Kobayashi Tetsuro, Maruyama Taro, Shimada Akira, Kasuga Akira, Kanatsuka Azuma, Takei Izumi, Tanaka Shoichiro, Yokoyama Junichi
Department of Endocrinology and Metabolism, Toranomon Hospital, Okinaka Memorial Institute for Medical Research, Tokyo, 105-8470, Japan.
Ann N Y Acad Sci. 2002 Apr;958:117-30. doi: 10.1111/j.1749-6632.2002.tb02954.x.
Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is characterized by (1) late age of onset, with initial features of NIDDM and subsequent progression to insulin-dependent stage; (2) high predictive value of autoantibodies against glutamic acid decarboxylase (GADAb) and islet cell antibodies (ICA) for progression of beta cell failure; (3) less predominant T cell response, which may attack and eventually destroy beta-cells in affected pancreas. These findings may suggest a rationale for intervention to prevent slowly progressive beta cell dysfunction in this type of diabetes. We identified three independent risk factors for progression of beta cell failure in SPIDDM: (1) sulfonylurea treatment; (2) ICA-positive periods; and (3) initial body weight. We hypothesized that removal of the risk factors for further progression of beta cell dysfunction will have beneficial effects on intervention strategy in treating SPIDDM. In our pilot study, we used a small dose of insulin instead of sulfonylurea in the early stage of treatment of patients with SPIDDM. Insulin-treated SPIDDM patients had a sustained C peptide response (CPR), while most of sulfonylurea-treated patients progressed to an insulin-dependent state. We organized a randomized multicenter clinical trial to study early treatment to prevent the progression of beta cell dysfunction in SPIDDM (the Tokyo Study). It was demonstrated that early intervention with insulin therapy is an effective treatment modality in the early stage of SPIDDM patients who had preserved beta cell function at entry (integrated value of serum C peptide values at 0, 30, 60, 90, and 120 minutes; Sigma CPR >or= 10 ng/mL) and high GADAb (>10 U/mL). Preventive insulin treatment was ineffective in the patients who had diminished insulin reserve at entry (Sigma CPR < 10 ng/mL). Insulin intervention to preserve beta cell dysfunction in SPIDDM is effective and safe in patients with preserved beta cell function and high GADAb titers at the initiation of insulin.
缓慢进展型胰岛素依赖型（1型）糖尿病（SPIDDM）的特征为：（1）发病年龄较晚，起初具有非胰岛素依赖型糖尿病的特征，随后进展至胰岛素依赖阶段；（2）谷氨酸脱羧酶自身抗体（GADAb）和胰岛细胞抗体（ICA）对β细胞功能衰竭进展具有较高预测价值；（3）T细胞反应不占主导，可能攻击并最终破坏受累胰腺中的β细胞。这些发现可能为干预以预防此类糖尿病中缓慢进展的β细胞功能障碍提供了理论依据。我们确定了SPIDDM中β细胞功能衰竭进展的三个独立危险因素：（1）磺脲类药物治疗；（2）ICA阳性期；（3）初始体重。我们假设消除β细胞功能障碍进一步进展的危险因素将对SPIDDM的干预策略产生有益影响。在我们的初步研究中，我们在SPIDDM患者治疗早期使用小剂量胰岛素而非磺脲类药物。胰岛素治疗的SPIDDM患者具有持续的C肽反应（CPR），而大多数磺脲类药物治疗的患者进展至胰岛素依赖状态。我们组织了一项随机多中心临床试验，以研究早期治疗预防SPIDDM中β细胞功能障碍的进展（东京研究）。结果表明，对于入组时β细胞功能尚存（0、30、60、90和120分钟时血清C肽值的积分值；Sigma CPR≥10 ng/mL）且GADAb较高（>10 U/mL）的SPIDDM患者，早期胰岛素治疗干预是一种有效的治疗方式。预防性胰岛素治疗对入组时胰岛素储备减少（Sigma CPR<10 ng/mL）的患者无效。在胰岛素起始治疗时β细胞功能尚存且GADAb滴度较高的患者中，胰岛素干预以保留SPIDDM中的β细胞功能是有效且安全的。
