Füchtenbusch M, Rabl W, Grassl B, Bachmann W, Standl E, Ziegler A G
3rd Medical Department, Hospital München-Schwabing, and Diabetes Research Institute, Munich, Germany.
Diabetologia. 1998 May;41(5):536-41. doi: 10.1007/s001250050943.
The Schwabing Insulin Prophylaxis Trial is a randomised, controlled pilot study designed to examine whether insulin therapy can delay or prevent the clinical onset of Type I diabetes in high risk first degree relatives of people with the disease. First degree relatives of patients with Type I diabetes, who were aged 4 years or more, had an islet cell antibody (ICA) value more than 20 Juvenile Diabetes Foundation Units (JDF-U), a reduced first phase insulin response (FPI) to an i.v. glucose tolerance test less than the 5th centile, and a normal oral glucose tolerance test were eligible for the trial. Between January 1989 and October 1995, 1736 relatives of patients with Type I diabetes were screened for ICA. We identified 64 cases (3.7%) with ICA values more than 20 JDF-U. Of ICA positive relatives, 17 (27%) had a low FPI and were eligible for enrolment. Of these 14 agreed to participate, of whom 7 were randomised to the treatment group and 7 to the control group. In the treatment group, human insulin was administered i.v. by continuous infusion for 7 days, followed by daily s. c. injections for 6 months. Intravenous insulin infusions were repeated every 12 months. In the treatment group 3 of the 7 individuals (follow-up from time of eligibility: 2.3 to 7.1 years) and in the control group 6 of the 7 untreated individuals (1.7 to 7.1 years) developed clinical diabetes. Life table analysis showed that clinical onset of Type I diabetes was delayed in insulin-treated subjects compared with control subjects (means+/-SEM diabetes-free survival: 5.0+/-0.9 years vs 2.3+/-0.7 years, p < 0.03). Insulin levels after i.v. glucose increased in the first year of intervention therapy. Titres of ICA, and antibodies to glutamic acid decarboxylase, and tyrosine phosphatase-like protein IA2 remained unchanged. These data suggest that insulin prophylaxis can delay the onset of overt diabetes in high risk relatives. This is encouraging in view of 1) the continuing American Diabetes Prevention Trial, which is currently testing the effect of parenteral insulin in a large nation-wide study and 2) the initiation of pilot trials to determine whether new antigen-specific intervention is more effective in delaying the clinical onset of Type I diabetes.
施瓦宾胰岛素预防试验是一项随机对照的初步研究，旨在检验胰岛素治疗是否能够延缓或预防I型糖尿病高危一级亲属临床发病。I型糖尿病患者年龄在4岁及以上、胰岛细胞抗体（ICA）值超过20青少年糖尿病基金会单位（JDF-U）、静脉注射葡萄糖耐量试验中第一阶段胰岛素反应（FPI）降低至低于第5百分位数且口服葡萄糖耐量试验正常的一级亲属有资格参加该试验。1989年1月至1995年10月期间，对1736名I型糖尿病患者的亲属进行了ICA筛查。我们确定了64例（3.7%）ICA值超过20 JDF-U的病例。在ICA阳性亲属中，17例（27%）FPI较低且有资格入选。其中14例同意参加，其中7例被随机分配到治疗组，7例被分配到对照组。治疗组中，静脉持续输注人胰岛素7天，随后每日皮下注射6个月。每12个月重复静脉胰岛素输注。治疗组7人中3人（从符合入选标准时起随访：从符合入选标准时起随访：2.3至7.1年），对照组7例未治疗者中有6例（1.7至7.1年）发展为临床糖尿病。寿命表分析显示，与对照组相比，胰岛素治疗组I型糖尿病的临床发病有所延迟（无糖尿病生存均值±标准误：5.0±0.9年 vs 2.3±0.7年，p<0.03）。干预治疗第一年静脉注射葡萄糖后胰岛素水平升高。ICA、谷氨酸脱羧酶抗体和酪氨酸磷酸酶样蛋白IA2的滴度保持不变。这些数据表明，胰岛素预防可延缓高危亲属显性糖尿病的发病。鉴于1）正在进行的美国糖尿病预防试验，该试验目前正在一项全国性大型研究中测试胃肠外胰岛素的效果，以及2）已启动初步试验以确定新的抗原特异性干预措施在延缓I型糖尿病临床发病方面是否更有效，这是令人鼓舞的。
