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      Metabolic syndrome detection with biomarkers in childhood cancer survivors


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          Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (MetS). Risk stratification is difficult after abdominal radiation because waist circumference underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonography.


          The NCEP-ATPIII MetS-components, 14 additional serum biomarkers and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma ( n = 67) and neuroblastoma ( n = 36) survivors and controls ( n = 61). Multivariable regression models were used to study treatment effects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations.


          After 27.5 years of follow-up, MetS occurred more often in survivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with several biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was associated with the unfavourable biomarker profile (β = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value.


          Long-term childhood nephro- and neuroblastoma survivors frequently develop MetS. Additional assessment of biomarkers identified in PCA – adiponectin, LDL, apoB, and uric acid – may be used especially in abdominally irradiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasonography was not of added value.

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          Most cited references23

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          Metabolic syndrome: a clinical and molecular perspective.

          The metabolic syndrome is a cluster of interrelated common clinical disorders, including obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol levels). According to recently defined criteria, the metabolic syndrome is prevalent and is associated with a greater risk of atherosclerotic cardiovascular disease than any of its individual components. Primary defects in energy balance that produce obesity (and visceral adiposity in particular) are sufficient to drive all aspects of the syndrome. Increased free fatty acids and lipid accumulation in certain organs are mediators of insulin resistance. Obesity also leads to a proinflammatory and prothrombotic state that potentiates atherosclerosis. Pathways leading directly from adiposity to the genesis of dyslipidemia and hypertension have been elucidated. Recent knowledge implies a role for fat-derived "adipokines," including TNF alpha and adiponectin, as pathogenic contributors or protective factors. Current therapies include diet and exercise as well as agents indicated for the treatment of individual components of the syndrome. Future therapies may accrue from the aggressive pursuit of newer molecular drug targets that have the potential to prevent or treat multiple aspects of the metabolic syndrome.
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            Diabetes mellitus in long-term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the childhood cancer survivor study.

            Childhood cancer survivors are at increased risk of morbidity and mortality. To further characterize this risk, this study aimed to compare the prevalence of diabetes mellitus (DM) in childhood cancer survivors and their siblings. Participants included 8599 survivors in the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained North American cohort of long-term survivors who were diagnosed between 1970 and 1986 as well as 2936 randomly selected siblings of the survivors. The main outcome was self-reported DM. The mean ages of the survivors and the siblings were 31.5 years (age range, 17.0-54.1 years) and 33.4 years (age range, 9.6-58.4 years), respectively. Diabetes mellitus was reported in 2.5% of the survivors and 1.7% of the siblings. After adjustment for body mass index, age, sex, race/ethnicity, household income, and insurance, the survivors were 1.8 times more likely than the siblings to report DM (95% confidence interval [CI], 1.3-2.5; P < .001), with survivors who received total body irradiation (odds ratio [OR], 12.6; 95% CI, 6.2-25.3; P < .001), abdominal irradiation (OR, 3.4; 95% CI, 2.3-5.0; P < .001), and cranial irradiation (OR, 1.6; 95% CI 1.0-2.3; P = .03) at increased risk. In adjusted models, an increased risk of DM was associated with total body irradiation (OR, 7.2; 95% CI, 3.4-15.0; P < .001), abdominal irradiation (OR, 2.7; 95% CI, 1.9-3.8; P < .001), use of alkylating agents (OR, 1.7; 95% CI, 1.2-2.3; P < .01), and younger age at diagnosis (0-4 years; OR, 2.4; 95% CI, 1.3-4.6; P < .01). Childhood cancer survivors treated with total body or abdominal irradiation have an increased risk of diabetes that appears unrelated to body mass index or physical inactivity.
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              Cohort profile: the EPIC-NL study.


                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                July 2020
                18 June 2020
                : 9
                : 7
                : 676-686
                [1 ]Princess Máxima Centre for Paediatric Oncology , Utrecht, The Netherlands
                [2 ]Department of Paediatric Oncology/Haematology , Erasmus MC–Sophia Children’s Hospital, Rotterdam, The Netherlands
                [3 ]Department of Public Health , Erasmus MC, Rotterdam, The Netherlands
                [4 ]Department of Haematology , Erasmus MC, Rotterdam, The Netherlands
                [5 ]Department of Clinical Chemistry , Erasmus MC, Rotterdam, The Netherlands
                [6 ]Section Endocrinology , Department of Medicine, Erasmus MC, Rotterdam, The Netherlands
                [7 ]Section Geriatric Medicine , Department of Medicine, Erasmus MC, Rotterdam, The Netherlands
                Author notes
                Correspondence should be addressed to V G Pluimakers: v.g.pluimakers@ 123456prinsesmaximacentrum.nl
                Author information
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                : 04 June 2020
                : 18 June 2020

                childhood cancer survivor,metabolic syndrome,nephroblastoma,neuroblastoma,principal component analysis,biomarker


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