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

Friedman, Danielle Novetsky; Hilden, Patrick; Moskowitz, Chaya S.; Wolden, Suzanne L.; Tonorezos, Emily S.; Antal, Zoltan; Carlow, Dean; Modak, Shakeel; Cheung, Nai‐Kong V.; Oeffinger, Kevin C.; Sklar, Charles A.

doi:10.1002/pbc.27304

Cited by 14 publications

(11 citation statements)

References 34 publications

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“…Also, HL patients required abdominal and cervical irradiation, yet we retrieved only TBI as a risk of hyperglycaemia development in our ALL cohort. Abdominal, cervical and cranial radiation did not appear to induce hyperglycaemia in our study, although this is contrary to findings in other studies which suggested the effect of abdominal radiation 30–32 . Strengths of our study include the large sample size of ALL patients, inclusion of risk factors for hyperglycaemia, complete patient records and numerous harmonized blood glucose data for ALL and NHL.…”

Section: Discussioncontrasting

confidence: 99%

“…Abdominal, cervical and cranial radiation did not appear to induce hyperglycaemia in our study, although this is contrary to findings in other studies which suggested the effect of abdominal radiation. 30 , 31 , 32 Strengths of our study include the large sample size of ALL patients, inclusion of risk factors for hyperglycaemia, complete patient records and numerous harmonized blood glucose data for ALL and NHL. Furthermore, we studied the incidence of hyperglycaemia from the initiation of cancer treatment and not only during remission (after 2 years).…”

Section: Discussionmentioning

confidence: 99%

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Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies

et al. 2021

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies

et al. 2021

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“…Regarding the pathophysiology of diabetes after abdominal radiation, the epidemiologic data would suggest that damage to the insulin-producing b cells concentrated in the tail of the pancreas is the key etiologic factor in development of diabetes in this population. However, the limited clinical data regarding the role of insulinopenia in the development of diabetes after abdominal radiation are inconsistent (22); moreover, more recent data suggest a role for insulin resistance rather than insulinopenia in the pathogenesis of diabetes (26). Further studies to clarify the mechanisms leading to diabetes after abdominal radiation are warranted.…”

Section: Discussionmentioning

confidence: 99%

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study

Friedman

Moskowitz

Hilden

et al. 2019

JNCI: Journal of the National Cancer Institute

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Background Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear. Methods Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided. Results Survivors exposed to abdRT (median age = 31.6 years, range = 10.2–58.3 years) were 2.92-fold more likely than siblings (95% confidence interval [CI] = 2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI = 1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RRper 10 years = 2.11, 95% CI = 1.70 to 2.62), higher body mass index (RRBMI 30+ = 5.00, 95% CI = 3.19 to 7.83 with referenceBMI 18.5–24.9), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (P < .001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk. Conclusions Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.

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“…Our group recently evaluated pancreatic autoantibody status (glutamic acid decarboxylase [GAD-65], insulin autoantibodies, islet antigen-2) in 40 survivors of childhood cancer exposed to abdominal radiation [58]. While a variety of glucose and insulin derangements were noted in this investigation, none of the participants had more than one positive pancreatic autoantibody, suggesting that autoimmunity is not the underlying etiology of posttherapy diabetes.…”

Section: Diabetesmentioning

confidence: 99%

Diabetes and Metabolic Syndrome in Survivors of Childhood Cancer

2019

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Endocrine complications, including diabetes and metabolic syndrome, are highly prevalent in childhood cancer survivors. These metabolic derangements may contribute to survivors’ risk of excess cardiovascular morbidity and premature mortality. This review summarizes existing knowledge on risk of diabetes and metabolic syndrome among childhood cancer survivors, focusing specifically on known risk factors, potential mechanisms, and screening recommendations. Early diagnosis via standardized risk-based screening can improve long-term outcomes in this population. Additional work is needed to elucidate the mechanisms underlying these metabolic complications and to inform the design of risk-reducing interventions and optimize long-term cardiometabolic health among survivors of childhood cancer.

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

Abstract: This study suggests that radiation-induced damage to the insulin-producing β-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.

Cited by 14 publications

References 34 publications

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study

Diabetes and Metabolic Syndrome in Survivors of Childhood Cancer

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