Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Pediatric Transplants

Glucose metabolism and body composition in young adults treated with TBI during childhood

Bone Marrow Transplantation volume 46, pages 1303–1308 (2011)Cite this article

Subjects

Abstract

After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=−0.52, P=0.032). The patients had a lower peak value of GH (GHmax 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GHmax. The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lorini R, Cortona L, Scaramuzza A, De Stefano P, Locatelli F, Bonetti F et al. Hyperinsulinemia in children and adolescents after bone marrow transplantation. Bone Marrow Transplant 1995; 15: 873–877.

    CAS  PubMed  Google Scholar 

  2. 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: 993–997.

    Article  CAS  PubMed  Google Scholar 

  3. 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: 4401–4407.

    Article  CAS  PubMed  Google Scholar 

  4. 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 Transplant 2006; 37: 1109–1117.

    Article  CAS  PubMed  Google Scholar 

  5. Taskinen M, Lipsanen-Nyman M, Tiitinen A, Hovi L, Saarinen-Pihkala UM . Insufficient growth hormone secretion is associated with metabolic syndrome after allogeneic stem cell transplantation in childhood. J Pediatr Hematol Oncol 2007; 29: 529–534.

    Article  CAS  PubMed  Google Scholar 

  6. Baker KS, Ness KK, Steinberger J, Carter A, Francisco L, Burns LJ et al. Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood 2007; 109: 1765–1772.

    Article  CAS  PubMed  Google Scholar 

  7. Meacham LR, Sklar CA, Li S, Liu Q, Gimpel N, Yasui Y et al. Diabetes mellitus in long-term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the childhood cancer survivor study. Arch Intern Med 2009; 169: 1381–1388.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chemaitilly W, Boulad F, Oeffinger KC, Sklar CA . Disorders of glucose homeostasis in young adults treated with total body irradiation during childhood: a pilot study. Bone Marrow Transplant 2009; 44: 339–343.

    Article  CAS  PubMed  Google Scholar 

  9. Eckel RH, Grundy SM, Zimmet PZ . The metabolic syndrome. Lancet 2005; 365: 1415–1428.

    Article  CAS  PubMed  Google Scholar 

  10. Meacham LR, Gurney JG, Mertens AC, Ness KK, Sklar CA, Robison LL et al. Body mass index in long-term adult survivors of childhood cancer: a report of the Childhood Cancer Survivor Study. Cancer 2005; 103: 1730–1739.

    Article  PubMed  Google Scholar 

  11. Correia ML, Rahmouni K . Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes Obes Metab 2006; 8: 603–610.

    Article  CAS  PubMed  Google Scholar 

  12. Lara-Castro C, Fu Y, Chung BH, Garvey WT . Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease. Curr Opin Lipidol 2007; 18: 263–270.

    Article  CAS  PubMed  Google Scholar 

  13. Nysom K, Holm K, Michaelsen KF, Hertz H, Jacobsen N, Muller J et al. Degree of fatness after allogeneic BMT for childhood leukaemia or lymphoma. Bone Marrow Transplant 2001; 27: 817–820.

    Article  CAS  PubMed  Google Scholar 

  14. Gustafsson G, Kreuger A, Clausen N, Garwicz S, Kristinsson J, Lie SO et al. Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Acta Paediatr 1998; 87: 1151–1161.

    Article  CAS  PubMed  Google Scholar 

  15. Lonnerholm G, Simonsson B, Arvidson J, Bengtsson M, Carlson K, Hagberg H et al. Autologous bone marrow transplantation in children with acute lymphoblastic leukemia. Acta Paediatr 1992; 81: 1017–1022.

    Article  CAS  PubMed  Google Scholar 

  16. Ruiz JR, Rizzo NS, Ortega FB, Loit HM, Veidebaum T, Sjostrom M . Markers of insulin resistance are associated with fatness and fitness in school-aged children: the European Youth Heart Study. Diabetologia 2007; 50: 1401–1408.

    Article  CAS  PubMed  Google Scholar 

  17. Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN . MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 2003; 5: 1003–1015.

    Article  CAS  PubMed  Google Scholar 

  18. Haffner SM, Gonzales C, Miettinen H, Kennedy E, Stern MP . A prospective analysis of the HOMA model: the Mexico City diabetes study. Diabetes Care 1996; 19: 1138–1141.

