Keymeulen B
UZ Brussel and Diabetes Research Center, VUB, Laarbeeklaan 103, B 1090 Brussel.
Verh K Acad Geneeskd Belg. 2008;70(2):85-103.
Type 1 diabetes is caused by an immune mediated destruction of the insulin-secreting beta cells in the pancreas. The disease can become clinically apparent at any age. At clinical diagnosis, there is invariably some residual beta cell function. Recent studies--including one mainly conducted in Belgium--have provided proof of principle that short-term humanized anti-T-cell antibody treatment is able to preserve residual beta cell function for at least 18 months in adult type 1 diabetic patients with a recent clinical onset of disease. The effect of anti-T-cell antibody treatment is more pronounced among patients with initial higher residual beta-cell function. The resultant stabilizing effect on metabolic control is expected to delay chronic complications and avoid hypoglycemia in these patients. With a similar goal in mind, non-uremic C-peptide negative type 1 diabetic patients are offered beta cell transplantation. During the last years the one year survival of these grafts under immune suppression with Anti-Thymocyte-Globulin, tacrolimus and mycophenolate mofetil exceeds 80% with virtually no cases of primary non-function. Widespread application will however only occur if ways are found to induce operational graft tolerance and the shortage of viable human donor cells can be overcome. Both islet xenotransplantation and stem cell therapy provide possible strategies to solve this problem and represent areas of intense investigation. The ultimate goal is prevention of clinical disease. Studies by the Belgian Diabetes Registry and others in first degree family members of type 1 diabetic patients have refined identification of individuals at very high risk of hyperglycemia so that new immunological treatments can be tested in the prediabetic phase.
1型糖尿病是由免疫介导的胰腺中分泌胰岛素的β细胞破坏所致。该疾病在任何年龄都可能在临床上显现出来。在临床诊断时，总会存在一些残余的β细胞功能。近期的研究——包括一项主要在比利时开展的研究——已提供了原理证明，即短期人源化抗T细胞抗体治疗能够使近期临床发病的成年1型糖尿病患者的残余β细胞功能至少维持18个月。抗T细胞抗体治疗在初始残余β细胞功能较高的患者中效果更为显著。预计由此对代谢控制产生的稳定作用可延缓这些患者的慢性并发症并避免低血糖。出于类似目的，对于非尿毒症性C肽阴性的1型糖尿病患者，会提供β细胞移植。在过去几年中，在使用抗胸腺细胞球蛋白、他克莫司和霉酚酸酯进行免疫抑制的情况下，这些移植物的一年存活率超过80%，几乎没有原发性无功能的病例。然而，只有当找到诱导手术移植耐受的方法并且能够克服 viable 人类供体细胞短缺的问题时，才会广泛应用。胰岛异种移植和干细胞疗法都提供了解决这一问题的可能策略，并且是深入研究的领域。最终目标是预防临床疾病。比利时糖尿病登记处及其他机构对1型糖尿病患者的一级家庭成员进行的研究，已完善了对处于高血糖极高风险个体的识别，以便能够在糖尿病前期阶段对新的免疫治疗方法进行测试。
