Abdominal Radiotherapy: A Major Determinant of Metabolic Syndrome in Nephroblastoma and Neuroblastoma Survivors

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Abstract

Background

Reports on metabolic syndrome in nephroblastoma and neuroblastoma survivors are scarce. Aim was to evaluate the occurrence of and the contribution of treatment regimens to the metabolic syndrome.

Patients and Methods

In this prospective study 164 subjects participated (67 adult long-term nephroblastoma survivors (28 females), 36 adult long-term neuroblastoma survivors (21 females) and 61 control subjects (28 females)). Controls were recruited cross-sectionally. Waist and hip circumference as well as blood pressure were measured. Body composition and abdominal fat were assessed by dual energy X-ray absorptiometry (DXA-scan). Laboratory measurements included fasting triglyceride, high density lipoprotein-cholesterol (HDL-C), glucose, insulin, low-density lipoprotein-cholesterol (LDL-C) and free fatty acids (FFA) levels.

Results

Median age at follow-up was 30 (range 19–51) years in survivors and 32 (range 18–62) years in controls. Median follow-up time in survivors was 26 (6–49) years. Nephroblastoma (OR = 5.2, P<0.0001) and neuroblastoma (OR 6.5, P<0.001) survivors had more components of the metabolic syndrome than controls. Survivors treated with abdominal irradiation had higher blood pressure, triglycerides, LDL-C, FFA and lower waist circumference. The latter can not be regarded as a reliable factor in these survivors as radiation affects the waist circumference. When total fat percentage was used as a surrogate marker of adiposity the metabolic syndrome was three times more frequent in abdominally irradiated survivors (27.5%) than in non-irradiated survivors (9.1%, P = 0.018).

Conclusions

Nephroblastoma and neuroblastoma survivors are at increased risk for developing components of metabolic syndrome, especially after abdominal irradiation. We emphasize that survivors treated with abdominal irradiation need alternative adiposity measurements for assessment of metabolic syndrome.

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Most cited references 16

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Banting lecture 1988. Role of insulin resistance in human disease.

G M Reaven (1988)

Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one.(ABSTRACT TRUNCATED AT 400 WORDS)

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The perils of portliness: causes and consequences of visceral adiposity.

Mamie C Montague, S O'Rahilly (2000)

Although an individual's total fat mass predicts morbidities such as coronary artery disease and diabetes, the anatomical distribution of adipose tissue is a strong and independent predictor of such adverse health outcomes. Thus, obese individuals with most of their fat stored in visceral adipose depots generally suffer greater adverse metabolic consequences than similarly overweight subjects with fat stored predominantly in subcutaneous sites. A fuller understanding of the biology of central obesity will require information regarding the genetic and environmental determinants of human fat topography and of the molecular mechanisms linking visceral adiposity to degenerative metabolic and vascular disease. Here we attempt to summarize the growing body of data relevant to these key areas and, in particular, to illustrate how recent advances in adipocyte biology are providing the basis for new pathophysiological insights.

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Cardiovascular risk factors in adult survivors of pediatric cancer--a report from the childhood cancer survivor study.

Peter P. C. Mertens, E Chow, Leslie Robison … (2009)

Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular disease compared with the general population. Eight thousand five hundred ninety-nine survivors (52% male) and 2,936 siblings (46% male) from the Childhood Cancer Survivor Study, a retrospectively ascertained, prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970 to 1986, were evaluated for body mass index of > or =30 kg/m(2) based on self-reported heights and weights and self-reported use of medications for hypertension, dyslipidemia, and impaired glucose metabolism. The presence of three or more of the above constituted Cardiovascular Risk Factor Cluster (CVRFC), a surrogate for Metabolic Syndrome. Survivors were more likely than siblings to take medications for hypertension [odds ratio (OR), 1.9; 95% confidence interval (95% CI), 1.6-2.2], dyslipidemia (OR, 1.6; 95% CI, 1.3-2.0) or diabetes (OR, 1.7; 95% CI, 1.2-2.3). Among these young adults (mean age of 32 years for survivors and 33 years for siblings), survivors were not more likely than siblings to be obese or have CVRFC. In a multivariable logistic regression analysis, factors associated with having CVRFC included older age at interview [> or =40 versus <30 years of age (OR, 8.2; 95% CI, 3.5-19.9)], exposure to total body irradiation (OR, 5.5; 95% CI, 1.5-15.8) or radiation to the chest and abdomen (OR, 2.3; 95% CI, 1.2-2.4), and physical inactivity (OR, 1.7; 95% CI, 1.1-2.6). Among adult survivors of pediatric cancer, older attained age, exposure to total body irradiation or abdominal plus chest radiation, and a sedentary life-style are associated with CVRFC.

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Author and article information

Contributors

Cordula M. Stover: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2012

Publication date (Electronic): 14 December 2012

Volume: 7

Issue: 12

Electronic Location Identifier: e52237

Affiliations

[1 ]Department of Pediatric Oncology/Hematology, Erasmus MC - Sophia Children’s Hospital Rotterdam, Rotterdam, The Netherlands

[2 ]Department of Medicine, Section Endocrinology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

[3 ]Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands

[4 ]Department of Radiation Oncology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

University of Leicester, United Kingdom

Author notes

* E-mail: m.vandenheuvel@ 123456erasmusmc.nl

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: SN HR RP MVDH. Performed the experiments: MVW SN. Analyzed the data: MVW. Contributed reagents/materials/analysis tools: CVR. Wrote the paper: MVW SN HR CVR RP MVDH.

Article

Publisher ID: PONE-D-12-18634

DOI: 10.1371/journal.pone.0052237

PMC ID: 3522621

PubMed ID: 23251703

SO-VID: 414fa52f-b37a-4ace-8bd4-7792d472e2e7

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 27 June 2012

Date accepted : 9 November 2012

Page count

Pages: 9

Funding

The authors thank KiKa (Kinderen Kankervrij) (Grant number 2009-030) and KOCR (Kinderoncologisch Centrum Rotterdam) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Abdominal Radiotherapy: A Major Determinant of Metabolic Syndrome in Nephroblastoma and Neuroblastoma Survivors

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Abstract

Background

Patients and Methods

Results

Conclusions

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PLOS Climate

Most cited references 16

Banting lecture 1988. Role of insulin resistance in human disease.

The perils of portliness: causes and consequences of visceral adiposity.

Cardiovascular risk factors in adult survivors of pediatric cancer--a report from the childhood cancer survivor study.

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