**3.1 Natural history**

The natural history of type 1 diabetes is characterized by an autoimmune destruction of the beta cells in the islands of Langerhans in the pancreas. The autoimmune process has cellular and humoral components, leading to the destruction of the beta cells and a decreased insulin secretion. As beta-cell mass declines, insulin secretion decreases until the available insulin no longer is adequate to maintain normal blood glucose levels. After 70-90% of the beta cells are destroyed, hyperglycemia develops and diabetes may be diagnosed.

The natural history of type 1 diabetes has 4 stages: genetic susceptibility, autoimmune process, pre-diabetes and diabetes.

The rate of beta cell destruction is variable. In some patients years will go by before the onset of diabetes, while other patients may never develop beta cell insufficiency, perhaps due to the regaining of tolerance. Most patients with type 1 diabetes mellitus have one or more susceptible human leukocyte antigen (HLA) class II, and over 90% have beta cell autoantibodies present. The appearance of circulating islet cell autoantibodies is the first detectable sign of this immune process.
