At the Crossroads of Diabetes and Cancer in Children: The Interplay of Genetic Syndromes, Obesity, and Metabolic Dysregulation



Abdolkarimi B ; Doroudian R ; Panahi N ; Rahmati E
Source: Iranian Journal of Blood and Cancer Published:2026

Abstract

Background: Childhood diabetes and cancer have traditionally been viewed as distinct disorders; however, accumulating evidence indicates substantial biological overlap through shared genetic, metabolic, inflammatory, and endocrine pathways. The increasing prevalence of childhood obesity and type 2 diabetes (T2D), together with improved survival among pediatric cancer patients, has intensified interest in the bidirectional relationship between these conditions. Objective: To review current evidence regarding the interplay between diabetes and childhood cancer, with particular emphasis on genetic predisposition syndromes, obesity, insulin resistance, metabolic dysregulation, treatment-related diabetes, and survivorship outcomes. Methods: A comprehensive narrative review of the literature was conducted using major medical databases, including PubMed, Scopus, Embase, and Cochrane Library. Relevant studies addressing childhood diabetes, pediatric malignancies, cancer predisposition syndromes, obesity, insulin resistance, endocrine late effects, and survivorship care were evaluated and synthesized. Results: Emerging evidence demonstrates that obesity, insulin resistance, hyperinsulinemia, chronic inflammation, oxidative stress, and dysregulated insulin-like growth factor-1 (IGF-1) signaling contribute to both metabolic disease and tumorigenesis. Several hereditary cancer predisposition syndromes, including Li–Fraumeni syndrome, Beckwith–Wiedemann syndrome, Constitutional Mismatch Repair Deficiency, Neurofibromatosis type 1, Fanconi anemia, and PTEN hamartoma tumor syndrome, further illustrate the intersection between cancer susceptibility and metabolic dysfunction. Conversely, childhood cancer survivors are at increased risk of developing diabetes because of chemotherapy, corticosteroid exposure, radiotherapy, hematopoietic stem cell transplantation, endocrine organ injury, altered body composition, and persistent inflammation. These metabolic abnormalities may adversely affect treatment response, long-term morbidity, cardiovascular risk, and quality of life. Conclusions: Diabetes and childhood cancer are interconnected through complex genetic and metabolic mechanisms. Recognition of shared pathways and cancer predisposition syndromes may facilitate earlier diagnosis, individualized surveillance, and targeted preventive strategies. Integrating pediatric oncology, endocrinology, genetics, nutrition, and lifestyle interventions is essential to optimize long-term outcomes and survivorship care in this vulnerable population. © 2026, Iranian Pediatric Hematology and Oncology Society. All rights reserved.