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Glucocorticoids and insulin resistance in children with acute lymphoblastic leukemia

Authors

  • Eric J. Chow MD, MPH,

    Corresponding author
    1. Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington
    2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    • Fred Hutchinson Cancer Research Center, Box 19024, M4-C308, Seattle, WA 98109.
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  • Catherine Pihoker MD,

    1. Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington
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  • Debra L. Friedman MD, MS,

    1. Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee
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  • Stephanie J. Lee MD, MPH,

    1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
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  • Jeannine S. McCune PharmD,

    1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Pharmacy, University of Washington, Seattle, Washington
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  • Claire Wharton BS,

    1. Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington
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  • Christian L. Roth MD,

    1. Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington
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  • K. Scott Baker MD, MS

    1. Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington
    2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
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  • Conflict of interest: Nothing to declare

  • Financial disclosures: none

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.

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 ∼ 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. © 2012 Wiley Periodicals, Inc.

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