噻唑烷二酮类药物治疗2型糖尿病的效果

噻唑烷二酮类药物是目前治疗糖尿病的主要药物之一,该类药物可增强机体胰岛素敏感性,降低胰岛素抵抗,在降糖效果上与磺脲类和二甲双胍类相当,但对胰岛B细胞的保护性远远要好于磺脲类和二甲双胍类,而且对心血管有着良好的保护作用。噻唑烷二酮类药物最主要的副作用是水肿和皮下脂肪增多。     

全面认识噻唑烷二酮的临床治疗价值

噻唑烷二酮类药物是改善胰岛素敏感性的新型口服降糖药物,该类药物既能保护胰岛B细胞功能,又能保护心血管,起到抗炎等作用,因此该类药物在临床上得到大量应用。但是该类药物也存在一定不良反应。在选择噻唑烷二酮类药物之前,充分了解患者心血管方面的情况对该类药物进行遴选,可提高治疗所获得的益处,避免其不良反应。     

噻唑烷二酮类药物治疗2型糖尿病的有效性及安全性

噻唑烷二酮类药物是一类新型的治疗2型糖尿病的药物,通过提高机体对胰岛素的敏感性来达到良好控制血糖的作用.噻唑烷二酮类药物还可以有效地降低2型糖尿病患者血中低密度脂蛋白胆固醇、C-反应蛋白、基质金属蛋白酶-9、纤溶酶原激活物抑制剂-11的水平等,提高高密度脂蛋白胆固醇水平,改善血管内皮功能,减少2型糖尿病患者发生心血管疾病的风险.噻唑烷二酮类药物不良反应发生率低,安全性良好.     

噻唑烷二酮类药物治疗2型糖尿病的临床应用

2型糖尿病是以胰岛素抵抗和胰腺β细胞渐进性功能障碍为特征的一类糖尿病。目前，口服降血糖药物有二甲双胍和磺酰脲。近年来，出现了一类治疗糖尿病的新药噻唑烷二酮。它可提高病人对胰岛素的敏感性和改善胰腺β细胞的功能。噻唑烷二酮类药物是一种人工合成的配体，能够结合核过氧化物酶体增殖激活受体γ(PPAR-γ)，激活基因的转录，从而调节脂肪细胞的分化和脂肪细胞的形成，以及葡萄糖和油脂的代谢。目前，对噻唑烷二酮作用的确切分子机制还不太清楚。噻唑烷二酮类药物单独给药或与二甲双胍、磺酰脲及胰岛素合用治疗2型糖尿病，通过快速降低膳后血糖水平，从而改善对血糖生成的控制，并能提高对胰岛素的敏感性。     

知名药师解答“三高”用药

（接上期）53．为什么提倡早期使用噻唑烷二酮类降糖药物？噻唑烷二酮类药物使用至今,临床效果显著,可有效降低空腹血糖3．3～4．5mmol／L,降低糖化血红蛋白1．4％～2．6％,与其他降糖药物联合应用可增强其降糖效果,甚至注射胰岛素的2型糖尿病患者联合应用噻唑烷二酮类药物,也会有明显改善血糖控制的功效。此外,它还能调节血脂紊乱,因而具有减少心血管危险因素及延缓疾病进程的作用。因此,在临床治疗中,对于肥胖或超重的2型糖尿病患者,应优先并尽早给予噻唑烷二酮类药物。早期使用本类药物,决不仅仅意味着血糖、糖化血红蛋白水平和血脂水平的下降和达标,更重要的是其潜在益处在于对胰岛B细胞功能的保护和改善,进而延缓糖尿病患者病情进展,改善诸多心血管危险因素,预防慢性并发症及心血管事件的发生及发展。     

噻唑烷酮类药物治疗缺血再灌注损伤研究

噻唑烷二酮类药物是当今医药界研究的热点之一,已被作为胰岛素增敏剂广泛用于糖尿病和代谢综合征等疾病的治疗。目前研究又发现,这类药物对缺血再灌注损伤有预防和治疗作用,这将为其临床应用开发提供又一广阔的前景。     

胰岛素增敏药吡格列酮的药物动力学概况

吡格列酮属于新一代噻唑烷二酮类抗糖尿病药,化学名为(±)5-[[4-[2-(5-乙基-2-吡啶基)二氧基]苄基]2,4]噻唑烷二酮盐酸盐.20世纪80年代中期由日本武田制药厂开发研制,1999年首先在美国上市,近年来逐渐在我国用于2型糖尿病及代谢综合征的治疗.其作用机制是通过激活核转录因子--过氧化物酶增殖体活化受体γ(PPARγ),调节糖代谢和脂代谢中某些蛋白酶的基因转录,增强肝脏、脂肪、骨骼肌等靶器官对胰岛素的敏感性,从而改善2型糖尿病患者的胰岛素抵抗情况,起到降糖和调脂作用.吡格列酮作为噻唑烷二酮类药物的主要代表之一,具有独特的药物动力学特点.     

罗格列酮治疗2型糖尿病的研究进展

噻唑烷二酮类药物为治疗2型糖尿病开辟了新途径，本文综述了罗格列酮治疗2型糖尿病的研究进展，分别就其作用机制、药理作用、药动学特性、药物相互作用和不良反应作一概述，为临床用药提供参考。     

吡格列酮治疗2型糖尿病的研究进展

胰岛素增敏剂噻唑烷二酮类药物吡格列酮是一种临床上常用的降糖药,本文综述了吡格列酮治疗2型糖尿病的研究进展,主要对其作用机制、药理作用以及与其他药物联用作用效果进行综述,为治疗糖尿病的临床用药和开发新药提供参考。     

噻唑烷二酮类药物对骨作用的利弊比较 ——————- PPARγ2与骨的研究进展

最近,有关噻唑烷二酮类药物的使用又出现了争议,美国食品和药品监督局（ＦＤＡ）甚至要求医生少用或不用该药。两年前,文迪亚导致骨折和心血管事件的报道时有出现。因此,这类药物的治疗作用和副作用成为学术界争论的热点。目前研究表明,PPARγ2在调节糖脂代谢,机体抗炎等方面发挥重要的作用。但最近一些大型临床研究结果显示,TZDs使用可增加绝经后糖尿病老年妇女骨折的风险[1][2]。事物总有它的两面性,这是符合唯物主义辩证法规律的。因此,全方位了解噻唑烷二酮类药物作用对于更好地防治糖尿病,防治骨质疏松等疾病具有重要的现实意义。关于过氧化物酶配体增殖物激活受体γ2（PPARγ2）对骨代谢的影响近年来报道结果众说不一。我们结合自己的工作浅谈这类药物的应用前景。     

Development of insulin resistance and reversal by thiazolidinediones in C2C12 skeletal muscle cells

AIM/HYPOTHESIS: The aim of this study was to develop an insulin-resistant cell culture model in skeletal muscle cell line by chronic presence of insulin in serum-free medium and to determine the effect of thiazolidinediones on insulin signaling. METHODS: We differentiated C2C12 in a combination of serum-free medium in presence or absence of insulin and determined differentiation by creatine kinase activity, myogenin and MyoD expression. The development of insulin resistance was determined by tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1, phosphatidylinositol 3-kinase activity associated with insulin receptor substrate-1 and glucose uptake. We treated the cells with 50 microM of thiazolidinediones to determine the effect on these parameters. RESULTS: C2C12 cells were differentiated normally in the serum-free medium in the absence or presence of insulin. Chronic treatment of insulin resulted in reduced tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1; activation of phosphatidylinositol 3-kinase was impaired and insulin-stimulated glucose uptake was reduced. The treatment of insulin-resistant cells with thiazolidinediones resulted in the enhancement of insulin signaling pathway by increasing tyrosine phosphorylation of insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase activity and glucose uptake. CONCLUSION/INTERPRETATION: These results indicate that insulin resistance can be developed in C2C12 skeletal muscle cell line. These findings implicate a direct mechanism of action of thiazolidinediones on skeletal muscle.     

Comparative safety of newer oral antidiabetic drugs

Oral antidiabetic agents were introduced into clinical practice during the 1950s. Biguanides and sulfonylureas are still used extensively today and their safety and tolerability profiles are well defined. Developments and refinements within these classes have included the introduction of second- and third-generation sulfonylureas, the introduction of modified-release preparations, and the emergence of fixed-dose preparations with metformin and with novel drugs. The latter include the thiazolidinediones, agents with a putative genomic mechanism of action that have been under intense scrutiny since the emergence of severe hepatotoxicity with troglitazone. Recent concerns about thiazolidinediones have centred on the issue of oedema and the risk of precipitating heart failure in vulnerable patients. Only prolonged exposure will determine the long-term safety of thiazolidinediones. Rapid-acting non-sulfonylurea secretagogues appear to be effective and perhaps safer than sulfonylureas in some groups of patients with certain comorbidities (e.g., those with renal impairment). α-Glucosidase inhibitors have an excellent safety record and acarbose has been shown to retard the progression from impaired glucose tolerance to Type 2 diabetes. However, their use is limited by tolerability issues.     

