ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Pediatr Blood Cancer. 2018; 65(11): e27304.

Observational studies in large cohorts of cancer survivors have reported that cancer survivors exposed to abdominal radiation have an increased risk of both insulin-dependent and non-insulin-dependent diabetes mellitus, with a prolonged latency between radiation exposure and diabetes onset. The irradiation of the pancreatic tail, where insulin-producing beta-cells are concentrated, has been implicated as the main risk factor.

This cross-sectional study analysed a relatively small group (40 subjects) of childhood cancer survivors treated with abdominal radiotherapy (aRT) at age ≤21 years. In this study, 70% (n=28) of the enrolled patients were survivors of neuroblastoma treated with aRT; 26/28 patients had stage 4 disease, receiving aggressive multimodal treatment. The enrolled patients underwent oral glucose tolerance test (OGTT) and assessment of diabetes-related autoantibodies [autoantibodies against insulin (IAA), glutamic acid decarboxylase (GAD-65), and islet antigen-2 (IA-2)]. Impaired glucose tolerance was found more prevalent in patients previously treated with aRT, independently of obesity and in the absence of pancreatic autoimmunity. Two patients showed isolated GAD65 positivity, associated with normal glucose tolerance. Three of the four individuals with impaired fasting glucose showed also insulin resistance, as measured by HOMA-IR. Four additional subjects with normal glucose tolerance were insulin resistant. No participant had absolute insulinopenia.

The correlation between aRT and diabetes has been already described, with discordant data about the dose–response relationship. A few previous studies had analyzed specific markers of pancreatic autoimmunity leading to beta-cell damage and type 1 diabetes in childhood cancer survivors. Overall, these auto-antibodies were not found in the analyzed subjects. (1–3), confirming that pancreatic autoimmunity is not implicated in the pathogenesis of diabetes mellitus in cancer survivors. Despite the established association between radiation dose to the pancreatic tail and diabetes risk, this study shows that autoimmunity and absolute insulinopenia, as might be expected after direct radiation-induced damage to the insulin producing beta-cells, does not seem to play a role in the pathophysiology of glucose metabolism derangement. Abdominal therapeutic irradiation has been associated with specific body composition changes (fat redistribution with central and visceral fat accumulation) and the various components of the metabolic syndrome, which were not systematically assessed in this study. Further research into alternative pathways leading to diabetes after aRT is needed.

References: 1. Mohn A, Di Marzio D, De Berardiniis A, Di Marzio A, Capanna R, Fioritoni G, Chiarelli F. Long-term follow-up of children treated for acute lymphoblastic leukemia and the recovery of beta-cell function. Haematologica 2006; 9: 1424–1425.

2. Davies JH, Evans BA, Jenney ME, Gregory JW. In vitro effects of combination chemotherapy on osteoblasts: Implications for osteopenia in childhood malignancy. Bone 2002; 31: 319–326.

3. D’Annunzio G, Bonetti F, Locatelli F, Pistorio A, Lorini R. Insulin resistance in children and adolescents after bone marrow transplant for haematological malignancies. Haematologica 2006; 91(12 Suppl).