GAD treatment and insulin secretion in recent-onset type 1 diabetes
GAD treatment and insulin secretion in recent-onset type 1 diabetes
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DOI：
10.1056/nejmoa0804328
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发表时间：
2008-10-30
影响因子：
158.5
通讯作者：
Casas, Rosaura
中科院分区：
文献类型：
--
作者：
Ludvigsson, Johnny;Faresjo, Maria;Casas, Rosaura
背景：谷氨酸脱羧酶（GAD）的65-kD亚型是1型糖尿病患者的主要自身抗原。这项试验评估了明矾配制的GAD（GAD-alum）来逆转10至18岁患者中新近发作的1型糖尿病。我们将70名空腹C肽水平高于0.1nmol/L的1型糖尿病患者随机分组（0.3 ng/ml）和GAD自身抗体，在接受糖尿病诊断后18个月内招募，在研究第1天和第30天接受20微克GAD-明矾（35名患者）或安慰剂（单独明矾，35名患者）的皮下注射。在第1天和第3、9、15、21和30个月，患者进行混合餐耐受试验以刺激残余胰岛素分泌（以C肽水平测量）。结果：实验组和对照组胰岛素分泌均逐渐减少，而对照组胰岛素分泌明显减少。研究治疗对15个月后空腹C肽水平的变化没有显著影响（主要终点）。空腹C肽水平从基线水平下降，在30个月内，GAD明矾组比安慰剂组明显更少（-0.21与-0.27纳摩尔/升[-0.62与-0.81纳克/毫升]，P=0.045），刺激分泌也是如此，以曲线下面积测量（每升每2小时-0.72 nmol对-1.02 nmol [每毫升每2小时-2.20 ng对-3.08 ng]，P=0.04）。在接受诊断后6个月或更长时间治疗的患者中没有观察到保护作用。不良事件似乎是轻度的，两组之间的频率相似。GAD-alum治疗诱导GAD特异性免疫应答。结论：GAD-alum可能有助于保存残余的胰岛素分泌在近期发病的1型糖尿病患者，虽然它没有改变胰岛素的需求。（ClinicalTrials.gov编号，NCT 00435981）。
Background: The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age.Methods: We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 microg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied.Results: Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (-0.21 vs. -0.27 nmol per liter [-0.62 vs. -0.81 ng per milliliter], P=0.045), as did stimulated secretion measured as the area under the curve (-0.72 vs. -1.02 nmol per liter per 2 hours [-2.20 vs. -3.08 ng per milliliter per 2 hours], P=0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response.Conclusions: GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.).