Phillips Brett E, Giannoukakis Nick, Trucco Massimo
Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, PA, USA.
Pediatr Endocrinol Rev. 2008 Jun;5(4):873-9.
Diabetes is a state of imbalance in insulin secretion and tissue sensitivity resulting in hyperglycemia and a host of other metabolic changes. Increased patient morbidity and mortality are caused in part by diabetic complications that include cardio-vascular complications, retinopathy, neuropathy, and nephropathy (1). The early onset of disease in type 1 diabetes mellitus increases the effects of these complications since the risk of development increases with disease duration. Clinical agents are currently available for type 2 diabetic patients to increase both secretion and sensitivity to insulin. These compounds are ineffective in type 1 diabetic patients due to the destruction of the insulin producing beta cells in the pancreatic islets of Langerhans, making type 1 and non-responsive type 2 diabetic patients dependent on insulin replacement therapy. Intensive insulin treatment delays onset of these complications, but does not eliminate them (1). Insulin replacement therapy is not a cure for type 1 diabetes; to establish a cure, the destruction of the beta cells themselves must be directly addressed. Here we will focus on immunoregulatory techniques to prevent beta cell loss due to the autoimmunity found in type 1 diabetes mellitus.
糖尿病是一种胰岛素分泌与组织敏感性失衡的状态,会导致高血糖以及一系列其他代谢变化。糖尿病并发症(包括心血管并发症、视网膜病变、神经病变和肾病)在一定程度上导致了患者发病率和死亡率的增加(1)。1型糖尿病的早期发病会加剧这些并发症的影响,因为并发症的发生风险会随着病程的延长而增加。目前有临床药物可用于2型糖尿病患者,以增加胰岛素分泌和提高对胰岛素的敏感性。由于1型糖尿病患者胰岛中产生胰岛素的β细胞遭到破坏,这些化合物对1型糖尿病患者无效,这使得1型糖尿病患者和无反应的2型糖尿病患者依赖胰岛素替代疗法。强化胰岛素治疗可延缓这些并发症的发生,但无法消除它们(1)。胰岛素替代疗法并不能治愈1型糖尿病;要实现治愈,必须直接解决β细胞自身的破坏问题。在此,我们将重点关注免疫调节技术,以防止1型糖尿病中因自身免疫导致的β细胞损失。