{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T20:09:05Z","timestamp":1782331745366,"version":"3.54.5"},"reference-count":113,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T00:00:00Z","timestamp":1677974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the \u03b2-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered \u03b2-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue \u03b2-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before.<\/jats:p>","DOI":"10.3390\/children10030516","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T04:29:58Z","timestamp":1678076998000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["From Metabolic Syndrome to Type 2 Diabetes in Youth"],"prefix":"10.3390","volume":"10","author":[{"given":"Dario","family":"Iafusco","sequence":"first","affiliation":[{"name":"Department of Woman, Child and General and Specialistic Surgery, Regional Center of Pediatric Diabetes, University of Campania \u201cL. Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-7148","authenticated-orcid":false,"given":"Roberto","family":"Franceschi","sequence":"additional","affiliation":[{"name":"Pediatric Department, S. Chiara Hospital of Trento, APSS, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8921-2012","authenticated-orcid":false,"given":"Alice","family":"Maguolo","sequence":"additional","affiliation":[{"name":"Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Guercio Nuzio","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Women\u2019s and Children\u2019s Health, S. Maria della Speranza Hospital of Battipaglia, 84091 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Crin\u00f2","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases and Congenital Defects\u2014Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-0012","authenticated-orcid":false,"given":"Maurizio","family":"Delvecchio","sequence":"additional","affiliation":[{"name":"Metabolic Disorders and Diabetes Unit, \u201cGiovanni XXIII\u201d Children\u2019s Hospital, A.O.U. Policlinico di Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-7872","authenticated-orcid":false,"given":"Lorenzo","family":"Iughetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Mothers, Children and Adults, Post Graduate School of Pediatrics, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-4404","authenticated-orcid":false,"given":"Claudio","family":"Maffeis","sequence":"additional","affiliation":[{"name":"Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-5974","authenticated-orcid":false,"given":"Valeria","family":"Calcaterra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Department, \u201cV. Buzzi\u201d Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-975X","authenticated-orcid":false,"given":"Melania","family":"Manco","sequence":"additional","affiliation":[{"name":"Preventive and Predictive Medicine Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.21037\/tp.2017.10.02","article-title":"Metabolic syndrome in children and adolescents","volume":"6","author":"Raman","year":"2017","journal-title":"Transl. 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