Immunogenetics of Type 1 Diabetes

Type 1 diabetes (T1D), also known as Insulin dependent diabetes mellitus (IDDM) is an incurable multi-factorial autoimmune disorder. The disease is characterized by the loss of insulin producing beta cells of the pancreas resulting in abnormal metabolism of glucose which may lead to ketoacidosis and several other complications like retinopathy, nephropathy and even cardio-vascular diseases and pre-mature deaths (Pociot & Mcdermott, 2002). World-wide disease affects 1 in 300-400 children (Todd, 1995). Population based data from South India shows the incidence of T1D for four year period to be 10.5/100,000/ year (Ramachandran et al., 1996). Similar prevalence of type 1 diabetes has been observed in North India. A study from district of Karnal in North India reported the prevalence to be 10.20/100,000 population, with a higher prevalence in urban (26.6/100,000) as compared to rural areas (4.27/100,000) (Kalra et al. 2010). T1D develops as a result of complex interaction of many genetic and environmental factors leading to autoimmune destruction of the insulin producing pancreatic beta cells. While 20 genomic intervals have been implicated for the manifestation of the disease (Pociot & Mcdermott, 2002), role of an intricate network of the products of these genes cannot be ruled out. However, unravelling different factors involved and how they interact in integrated networks is like solving a jig-saw puzzle which is the aim of our studies. Basic problem with T1D patients is that by the time they first report to the physician, most of their pancreatic beta cells are already destroyed which leaves the clinicain with no option but to give daily insulin injections. So, there is a need to identify the prediabetics before the onset of the disease and device ways to inhibit autoimmunity in them. Following sections will show the work done in our laboratory to understand the intricate networks in which the genes involved in immune responses interact and their implications.