IMMEEDIA

Immunomodulatory Effects of Exercise in Type 1 Diabetes

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 Obiettivo del progetto (Objective)

'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 immunoregulation. 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 dysregulation 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 multicomponent analysis of biological fluids, tissue and cell extracts. Our consortium, through this multi-approach strategy, will reveal how exercise may exert a potent immunomodulatory effect, reducing the autoimmune response that in T1DM attacks and destroys the insulin producing cells.'

Introduzione (Teaser)

Diabetes mellitus, whether type 1 (T1DM) or type 2, is a disease characterised by uncontrolled blood sugar levels due to inadequate insulin production. EU researchers determined how physical activity is beneficial.

Descrizione progetto (Article)

Dysfunction or destruction of insulin-producing beta cells in the pancreas is the main cause for diabetes. Research has indicated that regular and moderate exercise could prevent the onset or worsening of diabetes, an autoimmune condition.

The project IMMEEDIA (Immunomodulatory effects of exercise in type 1 diabetes) was initiated to comprehensively investigate the benefits of exercise for symptom reduction or prevention of T1DM onset. Researchers conducted a large-scale multi-approach study to identify genetic and epigenetic factors predisposing to diabetes as well as suitable biomarkers.

Beta cells are present in the islets of Langerhans in the pancreas. In T1DM patients, beta cell toxicity has been associated with oxidative stress and inflammation as a result of immune system dysfunction. Therefore, testing was done on patients who underwent islet transplantation.

Results revealed that administration of a tailored exercise training programme significantly reduced loss of beta cell function through increased insulin sensitivity that in turn lowers blood sugar levels. Moreover, better immune regulation was apparent.

Studies on non-obese diabetic mice were conducted to gauge the effects of moderate-intensity exercise on the immune system and beta cell function. Results were highly promising, showing improved metabolic capacity and immune modulation.

Project outcomes have provided an evidence-based foundation for using physical exercise as a means to alleviate or prevent diabetes. The results show that exercise is a cornerstone in the prevention, cure and treatment of all-species metabolic disturbances. Besides being cheap and physiological, the risks of over-indulging in exercise are minimal.

Successful demonstration of the protective effects of exercise on immune modulation could also be used to treat other autoimmune diseases such as lupus and rheumatoid arthritis. Besides identifying populations at risk of developing chronic diseases like diabetes, study outcomes could be used to identify interventions that reduce the ensuing socioeconomic burden.