Yudkin J S, Panahloo A, Stehouwer C, Emeis J J, Bulmer K, Mohamed-Ali V, Denver A E
Department of Medicine, University College London Medical School, Whittington Hospital, UK.
Diabetologia. 2000 Sep;43(9):1099-106. doi: 10.1007/s001250051500.
AIMS/HYPOTHESIS: Improved glycaemic control might reduce both microvascular and macrovascular complications of Type II diabetes (non-insulin-dependent) mellitus. To explore such possible mechanisms, we investigated the effects of intensive treatment on markers of endothelial dysfunction and of acute phase activation, using both sulphonylureas and insulin.
In a randomised cross-over study we gave sulphonylureas or insulin each for a period of 16 weeks to 22 poorly controlled Type II diabetic subjects who were being treated by diet. There was a 4 week washout period between each treatment. Subjects were studied at baseline and at the end of each treatment.
Treatment with sulphonylureas and insulin resulted in similar improvements in glycaemic control (glycated haemoglobin, baseline: 11.8 [(SD 2.2)%; after sulphonylureas: 8.6 (1.2)%,p < 0.001; after insulin: 8.6 (1.2)%, p < 0.001] and in insulin sensitivity ¿metabolic clearance rate of glucose, baseline: median 1.75 [interquartile (IQ) range 1.41, 2.27] ml x kg(-1) x min(-1); after sulphonylureas: 2.41 (1.82, 3.01) ml x kg(-1) x min(-1), p = 0.001; after insulin: 2.23 (1.92, 2.75) ml x kg(-1) min(-1), p = 0.027¿. There were no significant changes in concentrations of endothelial markers von Willebrand factor, cellular fibronectin, thrombomodulin, tissue plasminogen activator, soluble E-selectin or soluble intercellular adhesion molecule-1 or in urinary albumin excretion rate after either treatment period. Concentrations of C-reactive protein were not significantly influenced by sulphonylureas but fell after insulin [baseline: median 4.50 (IQ range 1.37, 6.44) microg x ml(-1); sulphonylureas: 2.69 (0.88, 9.65) microg x ml(-1) (p = 0.53); insulin: 2.07 (1.16, 5.24) microg x ml(-1) (p = 0.017)]. There were, however, no significant effects of either treatment on circulating concentrations of fibrinogen (p = 0.28-0.34) or of the proinflammatory cytokines interleukin-6 or tumour necrosis factor-alpha (p = 0.65-0.79).
CONCLUSION/INTERPRETATION: Markers of endothelial dysfunction and concentrations of proinflammatory cytokines in Type II diabetes are not influenced by improved glycaemic control over 16 weeks. Improved metabolic control with insulin could, however, be associated with reduced concentrations of the acute phase marker C-reactive protein.
目的/假设：改善血糖控制可能会降低II型糖尿病（非胰岛素依赖型）的微血管和大血管并发症。为探究此类可能的机制，我们使用磺脲类药物和胰岛素，研究强化治疗对内皮功能障碍标志物和急性期激活标志物的影响。
在一项随机交叉研究中，我们将磺脲类药物或胰岛素分别给予22名通过饮食治疗但血糖控制不佳的II型糖尿病患者，各治疗16周。每次治疗之间有4周的洗脱期。在基线和每次治疗结束时对受试者进行研究。
磺脲类药物和胰岛素治疗使血糖控制（糖化血红蛋白，基线：11.8[(标准差2.2)%；磺脲类药物治疗后：8.6(1.2)%，p<0.001；胰岛素治疗后：8.6(1.2)%，p<0.001]以及胰岛素敏感性——葡萄糖代谢清除率方面得到类似改善，基线：中位数1.75[四分位间距（IQ）范围1.41,2.27]ml·kg⁻¹·min⁻¹；磺脲类药物治疗后：2.41(1.82,3.01)ml·kg⁻¹·min⁻¹，p = 0.001；胰岛素治疗后：2.23(1.92,2.75)ml·kg⁻¹·min⁻¹，p = 0.027）。在任一治疗期后，内皮标志物血管性血友病因子、细胞纤连蛋白、血栓调节蛋白、组织型纤溶酶原激活物、可溶性E选择素或可溶性细胞间黏附分子-1的浓度以及尿白蛋白排泄率均无显著变化。磺脲类药物对C反应蛋白浓度无显著影响，但胰岛素治疗后其浓度下降[基线：中位数4.50（IQ范围1.37,6.44）μg·ml⁻¹；磺脲类药物治疗后：2.69(0.88,9.65)μg·ml⁻¹（p = 0.53）；胰岛素治疗后：2.07(1.16,5.24)μg·ml⁻¹（p = 0.017）]。然而，两种治疗对纤维蛋白原的循环浓度（p = 0.28 - 0.34）或促炎细胞因子白细胞介素-6或肿瘤坏死因子-α的循环浓度均无显著影响（p = 0.65 - 0.79）。
结论/解读：II型糖尿病中内皮功能障碍标志物和促炎细胞因子浓度不受16周改善血糖控制的影响。然而，胰岛素改善代谢控制可能与急性期标志物C反应蛋白浓度降低有关。
