Type 2 diabetes, T2D, is a complex disorder with heterogeneous backgrounds. Several disease forms could belong to a context named today as T2D, with a wide spectrum ranging from mono-and/or oligogenic forms, often with an early onset disease, to polygenic ones, due to environment and predisposing genetic background. Our aim is to verify, by a Next Generation Sequencing (NGS) approach, whether Italian patients with early-onset T2D are enriched for mutations in monogenic diabetes genes (MODY and Neonatal Diabetes, ND) than patients with late-onset disease. We will study 4730 T2D patients from 6 Italian T2D study-cohorts. Among these, 300 individuals with age at diagnosis 65 years (late-onset T2D, used as "super controls") will be screened. DNA will be subjected to NGS targeted of 27 MODY- and ND- genes by a custom panel (TSCA Illumina) on MiSeq-Illumina platform. All identified variants will be classified by a filtering/prioritization strategy, based on quality, allele frequency, predicted functional impact and absence in our in-house database. Statistical analyses by burden tests will be carried out to evaluate statistically significant differences in the distribution of MODY-/ND-genes mutations in two study-groups. While tailored, pharmacological treatment is a reality for monogenic diabetes, this is not the case in patients with T2D. Thus, defining the role of MODY and ND-gene mutations in patients with early-onset T2D will help: a) to guide most appropriate clinical and pharmacological treatment for their specific genetic subtype; b) to anticipate long-term clinical evolution and risk of complications; c) to perform genetic counseling in their families. This will be of importance both in children with incidental hyperglycemia and in undiagnosed patients; it could lead also to reclassifying diabetes in patients previously misdiagnosed as having "classical" T2D, with benefits on therapeutic options.