Onset of type I diabetes - A dynamical instability

Type 1 diabetes is a disease characterized by progressive loss of beta-cell function due to an autoimmune reaction affecting the islets of Langerhans. It is now generally accepted that cytokines are implicated in the pathogen esis of autoimmune diseases. Animal studies have shown that interleukin-1 b eta, tumor necrosis factor-alpha, and interferon-gamma affect type 1 diabet es development profoundly It has been suggested that beta-cells are destroy ed by cytokine-induced free radical formation before cytotoxic T-helper (Th )-lymphocytes and/or autoantibody-mediated cytolysis, This hypothesis is kn own as the "Copenhagen model." We introduce a mathematical model encompassi ng the various processes within this framework. The model is expressed in r ate equations describing the changes in numbers of FS-cells, macrophages, a nd Th-lymphocytes. Being concerned with the earliest events, we explore the conditions necessary to maintain self-sustained beta-cell elimination base d on the feedback between immune cells and insulin-producing cells. The mot ivation for this type of analysis becomes clear when we consider the multif actorial and complicated nature of the disease. Indeed, recent research has provided detailed information about the different factors that contribute to the development of the disease, stressing the importance of incorporatin g these findings into a more general picture. A mathematical formalism allo ws for a more comprehensive description of the biological problem and can r eveal nonintuitive properties of the dynamics. Despite the rather complicat ed structure of the equations, our main conclusion is simple: onset of type 1 diabetes is due to a collective, dynamical instability, rather than bein g caused by a single etiological factor.