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Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.


ABSTRACT: BACKGROUND:Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for both insulin-dependent and non-insulin-dependent diabetes. We sought to clarify the pathophysiology of diabetes after abdRT by performing dynamic studies of insulin and glucose and testing for type 1 diabetes-associated autoantibodies. PROCEDURE:Cross-sectional analysis of 2-year childhood cancer survivors treated with abdRT at age ?21 years who underwent oral glucose tolerance testing and assessment of diabetes-related autoantibodies from December 2014 to September 2016. Prevalence of insulin/glucose derangements, indices of insulin sensitivity/secretion (homeostatic model assessment of insulin resistance [HOMA-IR], whole-body insulin sensitivity, insulinogenic index), autoantibody positivity, and treatment/demographic factors associated with adverse metabolic outcomes were assessed. RESULTS:Among 40 participants previously exposed to abdRT (57.5% male; median age at cancer diagnosis, 3.3 years [range, 0.5-20.1]; median age at study 14.3 years [range, 8.3-49.8]; none with obesity), 9 (22.5%) had glucose derangements (n = 4 with impaired fasting glucose [?100 mg/dL]; n = 4 with impaired glucose tolerance [2-hour glucose 140-199 mg/dL]; n = 1 with previously unrecognized diabetes [2-hour glucose ?200 mg/dL]). Three of the four individuals with impaired fasting glucose also had insulin resistance, as measured by HOMA-IR; an additional four subjects with normal glucose tolerance were insulin resistant. The subject with diabetes had normal HOMA-IR. No participant had absolute insulinopenia or >1 positive diabetes-related autoantibody. CONCLUSIONS:This study suggests that radiation-induced damage to the insulin-producing ?-cells is an unlikely explanation for the early derangements in glucose metabolism observed after abdRT. Research into alternative pathways leading to diabetes after abdRT is needed.

SUBMITTER: Friedman DN 

PROVIDER: S-EPMC6150783 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study.

Friedman Danielle Novetsky DN   Hilden Patrick P   Moskowitz Chaya S CS   Wolden Suzanne L SL   Tonorezos Emily S ES   Antal Zoltan Z   Carlow Dean D   Modak Shakeel S   Cheung Nai-Kong NK   Oeffinger Kevin C KC   Sklar Charles A CA  

Pediatric blood & cancer 20180715 11


<h4>Background</h4>Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for both insulin-dependent and non-insulin-dependent diabetes. We sought to clarify the pathophysiology of diabetes after abdRT by performing dynamic studies of insulin and glucose and testing for type 1 diabetes-associated autoantibodies.<h4>Procedure</h4>Cross-sectional analysis of 2-year childhood cancer survivors treated with abdRT at age ≤21 years who underwent oral glucose tolerance t  ...[more]

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