Skip to main content
SpringerLink
Log in

Risk factors for diabetes mellitus and impaired glucose tolerance following allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Long-term surviving recipients of allogeneic hematopoietic stem cell transplantation (HSCT) often suffer from diabetes mellitus (DM). We sought to identify risk factors for the development of post-transplant DM and impaired glucose tolerance (IGT) in pediatric HSCT patients. Glucose tolerance statuses were evaluated in 22 patients aged 6.3–21.8 years who had received allogeneic HSCT between the ages of 0.8–13.5 years. Five patients were diagnosed as having type 2 DM, and treated with insulin or oral hypoglycemic agents. Five patients were included in the IGT group, and the remaining 12 children were in the normal glucose tolerance (NGT) group. The cumulative incidence of DM plus IGT was 11.6 % at 5 years and 69.3 % at 10 years. None of the patients were obese/overweight and none had a family history of DM. There were no significant differences in serum levels of leptin and adiponectin between the DM + IGT and the NGT groups. An average preprandial glucose levels in the DM + IGT group were significantly higher than those in the NGT group from preparative conditioning to 60 days after HSCT. In multivariate analysis, an age of ≥6 years at the time of HSCT was significantly associated with the development of DM + IGT. Additionally, careful follow-up is necessary, even for NGT patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Horibe K, Saito AM, Takimoto T, Tsuchida M, Manabe A, Shima M, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006–2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013;98:74–88.

    Article  PubMed  Google Scholar 

  2. Cohen A, Békássy AN, Gaiero A, Faraci M, Zecca S, Tichelli A, et al. Endocrinological late complications after hematopoietic SCT in children. Bone Marrow Transpl. 2008;41:S43–8.

    Article  CAS  Google Scholar 

  3. Ishida Y, Honda M, Ozono S, Okamura J, Asami K, Maeda N, et al. Late effects and quality of life of childhood cancer survivors: part 1. Impact of stem cell transplantation. Int J Hematol. 2010;91:865–76.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. Taskinen M, Saarinen-Pihkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet. 2000;356:993–7.

    Article  PubMed  CAS  Google Scholar 

  6. Bonanomi S, Gaiero A, Masera N, Rovelli A, Uderzo C, Fichera G, et al. Distinctive characteristics of diabetes mellitus after hematopoietic cell transplantation during childhood. Pediatr Transpl. 2006;10:461–5.

    Article  Google Scholar 

  7. Traggiai C, Stanhope R, Nussey S, Leiper AD. Diabetes mellitus after bone marrow transplantation during childhood. Med Pediatr Oncol. 2003;40:128–9.

    Article  PubMed  CAS  Google Scholar 

  8. Shalitin S, Phillip M, Stein J, Goshen Y, Carmi D, Yaniv I. Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence. Bone Marrow Transpl. 2006;37:1109–17.

    Article  CAS  Google Scholar 

  9. Tahrani AA, Cramp C, Moulik P. The development of non-insulin-dependent diabetes after total body irradiation and bone marrow transplantation in adolescence: a case report and literature review. Pediatr Diabetes. 2006;7:173–5.

    Article  PubMed  Google Scholar 

  10. Majhail NS, Challa TR, Mulrooney DA, Baker KS, Burns LJ. Hypertension and diabetes mellitus in adult and pediatric survivors of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2009;15:1100–7.

    Article  CAS  Google Scholar 

  11. Armenian SH, Sun CL, Vase T, Ness KK, Blum E, Francisco L, et al. Cardiovascular risk factors in hematopoietic cell transplantation survivors: role in development of subsequent cardiovascular disease. Blood. 2012;120:4505–12.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i–xii, 1–253.

  13. Kashiwagi A, Kasuga M, Araki E, Oka Y, Hanafusa T, Ito H, et al. International clinical harmonization of glycated hemoglobin in Japan: from Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J Diabetes Investig. 2012;3:8–10.

    Article  Google Scholar 

  14. American Diabetes Association. Standards of medical care in diabetes-2010. Diabetes Care. 2010;33:S11–61.

    Article  PubMed Central  CAS  Google Scholar 

  15. Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS, et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab. 2004;89:1096–101.

