The role of body composition in the development of diabetes mellitus among childhood cancer survivors, and novel intervention strategies to mitigate diabetes risk

The growing population of childhood cancer survivors (CCSs) experiences a large burden of comorbidities, including a markedly increased risk of diabetes mellitus. Among CCSs, prediabetes and diabetes are important risk factors for subsequent cardiovascular disease, which is a leading cause of premature death in this patient population. The mechanisms underlying their development are multifactorial, and may differ from those in the general population. Emerging evidence from preclinical and clinical studies suggests that treatment-related alterations in body composition, specifically sarcopenic obesity, the aging-related loss of skeletal muscle mass with a simultaneous increase in adipose tissue mass, are a key contributory factor. Both skeletal muscle and adipose tissue are important endocrine organs involved in maintaining glucose homeostasis, with tissue crosstalk that can be disrupted by chemotherapy and radiation exposures. CCSs are particularly vulnerable to these effects as a result of receipt of cancer treatment during key periods of physiologic development, when organs are still maturing and there is peak muscle growth. Lifestyle modifications, which are a first-line intervention to improve muscle health and mitigate diabetes risk, have historically been difficult to implement long term. This review summarizes the current understanding of the impact of cancer and its treatment on muscle and adipose tissue by identifying important knowledge gaps and drawing on translational insights from preclinical models. Furthermore, it highlights opportunities to leverage contemporary digital care platforms to improve the early detection of diabetes and facilitate meaningful, sustainable lifestyle interventions to improve muscle health and decrease diabetes risk in the growing, at-risk population of CCSs.