黄 斌，罗 琳，韩文群，谢 雪，罗先策，魏 东
关键词：马来酸罗格列酮
【摘要】 目的 通过观察马来酸罗格列酮治疗2型糖尿病患者改善糖脂代谢、胰岛素抵抗的同时，血清C反应蛋白、肿瘤坏死因子-α水平的变化，探讨该药对炎症因子与糖脂代谢、胰岛素抵抗的影响。方法 采用随机方法将82例已应用口服降糖药物的2型糖尿病患者分为治疗组(马来酸罗格列酮4mg/d 磺脲类和双胍类)、对照组(磺脲类和双胍类)，进行为期12周的治疗观察，其间若无低血糖发生，则磺脲类和双胍类剂量保持不变，保持相对稳定的饮食及运动。测定治疗前后空腹和标准餐后血糖、胰岛素、C肽水平、糖化血红蛋白(HbA1C)水平、血脂、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平，血尿常规、肝肾功能、计算胰岛素抵抗指数(HOMA-IR)。结果 治疗12周后治疗组空腹和餐后血糖、空腹胰岛素、C肽、HbA1c、甘油三酯、CRP、HOMA-IR有显著下降，P＜0.05，餐后胰岛素下降差异有极显著性，P＜0.01，HDL-C有显著升高，P＜0.05，胆固醇、LDL-C、TNF-α水平有所下降，但差异无显著性，P＞0.05；对照组空腹和餐后血糖、HbA1C有显著下降，P＜0.05，胰岛素、C肽、胆固醇、甘油三酯、LDL-C、CRP、HOMA-IR、TNF-α有所下降，但差异无显著性，P＞0.05，HDL-C无显著升高。治疗组与对照组比较，胰岛素、餐后C肽、甘油三酯、HDL-C、CRP、HOMA-IR差异有显著性，P＜0.05，血糖、HbA1c、空腹C肽、胆固醇、LDL-C、TNF-α差异无显著性，P＞0.05。结论 研究发现，马来酸罗格列酮与口服降糖药联合治疗2型糖尿病，可显著降低空腹和餐后血糖、糖化血红蛋白，同时餐后胰岛素水平下降尤为显著，胰岛素抵抗指数也有显著下降，并伴有甘油三酯的降低和HDL-C的升高。同时使C反应蛋白水平显著下降，TNF-α也有所下降，通过调节炎症因子稳定血管内皮功能。因而对防止β细胞功能衰竭及糖尿病血管并发症的发生有较好的疗效。
【关键词】 马来酸罗格列酮；胰岛素抵抗；C反应蛋白；肿瘤坏死因子-α
The effects of rosiglitazone on lipid and glucose metabolism，insulin resistance and inflammatory factors in type 2 diabetic patients
【Abstract】 Objective To explore the effects of rosiglitazone on improving lipid and glucose metabolism，insulin resistance and reducing CRP(C-reactive protein)，TNF-alpha(tumor necrosis factor-alpha)in patients with type 2 diabetes mellitus.Methods Eighty-two diabetic patients were randomized to receive either SU(sulphonylurea)plus Met(metformin)therapy of additional treatment with rosiglitazone 4mg per day for 12 weeks.Based on glycemic response，SU/Met doses was maintained or reduced for symptomatic hypoglycemia.The primary end points were measured at baseline and after 12 weeks.Furthermore，insulin resistance was estimated by calculating HOMA-IR(homeostasis model assessment of insulin resistance).Results After 12 weeks，treatment with rosiglitazone combination significantly reduced fasting and postprandial plasma glucose，insulin，C-peptide，HbA1c（hemoglobin A1c），triglyceride，CRP and HOMA-IR(P＜0.05)，whereas HDL-C(high density lipoprotein cholesterol)was significantly increased(P＜0.05)，and slight reduction were observed but not statistically significantly in total cholesterol，LDL-C(low density lipoprotein cholesterol)and TNF-alpha(P＞0.05).In control group，fasting and postprandial plasma glucose and HbA1c were reduced significantly(P＜0.05) but had no significant effect on insulin，C-peptide，cholesterol，triglyceride，LDL-C，HDL-C，CRP，TNF-alpha and HOMA-IR (P＞0.05).At the end of treatment，compared to the SU-Met-treated group，treatment with rosiglitazone combination significantly reduced insulin，C-peptide，triglyceride，HDL-C，CRP and HOMA-IR(P＜0.05).However，there were no statistical differences in blood sugar，HbA1c，cholesterol，LDL-C and TNF-alpha(P＞0.05) between the groups.Conclusion Our 12-week study suggests that for type 2 diabetic patients treated with established SU plus Met therapy，the addition of rosiglitazone not only improved glycemic control，serum lipid profiles and insulin sensitivity，but also has anti-inflammatory effects by reducing the levels of CRP and TNF-alpha，ameliorating endothelial function.
【Key words】 maleic rosiglitazone；insulin resistance；c-reactive protein；tumor necrosis factor-α
2型糖尿病发病的关键因素是胰岛素抵抗和进行性β细胞功能衰竭。近几年的研究表明慢性炎症可能与胰岛素抵抗并进而发展为糖尿病有关。有报道一些炎症因子在多种组织中能影响血糖，抑制胰岛素的生物活性［1］。马来酸罗格列酮是噻唑烷二酮类药物，其对改善糖脂代谢、胰岛素抵抗都有较好的疗效，而对C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平的影响及其与胰岛素抵抗的关系如何，本研究对此作了观察及分析。
1 资料与方法
1.1 一般资料 入选要求：(1)符合WHO标准确诊的2型糖尿病患者；(2)排除肝肾功能不良、合并心功能不全、感染、脑血管意外的患者；(3)均为口服降糖药物磺脲类(SU)和双胍类治疗(剂量：小到中量)；(4)空腹血糖(FBG)＞7.0mmol/L，餐后血糖(PBG)>9.0mmol/L，糖化血红蛋白水平(HbA1c）＞6.5%的患者共82例。随机分为两组，治疗组为马来酸罗格列酮 SU和双胍类、对照组为SU和双胍类。两组患者一般情况比较见表1。
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