Aetiopathogenesis of type 1 diabetes mellitus

Type 1 diabetes mellitus results from a progressive loss of pancreatic beta cells. Environmental factors such as exposure to cow's milk protein and to xins such as nitrosamines are thought to play a pivotal role in the develop ment of type I diabetes by influencing the penetrance of diabetes susceptib ility genes. As one additional environmental factor viruses have long been considered to play a part in type 1 diabetes. The production of cytokines s uch as tumour necrosis factor-alpha (TNF), interleukin-1 beta (II-1) and th e synthesis of nitric oxide (NO) are known to lead to the destruction of be ta cells which results in the development of diabetes. The destruction of p ancreatic beta cells is thought to be a consequence of cytokineinduced prog rammed cell death. The molecular mechanisms and the cell's machinery leadin g to and enhancing apoptosis/programmed cell death have been elucidated. It has become evident that a number of independent and distinct signaling pat hways involving proteins and enzymes such as STATs, tyrosine kinases and sm all G-proteins are all involved in regulating a network of intracellular en zymes, called caspases/interleukin converting enzymes (ICEs) that direct a cell's progression towards death. The production of pro-inflammatory cytoki nes is thought to be a consequence of the disruption of the finely tuned im mune balance of Th1-helper and Th2-helperT lymphocytes. This derangement of the immune system leads to the selective activation of beta-cell-cytotoxic effectorT cells. It is hoped that the knowledge of the aetiopathogenesis o f type I diabetes will help to further develop strategies to prevent and ul timately cure the disease.