Urine Extracellular Vesicles: Non-invasive Biomarkers of Β-cell Function and Novel Therapeutic Agents in Diabetes

Urine Extracellular Vesicles: Non-invasive Biomarkers of Β-cell Function and Novel Therapeutic Agents in Diabetes

Diabetes mellitus is a common chronic disease with a huge socioeconomic burden worldwide. Type 1 Diabetes(T1D) accounts for nearly 95% of diabetes in pediatric age and a lifelong dependence on exogenous insulin. Its diagnosis is based on symptoms and/or autoantibodies, both identified too late to avoid the disease progress. Ideally, children should be screened whilst assymptomatic, when there is endogenous insulin production, but C-peptide and beta-cell function are starting to decline. Early diagnosis would allow interventions capable of preventing disease progress and/or to preserve beta-cell function, ultimately delaying/avoiding insulin dependence. Given their association with pathogenesis of diabetes, Extracellular Vesicles have emerged as potential biomarkers for diagnosis and progression of diabetes. This project proposes the development of a non-invasive biomarker of preclinical T1D, based on miRNA characterization in urine, allowing a timely identification of children that can benefit from preventive therapies and, in the future, to cure T1D.

Inclusion Criteria:

• T1D Group: children diagnosed with T1D, according to internationally defined criteria, with at least one positive pancreatic antibody and under functional insulin.
• Genetic-related group: children without T1D, age- and sex-matched with T1D group, recruited among T1D relatives;
• Control group: children without T1D, age- and sex-matched with T1D group, recruited from general endocrinology clinics, among children without disease or genetic relation with T1D children;

Exclusion Criteria:

• Obesity, according to WHO standards for pediatrics;
• Hypertension, as ≥95th percentile according to International Consensus;
• Other auto-immune diseases;
• Diabetes in the context of syndromic features/secondary to treatments;
• Hypothyroidism, adrenal insufficiency or hypercortisolism;
• Children under somatotropin/oncologic treatment;
• Under medications affecting glucose metabolism