The Finnish type 1 Diabetes Prediction and Prevention (DIPP) project ( 6) started in 1994 and follows newborn infants with increased genetic risk in close intervals for up to 10 years. A total of 1,642 offspring have been recruited at birth and participated in the follow-up. By today, it represents the longest-running prospective study from birth examining the risks for islet autoimmunity and type 1 diabetes. The German BABYDIAB study commenced in 1989 to prospectively follow islet autoantibody and diabetes development in newborn offspring of parents with type 1 diabetes ( 5). PROSPECTIVE STUDIES FROM BIRTH INVESTIGATING THE NATURAL HISTORY OF TYPE 1 DIABETES
In this article, we will present our current view on the natural history of islet autoimmunity, factors that influence its appearance and progression, and characteristics that are associated with the development of type 1 diabetes. Information gained from all these studies in pre-diabetes will determine how we can predict type 1 diabetes, identify individuals who may benefit from intervention to halt autoimmunity, and ultimately determine how we may prevent type 1 diabetes. Based on this principle, a multi-center study called The Environmental Determinants of Diabetes in the Young (TEDDY) has been launched to examine what environmental factors shape the autoimmunity that leads to type 1 diabetes ( 9). Using these autoantibodies, it is possible to trace events that occur during the preclinical phase of type 1 diabetes. The relevant islet autoantibodies identified so far are autoantibodies to insulin (IAAs), the 65-kDa isoform of GAD (autoantibody to GAD ), and the protein tyrosine phosphatase–related molecules IA-2 (autoantibody to IA-2 ) and IA-2β ( 1). We now know when islet autoantibodies first appear in life, some of the genetic factors influencing their development, and which characteristics of islet autoantibodies are most associated with progression to type 1 diabetes.
Findings from these studies have significantly contributed to our current understanding of the pathogenesis of childhood diabetes. Over the last 15 years, several groups have initiated prospective studies from birth examining the development of islet autoimmunity and diabetes ( 5– 8), providing an opportunity to test such theoretical models in patients developing type 1 diabetes. The model of the natural history of type 1 diabetes suggests stages that commence with a genetic susceptibility, autoimmunity without clinical disease, and finally clinical diabetes ( 4).