The availability of Biobreeding (BB) rats and non-obese diabetic (NOD) mice, TIDM rodent models, has greatly expanded our understanding of possible pathogenic mechanisms. It has recently become possible to compare these results with data obtained in human islets obtained from post-mortem pancreatic specimens through the Pancreas Organ Donor Network (nPOD) and from patients with recent onset DM by endoscopic pancreatic biopsy (9). In addition, epidemiological studies aimed at predicting and preventing T1DM provide a picture of the natural course of the disease. The process of destruction of β-cells is chronic, often beginning in infancy and continuing for many months or years. At the time of the clinical diagnosis of DM1, about +80% of β-cells are destroyed, and the islets are infiltrated with chronic inflammatory mononuclear cells (insulitis), including CD8+ cytotoxic T-cells. Once islet autoimmunity has begun, the progression of islet cell destruction is highly variable, progressing rapidly to clinical diabetes in some patients, while in others the condition remains non-progressive.