Type 1 diabetes (T1D) is a common chronic disease of childhood associated with a significantly increased risk of micro- and macro-vascular complications, including neuropathy, nephropathy and cardiovascular diseases. The risk of development T1D comorbidities is associated with glycaemic control, a complex mechanism involving biological, physiological environmental factors.

While more than 60 genetic variants were already associated with Glycated hemoglobin (HbA1c) in healthy subjects, very few genes have been identified in T1D individuals. Also, hyperglycaemia could be the cause of epigenetic changes at specific target genes, such as DNA methylation, histone modifications and microRNAs, correlated to accelerated development of diabetes-related complications. Most recently, increasing evidence also suggested that human microbiome may play a crucial role in the onset and progression of T1D and dysbiosis of the gut and oral microbiota was reported as a typical feature of hyperglycaemia.

However, potential differences among poorly and good managed T1D subjects have not been still studied. Also, the exact mechanism by long-term hyperglycaemia's acts in T1D remains poorly understood. Therefore, this project will explore an emerging area of research by the study of possible genetic, epigenetic and environmental biomarkers among T1D subjects with different glycaemic control.

Inclusion Criteria:

• Type 1 diabetes subjects
• Age from 6 to 20 years old
• At least 5 years of duration of disease

Exclusion Criteria:

• Type 1 diabetes subjects incapable of giving valid informed consent or whose parents are incapable of giving valid informed consent.
• Type 1 diabetes subjects for whom it is not possible to collect information on the clinical history, starting from the onset of diabetes
• Subjects with other types of diabetes (i.e. type 2, monogenic diabetes, cystic fibrosis related diabetes)

T1D subjects (children and young adults) attending to several Diabetes Units of Italian and European institutions