Ovalle Fernando, Bell David S H
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
Diabetes Care. 2004 Nov;27(11):2585-9. doi: 10.2337/diacare.27.11.2585.
In a previous study, we found observational evidence of improvement in beta-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study.
A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide.
Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA(1c) was well matched between groups before treatment (8.7 +/- 0.3 and 9.0 +/- 0.3%; NS) and at the end of the 6 months (7.8 +/- 0.5 and 7.8 +/- 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 microIU x ml(-1) x 10 min(-1); P < 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group.
Rosiglitazone, but not insulin, induced a recovery of pancreatic beta-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity.
在之前的一项研究中，我们发现当罗格列酮添加到由磺脲类药物和二甲双胍组成的失效口服降糖方案中时，有观察性证据表明β细胞功能得到改善。为了证实我们之前的观察结果，我们设计并进行了一项前瞻性、随机对照研究。
共有17例2型糖尿病患者，在格列美脲和二甲双胍的最大剂量口服降糖双药方案治疗下血糖控制不佳，被随机分为在其治疗方案中添加罗格列酮或胰岛素，为期6个月。在基线和6个月时，进行了以下检查：测量空腹血糖、空腹胰岛素原和胰岛素水平；频繁采样静脉葡萄糖耐量试验；以及胰高血糖素刺激试验以检测C肽。
9例患者被随机分配添加8mg罗格列酮，8例患者被随机分配在晚餐前注射一次胰岛素（预混70/30）。治疗组在年龄、糖尿病病程和体重指数方面匹配良好。最重要的是，治疗前两组间糖化血红蛋白（HbA1c）水平匹配良好（分别为8.7±0.3%和9.0±0.3%；无显著性差异），6个月结束时也是如此（分别为7.8±0.5%和7.8±0.3%；无显著性差异）。6个月后，在研究结束时，罗格列酮组对葡萄糖的急性胰岛素反应有显著改善（增加15.3微国际单位·毫升-1·10分钟-1；P<0.001），导致处置指数从基线时的0.18增加到6个月时的4.18（P=0.02）。此外，在研究结束时，罗格列酮组胰岛素原与胰岛素的比值下降了36%（P=0.03），而胰岛素治疗组无显著变化。
罗格列酮而非胰岛素可诱导胰腺β细胞功能恢复，在口服降糖治疗失败的2型糖尿病患者中，对葡萄糖第一相胰岛素反应的恢复、处置指数的改善以及胰岛素原与胰岛素比值的降低都证明了这一点。这种改善与糖毒性的纠正无关。
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