Abstract
Impairment of glucose metabolism (in particular insulin resistance and type 2 diabetes mellitus) has been reported in patients who have undergone hematopoietic SCT (HSCT) during childhood, especially those treated with TBI. This pilot study was conducted to determine prevalence of and possible underlying mechanisms for impaired glucose homeostasis in young adults treated with HSCT and TBI and who were not previously known to have diabetes mellitus. A total of 10 subjects (6 males, 4 females) were evaluated. Mean ages were 13.0±1.0 years at the time of TBI and 24.0±1.1 years at the time of this study. Five subjects had laboratory evidence of insulin resistance using the homeostasis model assessment and the quantitative insulin sensitivity check index indices. Two of these subjects had impaired fasting glucose and four had decreased plasma insulin-like growth factor 1 levels. All 10 subjects had evidence of abdominal obesity. Insulin resistance is frequently observed in adult survivors of HSCT treated with TBI in childhood. Underlying mechanisms may include radiation-induced growth hormone deficiency and changes in body composition.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ries LAG, Harkins D, Krapcho M, Mariotto A, Miller BA, Feuer EJ et al. (eds). SEER Cancer Statistics Review, 1975–2003. National Cancer Institute: Bethesda, 2006.
Hows JM, Passweg JR, Tichelli A, Locasciulli A, Szydlo R, Bacigalupo A et al. Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors. Bone Marrow Transplant 2006; 38: 799–805.
d'Annunzio G, Bonetti F, Locatelli F, Pistorio A, Lorini R . Insulin resistance in children and adolescents after bone marrow transplantation for malignancies. Haematologica 2006; 91 (12 Suppl): ELT12.
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.
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.
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.
Traggiai C, Stanhope R, Nussey S, Leiper AD . Diabetes mellitus after bone marrow transplantation during childhood. Med Pediatr Oncol 2003; 40: 128–129.
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.
Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D et al. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med 1987; 317: 1618–1624.
Yahalom J, Fuks ZY . Strategies for the use of total body irradiation as systemic therapy in leukemia and lymphoma. In: Armitage JO, Antman KH (eds). High Dose Cancer Therapy. Williams and Wilkins: Baltimore, 1992, p61.
World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i–xii, 6–13.
Expert committee on the diagnosis and classification of diabetes mellitus: report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–1197.
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; 26: 3320–3325.
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: 1096–1101.
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402–2410.
Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23: 57–63.
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.
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.
Lee S, Bacha F, Gungor N, Arslanian S . Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal obesity, insulin resistance, adiponectin and inflammatory biomarkers. J Pediatr 2008; 152: 177–184.
Oeffinger KC, Mertens AC, Sklar CA, Yasui Y, Fears T, Stovall M et al. Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003; 21: 1359–1365.
Sklar CA, Mertens AC, Walter A, Mitchell D, Nesbit ME, O'Leary M et al. Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: role of cranial irradiation. Med Pediatr Oncol 2000; 35: 91–95.
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.
Papadimitrou A, Uruena M, Stanhope R, Leiper AD . Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation. Arch Dis Child 1991; 66: 689–692.
Ogilvy-Stuart AL, Clark DJ, Wallace WHB, Gibson BE, Stevens RF, Shalet S et al. Endocrine deficit after fractionated total body irradiation. Arch Dis Child 1992; 67: 1107–1110.
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.
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.
Gurney JG, Ness KK, Sibley SD, O'Leary M, Dengel DR, Lee JM et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer 2006; 107: 1303–1312.
Menzaghi C, Trischitta V, Doria A . Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 2007; 56: 1198–1209.
Boden G, Shulman GI . Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest 2002; 32 (Suppl 3): 14–23.
Haap M, Fritsche A, Mensing HJ, Häring HU, Stumvoll M . Association of high serum ferritin concentration with glucose intolerance and insulin resistance in healthy people. Ann Intern Med 2003; 139: 869–871.
Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 2006; 55: 2688–2697.
Acknowledgements
This study was supported by a grant from the Society of Memorial Sloan-Kettering.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chemaitilly, W., Boulad, F., Oeffinger, K. et al. Disorders of glucose homeostasis in young adults treated with total body irradiation during childhood: a pilot study. Bone Marrow Transplant 44, 339–343 (2009). https://doi.org/10.1038/bmt.2009.40
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2009.40
Keywords
This article is cited by
-
A systematic approach to the endocrine care of survivors of pediatric hematopoietic stem cell transplantation
Cancer and Metastasis Reviews (2020)
-
Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review
Journal of Cancer Survivorship (2020)
-
Volumetric decrease of pancreas after abdominal irradiation, it is time to consider pancreas as an organ at risk for radiotherapy planning
Radiation Oncology (2018)
-
Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells
Annals of Hematology (2018)
-
Total body irradiation for hematopoietic stem cell transplantation during early childhood is associated with the risk for diabetes mellitus
Endocrine (2018)