{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:26:34Z","timestamp":1792419994976,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pediatric type 1 diabetes (T1D) disrupts musculoskeletal development during critical windows of growth, puberty, and peak bone mass accrual. Beyond classic micro- and macrovascular complications, accumulating evidence shows a dual burden of diabetic bone disease\u2014reduced bone mineral density, microarchitectural deterioration, and higher fracture risk\u2014and diabetic myopathy, characterized by loss of muscle mass, diminished strength, and metabolic dysfunction. Mechanistically, chronic hyperglycemia, absolute or functional insulin deficiency, and glycemic variability converge to suppress PI3K\u2013AKT\u2013mTOR signaling, activate FoxO-driven atrogenes (atrogin-1, MuRF1), and impair satellite-cell biology; advanced glycation end-products (AGEs) and RAGE signaling stiffen extracellular matrix and promote low-grade inflammation (IL-6, TNF-\u03b1\/IKK\/NF-\u03baB), while oxidative stress and mitochondrial dysfunction further compromise the bone\u2013muscle unit. In vitro, ex vivo, and human studies consistently link these pathways to lower BMD and trabecular\/cortical quality, reduced muscle performance, and increased fractures\u2014associations magnified by poor metabolic control and longer disease duration. Prevention prioritizes tight, stable glycemia, daily physical activity with weight-bearing and progressive resistance training, and optimized nutrition (adequate protein, calcium, vitamin D). Treatment is individualized: supervised exercise-based rehabilitation (including neuromuscular and flexibility training) is the cornerstone of skeletal muscle health. This review provides a comprehensive analysis of the mechanisms underlying the impact of type 1 diabetes on musculoskeletal system. It critically appraises evidence from in vitro studies, animal models, and clinical research in children, it also explores the effects of prevention and treatment.<\/jats:p>","DOI":"10.3390\/cells14201611","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"1611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Muscle-Bone Crosstalk and Metabolic Dysregulation in Children and Young People Affected with Type 1 Diabetes: Mechanisms and Clinical Implications"],"prefix":"10.3390","volume":"14","author":[{"given":"Rossella","family":"Vitale","sequence":"first","affiliation":[{"name":"Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari \u201cAldo Moro\u201d, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Linguiti","sequence":"additional","affiliation":[{"name":"Pediatric Unit \u201cB. Trambusti\u201d, Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Granberg","sequence":"additional","affiliation":[{"name":"Pediatric Unit \u201cB. Trambusti\u201d, Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crescenza","family":"Lattanzio","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari \u201cAldo Moro\u201d, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Giordano","sequence":"additional","affiliation":[{"name":"Pediatric Unit \u201cB. Trambusti\u201d, Department of Interdisciplinary Medicine, University of Bari \u201cAldo Moro\u201d, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-8337","authenticated-orcid":false,"given":"Maria Felicia","family":"Faienza","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari \u201cAldo Moro\u201d, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2017). IDF Diabetes Atlas, International Diabetes Federation. 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