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Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics

Abstract

Introduction

Medication induced diabetes (MID) during induction therapy (MIDi) in patients with acute lymphoblastic leukemia (ALL) is not well characterized in children, with recent studies yielding conflicting results.

Purpose

The purpose of the study was to describe the prevalence of MIDi and risk factors for its development.

Methods

We retrospectively gathered demographic, disease course and treatment data on 363 patients aged 1 to 17.9 years diagnosed with ALL at a pediatric tertiary care hospital between 1998 and 2005. MIDi was defined as blood glucose ≥200 mg/dL (11.1 mmol/L) on at least 2 separate days during induction.

Results

Fifty-seven subjects (15.7%) developed MIDi during the study period. Patients ≥10 years were more likely to develop MIDi than those <10 years (odds ratio [OR] 9.6, 95% confidence interval [CI] 5.1–17.8). BMI percentile among those with MIDi (mean ± SD 58.2 ± 31.0) did not differ from those without MIDi (52.2 ± 32.0, P = 0.429). The presence of Trisomy 21 (OR 3.6, 95% CI 1.1–11.4, P = 0.030) and CNS involvement at diagnosis (OR 3.8, 95% CI 1.4–10.1, P = 0.009) were associated with an increased risk of MIDi. After adjustment for potential confounding variables, age ≥10 years and the presence of CNS disease at diagnosis remained significantly associated with MIDi.

Conclusions

Older age and CNS involvement at diagnosis increase the risk of MIDi. In contrast to previous studies, higher BMI was not associated with MIDi in our population.

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References

  1. Howard SC, Pui CH (2002) Endocrine complications in pediatric patients with acute lymphoblastic leukemia. Blood Rev 16:225–243

    PubMed  Article  Google Scholar 

  2. Ho JPD (2004) Secondary diabetes in children. Can J Diabet 28:400–405

    Google Scholar 

  3. Hoffmeister PA, Storer BE, Sanders JE (2004) Diabetes mellitus in long-term survivors of pediatric hematopoietic cell transplantation. J Pediatr Hematol/Oncol 26:81–90

    Article  Google Scholar 

  4. Mohn A, Di Marzio A, Capanna R, Fioritoni G, Chiarelli F (2004) Persistence of impaired pancreatic beta-cell function in children treated for acute lymphoblastic leukaemia. Lancet 363:127–128

    PubMed  Article  CAS  Google Scholar 

  5. Hjelmesaeth J, Midtvedt K, Jenssen T, Hartmann A (2001) Insulin resistance after renal transplantation: impact of immunosuppressive and antihypertensive therapy [see comment]. Diabetes Care 24:2121–2126

    PubMed  Article  CAS  Google Scholar 

  6. Fischman D, Nookala VK (2008) Cystic fibrosis-related diabetes mellitus: etiology, evaluation, and management. Endocr Pract 14:1169–1179

    PubMed  Google Scholar 

  7. Joss N, Staatz CE, Thomson AH, Jardine AG (2007) Predictors of new onset diabetes after renal transplantation. Clin Transplant 21:136–143

    PubMed  Article  Google Scholar 

  8. Marchetti P (2004) New-onset diabetes after transplantation. J Heart Lung Transplant 23:S194–S201

    PubMed  Article  Google Scholar 

  9. Mi TDC, Rego LO, Lima AS (2003) Post-liver transplant obesity and diabetes. Curr Opin Clin Nutr Metab Care 6:457–460

    Google Scholar 

  10. Baillargeon J, Langevin AM, Mullins J, Ferry RJ Jr, DeAngulo G, Thomas PJ, Estrada J, Pitney A, Pollock BH (2005) Transient hyperglycemia in Hispanic children with acute lymphoblastic leukemia. Pediatr Blood Cancer 45:960–963

    PubMed  Article  Google Scholar 

  11. Lowas SR, Marks D, Malempati S (2009) Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer 52:814–818

    PubMed  Article  Google Scholar 

  12. Roberson JR, Spraker HL, Shelso J, Zhou Y, Inaba H, Metzger ML, Rubnitz JE, Ribeiro RC, Sandlund JT, Jeha S, Pui CH, Howard SC (2009) Clinical consequences of hyperglycemia during remission induction therapy for pediatric acute lymphoblastic leukemia. Leukemia 23:245–250