Comparative safety of newer oral antidiabetic drugs

Oral antidiabetic agents were introduced into clinical practice during the 1950s. Biguanides and sulfonylureas are still used extensively today and their safety and tolerability profiles are well defined. Developments and refinements within these classes have included the introduction of second- and third-generation sulfonylureas, the introduction of modified-release preparations, and the emergence of fixed-dose preparations with metformin and with novel drugs. The latter include the thiazolidinediones, agents with a putative genomic mechanism of action that have been under intense scrutiny since the emergence of severe hepatotoxicity with troglitazone. Recent concerns about thiazolidinediones have centred on the issue of oedema and the risk of precipitating heart failure in vulnerable patients. Only prolonged exposure will determine the long-term safety of thiazolidinediones. Rapid-acting non-sulfonylurea secretagogues appear to be effective and perhaps safer than sulfonylureas in some groups of patients with certain comorbidities (e.g., those with renal impairment). alpha-Glucosidase inhibitors have an excellent safety record and acarbose has been shown to retard the progression from impaired glucose tolerance to Type 2 diabetes. However, their use is limited by tolerability issues.     

Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus

Worsening glycaemic control in type 2 diabetes mellitus relates to a decline in beta-cell function, associated with impaired negative feedback regulation of insulin release. Insulin resistance, the 'traditional' cornerstone defect of type 2 diabetes, leads to an array of adverse effects on beta cells, including hypertrophy, apoptosis and those caused by lipotoxicity and glucotoxicity. In particular, increased levels of free fatty acids and their metabolites are thought to diminish both insulin synthesis and glucose-stimulated insulin secretion. Thiazolidinediones are synthetic peroxisome proliferator-activated receptor-gamma agonists that decrease insulin resistance but, as in vitro and in vivo studies suggest, may have direct beneficial effects on pancreatic beta cells. Troglitazone, for example, demonstrated improvements in insulin secretory capacity in isolated pancreatic islets from Wistar rats and a hamster beta-cell line. In vivo studies reveal thiazolidinediones promote beta-cell survival and regranulation as well as maintenance of beta-cell mass and reduction in amyloid deposition. Clinical evidence for thiazolidinediones is largely derived from comparative trials, mainly against sulfonylureas and metformin. Data at 2 years from a number of trials are now available and establish the positive effects of thiazolidinediones on glycaemic control. Empirical evidence showing decreases in fasting plasma insulin levels with pioglitazone and rosiglitazone indicate thiazolidinediones also improve insulin sensitivity. A possible effect of thiazolidinediones on normalising asynchronous insulin secretion, as assessed in a short-term placebo-controlled study, is less established. However, recent and ongoing clinical studies are focusing attention on verifying animal and other data, which support the notion that thiazolidinediones have beneficial effects on beta-cell function. These clinical studies have shown thiazolidinediones capable of preventing or delaying the development of type 2 diabetes in a high-risk population; restoring the first-phase insulin response; and improving secretory responses to oscillations in plasma glucose levels. Many of these effects appear to be independent of improvements in insulin sensitivity. Other research efforts are examining the potential cardiovascular protective effects of thiazolidinediones. Available data imply thiazolidinediones are associated with cardiovascular risk reduction, although results from large, clinical outcome trials, currently in progress, are still needed. Improved understanding of the role that declining beta-cell function has in the development of type 2 diabetes has drawn attention to the need for hypoglycaemic agents that can address this process. Emerging evidence suggests thiazolidinediones offer specific benefits for preventing or delaying the decline in beta-cell function and, thereby, a substrate for early intervention efforts aimed at lowering the worldwide burden of type 2 diabetes.     

PPAR-gamma agonists: therapeutic role in diabetes, inflammation and cancer

The recent development of a novel class of insulin-sensitizing drugs, the thiazolidinediones (TZDs), represents a significant advance in antidiabetic therapy. One key mechanism by which these drugs exert their effects is by activation of the peroxisome proliferator activated receptor γ (PPAR-γ), a member of the nuclear receptor family. Evidence supporting this mechanism of action of the TZDs will be reviewed in this article. Recent data suggests that PPAR-γ agonists might also have therapeutic potential in the treatment of inflammatory diseases and certain cancers.