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| 題 名 | Long-term Normoglycemic Effect of Glibenclamide in Non-obese Non-insulin Dependent Diabetics=長期使用磺醯脲藥物之降血糖機轉 |
|---|---|
| 作 者 | 倪國彬; | 書刊名 | 醫學研究 |
| 卷 期 | 13:2 1992.09[民81.09] |
| 頁 次 | 頁111-120 |
| 分類號 | 418.271 |
| 關鍵詞 | 降血糖藥物; 磺醯脲; 長期使用; |
| 語 文 | 英文(English) |
| 中文摘要 | 口服降血糖藥物在治療非胰島素依賴型糖尿病人佔有重要之一環,在使用飲食治療、運動等方法失敗後可使用口服降血糖藥物來幫助治療。其中磺醯脲類藥物臨床的使用已超過二十五年,但其降血糖的機轉至今仍有爭議。早期的研究認為其可刺激胰島素分泌及降低肝臟葡萄糖輸出率,繼之的研究則發現此類藥物長期使用後並不能增高血中胰島素濃度。最近的研究顯示,此類藥物長期使用主要能增強細胞胰島素結合後效應,此為胰外效應的一部份。但是這些研究僅約數週至數月不等之短期觀察。 我們的研究在以12位新近診斷非肥胖非胰島素依賴型糖尿病人經過glebenclamide一年半至二年之治療,比較治療前後其血漿糖,飲食後胰島素之反應,基礎肝臟葡萄糖輸出率,及胰島素激發下葡萄糖利用率之改變。結果顯示平均空腹血漿糖自199±16 mg/dl下降至147±9 mg/dl(p<0.01),糖化血色素自7.6±0.4%下降至5.6±0.3%(p<0.01)。平均空腹血漿胰島素濃度上升。另外藉著葡萄糖嵌合試驗合併重氫標化葡萄糖稀釋法,來測定基礎肝臟葡萄糖輸出率及胰島素激發下葡萄糖之利用率。肝臟葡萄糖輸出率呈有意義之下降自2.9±0.1降至2.3±.01 mg/kg/min,且其與空腹血漿糖及糖化血色素之下降均有正相關(r值分別為0.9及0.89)並且改變了肝臟對胰島素之代謝,C肽與胰島素之比值從8.5±0.8降至5.6±.04(p<0.01)。 治療後,胰島素代謝廓清率及葡萄糖利用率未呈有意義改變,但葡萄糖代謝廓清率則自3.4±0.4增至3.9±0.6 mg/kg/min。 結論:非肥胖胰島素依賴性糖尿病人以glibenclamide治療18-24月後,仍可刺激胰島素之分泌,使基礎及飲食後胰島素濃度均上升。在長期使用後降血清作用之胰外效應則包含1. 增加週邊葡萄糖利用率。2. 降低基礎肝臟葡萄糖輸出率。3. 增加胰島細胞分泌胰島素。而降低肝臟葡萄糖輸出率與空腹血漿糖及糖化血色素之下降均呈密切相關,所以胰臟及胰臟外效應在降血糖機轉上都扮演了部份的角色。 |
| 英文摘要 | Although the sulfonylurea have been used in the management of non-insulin-dependent diabetes mellitus (NIDDM) for more than 25 years, the mechanism of its hypoglycemic action still remains controversial. The purpose of study is to elucidate the long-term hypoglycemic effect of glibenclamide (GBC) in patients with NIDDM. Twelve newly diagnosed, non-obese non-insulin-dependent diabetic patients were studied before and after treatment with glibenclamide for 18-24 months. The mean fasting plasma glucose (FPG) fell from an initial vale of 199±16 to 147±9 mg/dl (p<0.01). The corresponding glycosylated hemoglobin (HbAlc) fell from 7.6±0.4 to 5.6±0.3% (0<0.01). The mean fasting insulin secretion after weight-maintenance (30 kcal/kg/day) diet was increased after GBC treatment (23.6±3.0 to 51.1±6.4 uU/ml, p<0.001). Basal hepatic glucose production (HGP) and insulin-mediated glucose uptake were evaluated by glucose clamp study plus [3-3H] Glucose infulion. HGP was reduced significantly from 2.9±0.1 to 2.3±0.1 mg/kg/min (p<0.05). The fall of HGP in each patient had positive correlated with the fall of FPG (r=0.9, p<0.001). The changes of hepatic extraction of insulin, measured by molar ratio of C-peptide to insulin, was reduced from 8.5±0.8 to 5.6±0.4 (p<0.01). The metabolic clearance rate of insulin or glucose disposal rate (Rd) did not change significantly after treatment. But the metabolic clearance rate of glucose (measured by Rd divided by steady-state plasma glucose in glucose clamp study) was increased from 3.4±0.4 to 3.9±0.6 ml/kg/min (p<0.05) after 18 to 24 months of GBC treatment. In conclusion, the basal hyperinsulinemia and increased β-cill secretion after meal was found after 18 to 24 months GBC treatment in non-obese NIDDM patients. The long-term hypoglycemic effect of glibenclamide treatment were suggested due to (1) increasing peripheral utilization of glucose and (2) decreasing hepatic glucose production, and (3) increasing β-cell secretion of insulin. The reduction of HGP was correlated well with FPG and HbAlc. We concluded that both pancreatic and extra pancreatic effect contribute to the glucose-lowering effect of GBC. |
本系統中英文摘要資訊取自各篇刊載內容。