Type 1 Diabetes Genetics

Type 1 diabetes (T1D) arises as a result of autoimmune destruction of cells in the pancreatic islets that are the sole producers of insulin.  As these cells are lost, the affected individual loses the ability to maintain glucose levels in the normal physiologic range and becomes diabetic.  While insulin replacement therapy is life-saving, prolonged diabetes, even if well managed, can be associated with severe complications that leading to kidney failure, blindness, or amputation.  T1D is a complex disease that arises from the contributions of both genetic and environmental risk factors which are still largely undefined.  For more than 20 years, our studies of T1D have focused on defining the genetic risk factors that contribute to susceptibility to this disorder with the goals of better understanding the underlying pathology, and facilitating preventive approaches through early diagnosis and novel therapies.  As a result of genome-wide association studies there are now more than 40 regions of the genome known to harbor genetic loci that increase risk for T1D.  Our current studies are directed towards identifying the causative variants in these chromosomal regions, characterizing the effects of these variants on the relevant genes, and understanding how variation in the expression of these genes or the structure of their protein products impacts T1D pathology.