Diabetes is a major metabolic disease with huge costs for healthcare system throughout the EU and worldwide. Type 1 Diabetes (T1DM) is a chronic condition in which pancreas produces little or no insulin, believed to result from a disorder of immuno-regulation. For decades it has been known that regular aerobic exercise improves insulin sensitivity in diabetic patients, reducing insulin requirements. Traditionally, physical exercise has been promoted in type 2 diabetes, where insulin action is deficient in the context of insulin resistance and/or inappropriate insulin secretion. However, even in T1DM, in the dys-regulation of immune system function, beta-cell toxicity is mediated by a complex interplay between oxidative stress and inflammation, for which exercise could be protective. Preliminary observations in fact indicate that regularly exercising T1DM-subjects have lower autoimmunity markers at an early stage of the disease. We want to ascertain the effect of moderate regular exercise as the most convenient measure to avoid the onset/worsening of T1DM. To verify whether exercise is capable of countering the T1DM-autoimmune process directed against beta-cells of the pancreatic islets, a multi-centric study will include: a) administration of a tailored exercise training program in different cohorts of T1DM-subjects; b) in-vivo animal experiments in which gain/loss-function models will be challenged with exercise; c) cell studies to analyse the exercise effects on signal transduction pathways and cytokine responses; d) metabolic profiling and metabolomic studies concerning the multi-component analysis of biological fluids, tissue and cell extracts. Our consortium, through this multi-approach strategy, will reveal how exercise may exert a potent immuno-modulatory effect, reducing the autoimmune response that in T1DM attacks and destroys the insulin producing cells.