Voytovich Monica Hagen, Simonsen Cathrine, Jenssen Trond, Hjelmesaeth Jøran, Asberg Anders, Hartmann Anders
Department of Medicine, Section of Nephrology, Laboratory for Renal Physiology, Rikshospitalet University Hospital, 0027 Oslo, Norway.
Nephrol Dial Transplant. 2005 Feb;20(2):413-8. doi: 10.1093/ndt/gfh641. Epub 2004 Dec 22.
Insulin resistance (IR) contributes to the development of glucose intolerance (post-transplant diabetes mellitus or impaired glucose tolerance) following renal transplantation. Furthermore, endothelial dysfunction (ED) is associated with IR. Glucose intolerance, IR and ED are all independent risk factors for cardiovascular disease. Therefore, treatment with insulin sensitizers may benefit glucose-intolerant renal transplant recipients. The main objectives of the present study were to investigate the effect of 4 weeks' treatment with the PPAR-gamma agonist rosiglitazone on insulin sensitivity, plasma glucose and endothelial function in renal transplant recipients with glucose intolerance. Safety parameters were also addressed.
A total of 10 glucose-intolerant renal transplant recipients were treated with rosiglitazone (initially 4 mg/day increasing to 8 mg/day after 1 week). A hyperinsulinaemic euglycaemic glucose clamp, an oral glucose tolerance test and endothelial function assessment with laser Doppler flowmetry were performed both at baseline and at follow-up.
Treatment with rosiglitazone was followed by a significantly improved mean glucose disposal rate (from 6.5 to 9.1 g/kg/min; P = 0.02) and a significant decline in fasting and 2 h plasma glucose (from 6.4 to 5.8 mmol/l, P = 0.01 and from 14.2 to 10.6 mmol/l, P = 0.03, respectively). Furthermore, a significant improvement in endothelial function was demonstrated (AUC(ACh); from 389 to 832 AU x min, P = 0.04). No serious adverse events or hypoglycaemic episodes were observed.
Four weeks' treatment with rosiglitazone was associated with increased insulin sensitivity, lowered fasting and 2 h plasma glucose and improved endothelial function in renal transplant recipients with glucose intolerance. The drug was well tolerated and may be a good alternative for treating these patients.
胰岛素抵抗（IR）促使肾移植后出现葡萄糖不耐受（移植后糖尿病或糖耐量受损）。此外，内皮功能障碍（ED）与IR相关。葡萄糖不耐受、IR和ED均为心血管疾病的独立危险因素。因此，使用胰岛素增敏剂进行治疗可能会使葡萄糖不耐受的肾移植受者获益。本研究的主要目的是调查用过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂罗格列酮治疗4周对葡萄糖不耐受的肾移植受者胰岛素敏感性、血糖和内皮功能的影响。还对安全性参数进行了研究。
总共10名葡萄糖不耐受的肾移植受者接受罗格列酮治疗（初始剂量为4毫克/天，1周后增至8毫克/天）。在基线和随访时均进行了高胰岛素正常血糖葡萄糖钳夹试验、口服葡萄糖耐量试验以及用激光多普勒血流仪评估内皮功能。
罗格列酮治疗后，平均葡萄糖处置率显著提高（从6.5增至9.1克/千克/分钟；P = 0.02），空腹和2小时血糖显著下降（分别从6.4降至5.8毫摩尔/升，P = 0.01；从14.2降至10.6毫摩尔/升，P = 0.03）。此外，内皮功能有显著改善（乙酰胆碱曲线下面积；从389增至832任意单位×分钟，P = 0.04）。未观察到严重不良事件或低血糖发作。
罗格列酮治疗4周可使葡萄糖不耐受的肾移植受者胰岛素敏感性增加、空腹和2小时血糖降低以及内皮功能改善。该药物耐受性良好，可能是治疗这些患者的一个良好选择。
