Chaiken R L, Eckert-Norton M, Pasmantier R, Boden G, Ryan I, Gelfand R A, Lebovitz H E
Department of Medicine, State University of New York, Health Science Center, Brooklyn 11203, USA.
Diabetologia. 1995 Nov;38(11):1307-12. doi: 10.1007/BF00401763.
Insulin resistance is a significant pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM). A new class of drugs, the thiazolidinediones, have been shown to lower blood glucose levels without stimulating insulin secretion. We report the metabolic effect of the thiazolidinedione, darglitazone, in obese NIDDM subjects. Nineteen subjects were enrolled in a double-blind placebo-controlled study in which 25 mg of darglitazone was given once a day for 14 days. Nine subjects received the active drug and ten subjects received placebo. Darglitazone-treated subjects showed; 1) a decrease in 24-h plasma glucose area under the curve from 292.8 +/- 31.2 to 235.2 +/- 21.6 mmol.h-1.l-1 p = 0.002; 2) a decrease in 24-h serum insulin area under the curve from 1027.2 +/- 254.4 to 765.6 +/- 170.4 microU.h-1.l-1 p = 0.045; 3) a decrease in 24-h non-esterified fatty acid area under the curve from 1900 +/- 236 to 947 +/- 63 g.h-1.l-1 p = 0.002; 4) a decrease in mean 24-h serum triglyceride by 25.9 +/- 6.2% as compared to -3.9 +/- 4.8% for the placebo-treated group, p = 0.012. Placebo-treated subjects showed no change in their metabolic parameters after treatment. Thus, darglitazone is effective in increasing insulin effectiveness in obese NIDDM subjects. The potential for this and similar drugs to treat or prevent NIDDM as well as the insulin-resistance syndrome needs to be explored.
胰岛素抵抗是非胰岛素依赖型糖尿病（NIDDM）发生发展中的一个重要致病因素。一类新型药物噻唑烷二酮已被证明可降低血糖水平而不刺激胰岛素分泌。我们报告了噻唑烷二酮类药物达格列净对肥胖NIDDM患者的代谢作用。19名受试者参加了一项双盲安慰剂对照研究，其中25毫克达格列净每天服用一次，共14天。9名受试者接受活性药物，10名受试者接受安慰剂。接受达格列净治疗的受试者表现出：1）24小时血浆葡萄糖曲线下面积从292.8±31.2降至235.2±21.6 mmol·h⁻¹·L⁻¹，p = 0.002；2）24小时血清胰岛素曲线下面积从1027.2±254.4降至765.6±170.4 μU·h⁻¹·L⁻¹，p = 0.045；3）24小时非酯化脂肪酸曲线下面积从1900±236降至947±63 g·h⁻¹·L⁻¹，p = 0.002；4）与安慰剂治疗组相比，24小时血清甘油三酯平均降低25.9±6.2%，而安慰剂治疗组为-3.9±4.8%，p = 0.012。接受安慰剂治疗的受试者治疗后代谢参数无变化。因此，达格列净可有效提高肥胖NIDDM患者的胰岛素有效性。需要探索这类药物及类似药物治疗或预防NIDDM以及胰岛素抵抗综合征的潜力。
