title: Glucocorticoids and insulin resistance in children with acute lymphoblastic leukemia.
abstract: 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.
  
  
  METHODS
  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 ~ 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.
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA. ericchow@u.washington.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chow
authors.forename: Catherine
authors.initials: C
authors.lastname: Pihoker
authors.forename: Debra L
authors.initials: DL
authors.lastname: Friedman
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: McCune
authors.forename: Claire
authors.initials: C
authors.lastname: Wharton
authors.forename: Christian L
authors.initials: CL
authors.lastname: Roth
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced* / Q000453:epidemiology; D007333:Insulin Resistance; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids