Tan K C B, Chow W S, Tso A W K, Xu A, Tse H F, Hoo R L C, Betteridge D J, Lam K S L
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, People's Republic of China.
Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR, People's Republic of China.
Diabetologia. 2007 Sep;50(9):1819-1825. doi: 10.1007/s00125-007-0759-0. Epub 2007 Jul 18.
AIMS/HYPOTHESIS: Interfering with the activation of receptor for AGE (RAGE) by using a soluble form of the AGE receptor (sRAGE) prevents or ameliorates the vascular complications of diabetes in experimental studies. Relatively little is known about factors that influence endogenous circulating sRAGE in humans. We investigated the impact of improving glycaemic control on serum total sRAGE and endogenous secretory RAGE (esRAGE), a splice variant of sRAGE, and compared the effect of rosiglitazone with that of sulfonylurea.
A randomised, open-label, parallel group study was performed with 64 participants randomised to receive add-on therapy with either rosiglitazone or sulfonylurea. Serum total sRAGE and esRAGE and metabolic parameters were measured before and after 6 months of treatment.
At 6 months, both rosiglitazone and sulfonylurea resulted in a significant reduction in HbA(1c), fasting glucose and AGE. However, significant increases in total sRAGE and esRAGE were only seen in the rosiglitazone group. As a result, serum esRAGE was higher in the rosiglitazone group than in the sulfonylurea group at 6 months (p < 0.01), whereas the differences in sRAGE between the two groups did not reach statistical significance. Stepwise linear regression analysis showed that treatment modality made a greater contribution than the changes in HbA(1c) to the subsequent changes in esRAGE levels at 6 months.
CONCLUSIONS/INTERPRETATION: Treating type 2 diabetic patients with thiazolidinedione can increase circulating levels of esRAGE and sRAGE. Whether modulation of circulating sRAGE has a beneficial effect on diabetic complications will have to be evaluated in long-term prospective studies.
目的/假设：在实验研究中，使用可溶性晚期糖基化终末产物受体（sRAGE）干扰晚期糖基化终末产物受体（RAGE）的激活可预防或改善糖尿病的血管并发症。关于影响人类内源性循环sRAGE的因素，人们了解相对较少。我们研究了改善血糖控制对血清总sRAGE和内源性分泌型RAGE（esRAGE，sRAGE的一种剪接变体）的影响，并比较了罗格列酮与磺脲类药物的效果。
进行了一项随机、开放标签、平行组研究，64名参与者被随机分配接受罗格列酮或磺脲类药物的附加治疗。在治疗6个月前后测量血清总sRAGE和esRAGE以及代谢参数。
在6个月时，罗格列酮和磺脲类药物均使糖化血红蛋白（HbA1c）、空腹血糖和晚期糖基化终末产物显著降低。然而，仅在罗格列酮组中观察到总sRAGE和esRAGE显著增加。结果，在6个月时，罗格列酮组的血清esRAGE高于磺脲类药物组（p<0.01），而两组之间sRAGE的差异未达到统计学显著性。逐步线性回归分析表明，治疗方式对6个月时esRAGE水平的后续变化的贡献大于HbA1c的变化。
结论/解读：用噻唑烷二酮类药物治疗2型糖尿病患者可提高esRAGE和sRAGE的循环水平。循环sRAGE的调节是否对糖尿病并发症有有益作用，必须在长期前瞻性研究中进行评估。