    Article  CAS  PubMed  Google Scholar 

  19. Oeffinger KC, Adams-Huet B, Victor RG, Church TS, Snell PG, Dunn AL et al. Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 2009; 27: 3698–3704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640–1645.

    Article  CAS  PubMed  Google Scholar 

  21. Jarfelt M, Bjarnason R, Lannering B . Young adult survivors of childhood acute lymphoblastic leukemia: spontaneous GH secretion in relation to CNS radiation. Pediatr Blood Cancer 2004; 42: 582–588.

    Article  CAS  PubMed  Google Scholar 

  22. Bergman RN . Minimal model: perspective from 2005. Horm Res 2005; 64 (Suppl 3): 8–15.

    CAS  PubMed  Google Scholar 

  23. Deeg HJ . Cytokines in graft-versus-host disease and the graft-versus-leukemia reaction. Int J Hematol 2001; 74: 26–32.

    Article  CAS  PubMed  Google Scholar 

  24. Festa A, D'Agostino Jr R, Howard G, Mykkanen L, Tracy RP, Haffner SM . Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000; 102: 42–47.

    Article  CAS  PubMed  Google Scholar 

  25. 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 

  26. Phillips LK, Prins JB . The link between abdominal obesity and the metabolic syndrome. Curr Hypertens Rep 2008; 10: 156–164.

    Article  CAS  PubMed  Google Scholar 

  27. Brauner R, Adan L, Souberbielle JC, Esperou H, Michon J, Devergie A et al. Contribution of growth hormone deficiency to the growth failure that follows bone marrow transplantation. J Pediatr 1997; 130: 785–792.

    Article  CAS  PubMed  Google Scholar 

  28. Frisk P, Arvidson J, Gustafsson J, Lonnerholm G . Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia. Bone Marrow Transplant 2004; 33: 205–210.

    Article  CAS  PubMed  Google Scholar 

  29. Huma Z, Boulad F, Black P, Heller G, Sklar C . Growth in children after bone marrow transplantation for acute leukemia. Blood 1995; 86: 819–824.

    CAS  PubMed  Google Scholar 

  30. Clement-De Boers A, Oostdijk W, Van Weel-Sipman MH, Van den Broeck J, Wit JM, Vossen JM . Final height and hormonal function after bone marrow transplantation in children. J Pediatr 1996; 129: 544–550.

    Article  CAS  PubMed  Google Scholar 

  31. Murray RD, Adams JE, Shalet SM . Adults with partial growth hormone deficiency have an adverse body composition. J Clin Endocrinol Metab 2004; 89: 1586–1591.

    Article  CAS  PubMed  Google Scholar 

  32. Eckel RH, Alberti KG, Grundy SM, Zimmet PZ . The metabolic syndrome. Lancet 2010; 375: 181–183.

    Article  PubMed  Google Scholar 

  33. Antuna-Puente B, Feve B, Fellahi S, Bastard JP . Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 2008; 34: 2–11.

    Article  CAS  PubMed  Google Scholar 

  34. Brennan BM, Rahim A, Blum WF, Adams JA, Eden OB, Shalet SM . Hyperleptinaemia in young adults following cranial irradiation in childhood: growth hormone deficiency or leptin insensitivity? Clin Endocrinol (Oxf) 1999; 50: 163–169.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Swedish Childhood Cancer Foundation (grant no. 05/042), NovoNordisk, the Lions Foundation for Cancer Research at Uppsala University Hospital and the Mary Béve Foundation.

Author information

Authors and Affiliations

  1. Department of Women's and Children's Health, Uppsala University Hospital,

    P Frisk, J Arvidson & J Gustafsson

  2. Uppsala,, Sweden

    P Frisk, J Arvidson & J Gustafsson

  3. Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden

    S M Rössner & S Norgren

Authors
  1. P Frisk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S M Rössner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Norgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Arvidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Gustafsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Frisk.

Ethics declarations

Competing interests

Jan Gustafsson has received consulting fees from Ipsen and lecture fees from NovoNordisk. Jan Gustafsson holds stock options in Pfizer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frisk, P., Rössner, S., Norgren, S. et al. Glucose metabolism and body composition in young adults treated with TBI during childhood. Bone Marrow Transplant 46, 1303–1308 (2011). https://doi.org/10.1038/bmt.2010.307

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.307

Keywords

This article is cited by

Search

Advanced search

Quick links