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Journal of Pediatric Hematology/Oncology:
Oncology: Original Articles

Diabetes Mellitus in Long-Term Survivors of Pediatric Hematopoietic Cell Transplantation

Hoffmeister, Paul A. MPH*; Storer, Barry E. PhD*; Sanders, Jean E. MD*†

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Abstract

To identify risk factors associated with the development of diabetes mellitus and to describe the prevalence of diabetes in pediatric hematopoietic cell transplant (HCT) survivors. The follow-up records of 748 patients who survived for at least 2 years after pediatric HCT were retrospectively reviewed for diagnosis of diabetes. Risk factors for type 2 diabetes were analyzed using multivariate statistics. Among 748 patients with a median of 11 years of follow-up, 38 developed diabetes after HCT. Four patients (three leukemia and one neuroblastoma) developed type 1 diabetes 8 to 14 years after HCT, at between 10 and 19 years of age. Thirty-four patients (32 leukemia and 2 aplastic anemia) developed type 2 diabetes 1 to 24 years after HCT, at between 11 and 41 years of age. Of the 34 patients with type 2 diabetes, 23 were non-Hispanic white, 3 had experienced asparaginase toxicity (hyperglycemia and/or pancreatitis), and 26 had a family history of diabetes. Risk factors associated with type 2 diabetes were diagnosis of acute or chronic leukemia, race/ethnicity other than non-Hispanic white, family history of diabetes, and asparaginase toxicity. The prevalence of type 1 diabetes among all surviving patients was 0.52%, or three times higher than the general U.S. population. The prevalence of type 2 diabetes was 9% among leukemia survivors and 2% among aplastic anemia survivors, both higher than expected. Pediatric HCT survivors are more likely to develop diabetes than the general population.

Survivors of pediatric hematopoietic cell transplant (HCT) are known to be at risk for developing endocrine abnormalities, including hypothyroidism, hypogonadism, and growth hormone deficiency, due to the effects of chemotherapy and radiation. 1 Recent reports suggest that type 2 diabetes may also be a late effect of pediatric HCT. 2–5

Type 1 diabetes is a progressive, immune-mediated process of β-cell destruction by islet cell antibodies (ICA) that results from an environmental insult in genetically predisposed persons and is associated with certain HLA antigens, including HLA-B8, -DR3, and -DR4. 6,7 HCT recipients have developed type 1 diabetes due to the transfer of type 1 diabetes in bone marrow from donor to host. 8,9

Type 2 diabetes is not associated with autoimmune mechanisms and is believed to result from a combination of insulin resistance and insulin deficiency. 6 Major risk factors for type 2 diabetes include older age, obesity, family history of diabetes, physical inactivity, diet, and race/ethnicity of African American, Hispanic, or Native American. 10 Insulin resistance preceding the onset of diabetes provokes a compensatory increase in insulin secretion. 11 Hyperinsulinemia has been observed in pediatric cancer and HCT survivors. 3,12,13

It is uncertain whether drug or radiation treatments received before, during, or after HCT are risk factors for developing diabetes. Few drugs are known to permanently damage pancreatic β-cells, but some drugs, such as asparaginase and glucocorticoids, are known to cause transient hyperglycemia or acute pancreatitis. 14–18 Impaired glucose tolerance has been observed 6 months following autologous HCT in adult patients treated with total body irradiation (TBI) and non-TBI preparative regimens, although the affect of TBI and busulfan on pancreatic β-cells is unknown. 19,20 Some studies suggest that abdominal radiation and growth hormone therapy may be risk factors for diabetes. 21–25 The individual and cumulative effect of these potential insults on β-cell function and the development of diabetes is unknown. The purpose of this study is to identify risk factors associated with the development of type 2 diabetes and to describe the prevalence of type 1 and type 2 diabetes in a large population of pediatric HCT survivors.

© 2004 Lippincott Williams & Wilkins, Inc.

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