, leptin, tumor necrosis factor a, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 are upregulated in obesity and contribute to the development of diabetes and vascular disease. In this review, the relevance of adipokines in obesity, insulin resistance, diabetes mellitus, atherosclerosis, and cardiovascular diseases is discussed.     

Role of adiponectin in insulin-resistant hypertension and atherosclerosis.

Insulin resistance is one of the major risk factors associated with development of hypertension and atherosclerosis. Recent studies have shown that adiponectin, an adipocyte-derived hormone, may be involved in insulin resistance and development of atherosclerosis in diabetes patients. The aim of this study was to examine adiponectin levels in patients with essential hypertension to determine the relationships between adiponectin levels and insulin sensitivity and to examine the relationship of adiponectin with pulse wave velocity (PWV) in a general population based on the results of an epidemiological survey in Japan. In a clinical study, 20 normotensives (NT) and 30 non-treated essential hypertensives (EHT) were hospitalized, and euglycemic hyperinsulinemic glucose clamp (GC) was performed to evaluate insulin sensitivity defined as M value. EHT were divided into insulin-resistant EHT (EHT-R) and insulin-nonresistant EHT (EHT-N) according to the mean -1 SD of the M value of NT as a cut-off point. Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and adiponectin concentrations were measured. There were no significant differences in body mass index (BMI) or FPG among the NT, EHT-N, and EHT-R groups. The M value and adiponectin concentration in EHT-R were significantly lower than those in the NT or EHT-N. The IRI level in the EHT-R was significantly higher than those in the other groups. A positive correlation between adiponectin concentration and M value was found in all subjects, and adiponectin concentration and M value were found to be significant determinants of each other in multiple regression analysis. In an epidemiological study, we studied 391 male inhabitants of rural communities in Hokkaido, Japan. Systolic blood pressure (SBP), BMI, FPG, IRI, and adiponectin were measured in all subjects early in the morning. Homeostasis model assessment (HOMA) values were calculated as an index of insulin sensitivity, and PWV was used as an index of atherosclerosis. A negative correlation between HOMA values and adiponectin concentration was found in all of the subjects. Multiple regression analysis revealed that adiponectin was a significant determinant for PWV in subjects less than 70 years of age. The results of the clinical study indicate that EHT-R had not only hyperinsulinemia but also a low concentration of adiponectin. The results of multiple regression analysis for determinants of degree of PWV using data obtained in the epidemiological study suggest that adiponectin plays a role in antiatherosclerosis, partly through improvement of insulin resistance.