    PubMed  Article  CAS  Google Scholar 

  13. Sonabend RY, McKay SV, Okcu MF, Yan J, Haymond MW, Margolin JF (2009) Hyperglycemia during induction therapy is associated with poorer survival in children with acute lymphocytic leukemia. J Pediatr 155:73–78

    PubMed  Article  Google Scholar 

  14. Sperling MA (2002) The adrenal cortex. In: Pediatric endocrinology, 2nd edn. Saunders, Philadelphia; 413

  15. Silverman LB (2007) Acute lymphoblastic leukemia in infancy. Pediatr Blood Cancer 49:1070–1073

    PubMed  Article  Google Scholar 

  16. Pui CH, Burghen GA, Bowman WP, Aur RJ (1981) Risk factors for hyperglycemia in children with leukemia receiving l-asparaginase and prednisone. J Pediatr 99:46–50

    PubMed  Article  CAS  Google Scholar 

  17. Association AD (2006) Diagnosis and classification of diabetes mellitus. Diabetes Care 29(Suppl 1):S43–S48

    Google Scholar 

  18. 2000 Center for Disease Control growth charts—body mass index percentiles and SDS. www.cdc.gov/growthcharts

  19. Smith M, Arthur D, Camitta B et al (1996) Uniform approach to classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 14(1):18–2420

    PubMed  CAS  Google Scholar 

  20. Amed S, Dean HJ, Panagiotopoulos C, Sellers EA, Hadjiyanakis S, Laubscher TA, Dannenbaum D, Shah BR, Booth GL, Hamilton JK (2010) Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study. Diabetes Care 33(4):786–791

    PubMed  Article  Google Scholar 

  21. Amed S, Dean H, Sellers EA, Panagiotopoulos C, Shah BR, Booth GL, Laubscher TA, Dannenbaum D, Hadjiyannakis S, Hamilton JK (2011). Risk factors for medication-induced diabetes and type 2 diabetes. J Pediatr. [Epub ahead of print]

  22. Tjepkema M (2004) Adult obesity in Canada: measured height and weight. In: Nutrition: findings from the Canadian Community Health Survey. Statistics Canada, Ottawa.

  23. Weiser MA, Cabanillas ME, Konopleva M, Thomas DA, Pierce SA, Escalante CP et al (2004) Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen [see comment]. Cancer 100(6):1179–1185

    PubMed  Article  CAS  Google Scholar 

  24. Pieters R, Carroll WL (2008) Biology and treatment of acute lymphoblastic leukemia. Pediatr Clin North Am 55(1):1–20, ix

    PubMed  Article  Google Scholar 

  25. Vrooman LM, Silverman LB (2009) Childhood acute lymphoblastic leukemia: update on prognostic factors. Curr Opin Pediatr 21(1):1–8

    PubMed  Article  Google Scholar 

  26. Truong TH, Beyene J, Hitzler J, Abla O, Maloney AM, Weitzman S, Sung L (2007) Features at presentation predict children with acute lymphoblastic leukemia at low risk for tumor lysis syndrome. Cancer 110(8):1832–1839

    PubMed  Article  Google Scholar 

  27. Afzal S, Ethier MC, Dupuis LL, Tang L, Punnett AS, Richardson SE, Allen U, Abla O, Sung L (2009) Risk factors for infection-related outcomes during induction therapy for childhood acute lymphoblastic leukemia. Pediatr Infect Dis J 28(12):1064–1068

    PubMed  Article  Google Scholar 

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The authors have no conflict of interest to declare.

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Correspondence to Dror Koltin.

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Koltin, D., Sung, L., Naqvi, A. et al. Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics. Support Care Cancer 20, 2009–2015 (2012). https://doi.org/10.1007/s00520-011-1307-5

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  • DOI: https://doi.org/10.1007/s00520-011-1307-5

Keywords

  • Hypergylcemia
  • ALL
  • Induction
  • Pediatric
  • Glucocorticoids
  • Asparaginase