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題 名 | 胰島素增敏劑--thiazolidinediones=Insulin Sensitizer--Thiazolidinediones |
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作 者 | 蕭淑華; 游新; 吳達仁; | 書刊名 | 內科學誌 |
卷 期 | 12:2 2001.04[民90.04] |
頁 次 | 頁54-61 |
分類號 | 418.271 |
關鍵詞 | 胰島素增敏劑; Insulin sensitizer; |
語 文 | 中文(Chinese) |
中文摘要 | 第2型糖尿病以胰島功能不足和周邊組織對胰島素抗性為病態生理特徵。藥物治療 方面三十幾年來以磺胺尿素劑 (sulfonylurea) 與雙胍類 (biguanide) 為傳統治療。 近年 來繼α - 配糖酵素抑制劑 (α -glucosidase inhibitors) 發展之後, 被稱為胰島素增敏 劑 (insulin sensitizer) 之 thiazolidinediones 類口服抗高血糖劑也迅速被發展出來。 Thiazolidinediones 主要是作用在胰島素主要的標的器官; 即肝臟、骨骼肌與脂肪組織。 在分子級作用機制上, 作用在所謂 peroxi- some proliferator-activated receptor gamma (PPAR- γ ) 的細胞核內接受器結合。此類藥物也堪稱屬 PPAR 相關的藥物治療學全 新領域之指標藥物。 Thiazolidinediones( 或稱 glitazones) 族員包括:troglitazone、 rosiglitazone 與 pioglitazone。 在相當的治療劑量下, 三者均可比安慰劑組發揮下降 HbAlc 達 1 %以上的療效。 Thiazolidinediones 治療第 2 型糖尿病幾週後,不僅血糖得 以降低,血中游離脂肪酸與三酸甘油酯也會下降;而血中高密度脂蛋白膽固醇則會增加。這 類藥物對其他動脈硬化的諸多危險因素也有改善效果。藥物的副作用中最常被提及是水腫, 其他有上呼吸道感染、頭痛、肌肉疼痛、和水腫等。肝毒性是最被大家關心的,截至目前之 臨床觀察顯示 rosiglitazone 與 pioglitazone 是安全的。 英國前瞻性糖尿病研究 (United Kingdom Prospective Diabetes Study) 顯示第 2 型糖尿病患者,強化血糖控制 可以減少糖尿病併發症的發生。然而要有效地控制血糖,多種藥物治療是必經的途徑。 Glitazones 單一藥物治療是被確定的。 與他類抗高血糖藥間的並用,也沒有重要的藥物間 交互引起之不良反應。倒是適當地並用,可互取所長;進而改善血糖控制。然而 glitazones 類藥物是否比其他藥物更能兼改善第 2 型糖尿病患之大血管病變與微細血管病 變之罹患率與死亡率,則有待進一步的實證醫學研究來確立。者 |
英文摘要 | Thiazolidinediones are a new class of oral antidiabetic agents (also called as glitazones) that acts primarily by decreasing insulin resistance in peripheral tissues in patients with type 2 diabetes mellitus. Unlike sulfonylureas, glitazones are not insulin secratagogues. Glitazones act as agonist for peroxisome proliferator-activated receptor- gamma (PPAR γ )receptors, which are abundant in tissues such as adipose tissue, skeletal muscle, and liver. Activation of PPAR γ nuclear receptors modulates the transcription of lots of insulin responsive genes involved in the control of glucose and lipid metabolism. Pharmacological studies indicate that glitazones improve sensitivity of insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. All glitazones treated groups experienced improved glycemic control (decreased fasting blood glucose and HbA1c levels) compared with placebo. The treatments were also associated with slight decreases in circulating insulin levels, suggesting an improvement in insulin sensitivity. Compared with placebo, the glitazones-treated groups experienced reductions in free fatty acids. The first marketed glitazone, troglitazone, was withdrawn last year due to hepatotoxicity and death secondary to hepatic failure. Rosiglitazone and pioglitazone, which are new and more potent members of glitazones, seem safe from the currently available data. |
本系統中英文摘要資訊取自各篇刊載內容。