Glucocorticoids and Insulin Resistance in Children With Acute Lymphoblastic Leukemia

Background. Children treated for acute lymphoblastic leukemia (ALL) are more likely to become overweight. Prolonged exposure to high-dose glucocorticoids may cause insulin resistance and facilitate development of this phenotype. Procedure. Body mass indices (BMI) and insulin resistance (homeostatic model assessment [HOMA]-IR) were prospectively measured among on-(n = 31) and off-therapy participants (n = 29). On-therapy participants were assessed prior to and while on glucocorticoids (5 days of prednisone 40 mg m = 2 or dexamethasone 6 mg m = 2) given as part of routine maintenance chemotherapy, with a subset (n = 10) receiving an intravenous glucose tolerance test (IVGTT) while on glucocorticoids. Results. Baseline HOMA-IR values among on- and off-therapy participants were similar, but among on-therapy participants, HOMA-IR increased significantly with glucocorticoid exposure (median 3.39 vs. 1.26; P < 0.01) with 45.2% of participants having values >4.39 (upper 2.5th percentile among normal weight adolescents). Although baseline HOMA-IR was significantly correlated with current BMI (r = 0.48, P < 0.01), change in HOMA-IR following steroid exposure was not correlated with any demographic or treatment characteristic including current BMI. Among those with IVGTT data, HOMA estimates in general correlated with values derived from a minimal model analysis (r similar to 0.7). Conclusions. High-dose glucocorticoids given as part of routine chemotherapy were associated with a significantly increased insulin resistant state. Given the amount and duration of glucocorticoids children with ALL experience, these physiologic changes could be an important contributor to the development of therapy-related obesity. Pediatr Blood Cancer 2013;60:621-626. (C) 2012 Wiley Periodicals, Inc.