Pernille Mogensen - Risk of obesity, insulin resistance, T2D and associated complications during and after treatment for acute lymphoblastic leukaemia in childhood

For the past decades the prognosis for children with acute lymphoblastic leukaemia (ALL) has improved significantly with more than 85% being cured. This in part reflects intensive chemotherapy (amongst others, asparaginase) combined with high doses of steroids. However, the burden of therapy has increased proportionally.

One of the most serious and frequent long-term complications is the development of type 2 diabetes (T2D), which is currently reported in more than 10% of long-term survivors. In addition, physical inactivity during therapy is a risk factor for both obesity, insulin resistance and T2D dependent upon both host and treatment factors. Furthermore, obesity, insulin resistance T2D and associated complications increases the risk of both acute as well as severe life-long co-morbidities including increased mortality.

Since 2008 ALL treatment in the Nordic ALL protocol (NOPHO ALL 2008) has been intensified with the use of higher doses of asparaginase and steroids, which may increase the risk of obesity, insulin resistance and T2D. The aim of the present study is to determine the prevalence of obesity, insulin resistance, T2D and associated complications such as pre-diabetes, hypertension, dyslipidaemia, and Non-alcoholic fatty liver disease (NAFLD) in children diagnosed with ALL as well as long-term survivors of childhood ALL.

Furthermore, we aim to investigate whether physical activity during or after therapy reduce the risk of obesity, insulin resistance and T2D. This study will include a physical exercise intervention study, DEXA- and MR-scans, and a detailed determination of metabolic characteristics including endocrine hormones, pancreatic toxicity and pancreatic activity during and after ALL-therapy.