Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden.
N Engl J Med. 2012 Feb 2;366(5):433-42. doi: 10.1056/NEJMoa1107096.
The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.
We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.
The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.
Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).
谷氨酸脱羧酶 65kDa 同工型（GAD65）是 1 型糖尿病的主要自身抗原。我们假设，明矾制剂谷氨酸脱羧酶 65（GAD-明矾）可以在发病不久的 1 型糖尿病患者中保护β细胞功能。
我们研究了 334 名年龄在 10 至 20 岁之间的 1 型糖尿病患者，这些患者空腹 C 肽水平大于 0.3ng/ml（0.1nmol/L），且血清 GAD65 自身抗体可检测到。在诊断后 3 个月内，患者被随机分配接受三种研究治疗之一：4 剂 GAD-明矾、2 剂 GAD-明矾后 2 剂安慰剂或 4 剂安慰剂。主要结局是在基线访视和 15 个月访视之间，受刺激的血清 C 肽水平（混合餐耐量试验后）的变化。次要结局包括糖化血红蛋白水平、平均每日胰岛素剂量、低血糖发生率以及空腹和最大刺激 C 肽水平。
所有研究组的受刺激 C 肽水平下降程度相似，15 个月时的主要结局在联合用药组和安慰剂组之间没有显著差异（P=0.10）。与安慰剂相比，使用 GAD-明矾并未影响胰岛素剂量、糖化血红蛋白水平或低血糖发生率。三组不良反应均不常见且轻微，无显著差异。
在 15 个月期间，GAD-明矾治疗并未显著减少受刺激 C 肽的丢失或改善临床结局。（由 Diamyd Medical 和瑞典儿童糖尿病基金会资助；ClinicalTrials.gov 编号，NCT00723411）。
