It is now possible to identify subjects presenting a high risk to develop type 1 (insulin-dependent) diabetes mellitus using immunogenetic and metabolic markers. These markers indicate an ongoing autoimmune process directed toward beta cells which is responsible for insulin deficiency. Combination of several markers like islet cell (ICA) anti-glutamate decarboxylase (GAD) or anti-insulin (IAA) antibodies increases the specificity up to 100% in first degree relatives of diabetic patients. In the general population where 90% of new cases may occur, it is important to increase the specificity and sensitivity of the current markers. Several preventive therapeutic trials have started in high risk relatives using low doses of subcutaneous insulin with a beta cell rest effect or tolerance protocols using oral administration of insulin.