    Article  PubMed  CAS  Google Scholar 

  16. Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med. 1994;11:286–92.

    Article  PubMed  CAS  Google Scholar 

  17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  PubMed  CAS  Google Scholar 

  18. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22:1462–70.

    Article  PubMed  CAS  Google Scholar 

  19. DeFronzo RA, Matsuda M. Reduced time points to calculate the composite index. Diabetes Care. 2010;33:e93.

    Article  PubMed  Google Scholar 

  20. Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care. 2003;12:3320–5.

    Article  Google Scholar 

  21. Neville KA, Cohn RJ, Steinbeck KS, Johnston K, Walker JL. Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: prevalence and risk factors. J Clin Endocrinol Metab. 2006;91:4401–7.

    Article  PubMed  CAS  Google Scholar 

  22. Sheean PM, Freels SA, Helton WS, Braunschweig CA. Adverse clinical consequences of hyperglycemia from total parenteral nutrition exposure during hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2006;12:656–64.

    Article  Google Scholar 

  23. Sheean PM, Braunschweig C, Rich E. The incidence of hyperglycemia in hematopoietic stem cell transplant recipients receiving total parenteral nutrition: a pilot study. J Am Diet Assoc. 2004;104:1352–60.

    Article  PubMed  Google Scholar 

  24. Hammer MJ, Casper C, Gooley TA. The contribution of malglycemia to mortality among allogeneic hematopoietic cell transplant recipients. Biol Blood Marrow Transpl. 2009;15:344–51.

    Article  Google Scholar 

  25. Fuji S, Kim SW, Mori S, Kamiya S, Yoshimura K, Yokoyama H, et al. Intensive glucose control after allogeneic hematopoietic stem cell transplantation: a retrospective matched-cohort study. Bone Marrow Transpl. 2009;44:105–11.

    Article  CAS  Google Scholar 

  26. Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, Marcovecchio ML, et al. Insulin resistance in children consensus conference group insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab. 2010;95:5189–98.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Goran MI, Gower BA. Longitudinal study on puberal insulin resistance. Diabetes. 2001;50:2444–50.

    Article  PubMed  CAS  Google Scholar 

  28. Yu YH, Ginsberg HN. Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ Res. 2005;96:1042–52.

    Article  PubMed  CAS  Google Scholar 

  29. Kadowaki T, Hara K, Yamauchi T, Terauchi Y, Tobe K, Nagai R. Molecular mechanism of insulin resistance and obesity. Exp Biol Med. 2003;228:1111–7.

    CAS  Google Scholar 

  30. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763–70.

    Article  PubMed  CAS  Google Scholar 

  31. Bjørbaek C, Kahn BB. Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res. 2004;59:305–31.

    Article  PubMed  Google Scholar 

  32. Annaloro C, Usardi P, Airaghi L, Giunta V, Forti S, Orsatti A, et al. Prevalence of metabolic syndrome in long-term survivors of hematopoietic stem cell transplantation. Bone Marrow Transpl. 2008;41:797–804.

    Article  CAS  Google Scholar 

Download references

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan

    Kanae Hirabayashi, Yozo Nakazawa, Hiroki Matsuura, Yosuke Hara, Takashi Kurata, Koichi Hirabayashi, Shoji Saito, Kentaro Yoshikawa, Miyuki Tanaka, Ryu Yanagisawa, Kazuo Sakashita & Kenichi Koike

Authors
  1. Kanae Hirabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yozo Nakazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroki Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yosuke Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Kurata
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Koichi Hirabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shoji Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kentaro Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Miyuki Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ryu Yanagisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kazuo Sakashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kenichi Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yozo Nakazawa.

About this article

Cite this article

Hirabayashi, K., Nakazawa, Y., Matsuura, H. et al. Risk factors for diabetes mellitus and impaired glucose tolerance following allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies. Int J Hematol 99, 477–486 (2014). https://doi.org/10.1007/s12185-014-1536-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-014-1536-8

Keywords

Search

Navigation