Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation

Rajendran, Rajesh; Abu, E O; Fadl, A.; Byrne, Christopher D.

doi:10.1111/dme.12234

Cited by 30 publications

(32 citation statements)

References 16 publications

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“…Survivors are also at risk for thyroid dysfunction and hypogonadism related to radiation-related target organ damage [27-29]. It is well-established that survivors treated with TBI during childhood are also at increased risk for diabetes [4, 9, 14, 16, 17, 30-32], with risk estimated to be 12.6-fold greater than siblings after adjusting for BMI (95% CI, 6.2–25.3, p < 0.001) [9]. Hyperinsulinemia and insu lin resistance, rather than pancreatic insufficiency, are thought to be the primary pathophysiologic mechanisms underlying diabetes development after TBI [15, 31, 33, 34], although it is likely that other TBI-associated endocrinopathies also contribute to risk [35].…”

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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Section: Diabetesmentioning

confidence: 99%

Diabetes and Metabolic Syndrome in Survivors of Childhood Cancer

2019

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“…The higher prevalence of hypertriglyceridaemia in the HSCT/TBI subjects compared with the obese controls would suggest an aetiology other than simple clinical obesity from excess calorific intake and reduced physical activity. The pathophysiology of dyslipidaemia in HSCT survivors treated with TBI is unclear, although increased hepatic synthesis and/ or reduced clearance of very-low-density lipoprotein due to abnormal lipoprotein lipase activity and increased lipolysis at the adipose tissue have been suggested [25]. Abnormal fat metabolism associated with adipocyte depletion and dysfunction resulting in altered body fat distribution has also been proposed [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology of dyslipidaemia in HSCT survivors treated with TBI is unclear, although increased hepatic synthesis and/ or reduced clearance of very-low-density lipoprotein due to abnormal lipoprotein lipase activity and increased lipolysis at the adipose tissue have been suggested [25]. Abnormal fat metabolism associated with adipocyte depletion and dysfunction resulting in altered body fat distribution has also been proposed [25,26]. It has also been proposed that TBI depletes pre-adipocyte numbers and damages cell architecture, hence limiting its ability to expand.…”

Section: Discussionmentioning

confidence: 99%

Identifying Cardiovascular Risk in Survivors of Childhood Leukaemia Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

et al. 2017

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Background: Survivors of childhood with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have an increased cardiometabolic risk without overt obesity. Aim: To describe cardiometabolic risk in HSCT/TBI survivors and identify anthropometric measurements of adiposity representative of cardiometabolic risks in HSCT/TBI survivors. Method: Childhood leukaemia survivors treated with HSCT/TBI (n = 21, 11 males) were compared with chemotherapy-only (n = 31) and obese non-leukaemic controls (n = 30). All subjects (16–26 years) had blood pressure and auxological measurements (body mass index, waist and hip circumferences) and blood tests (triglycerides, high-density lipoprotein [HDL], and oral glucose tolerance tests). Central adiposity was defined as either increased waist circumference (WC), waist-to-height ratio (WHtR) (>0.5), or waist-to-hip ratio (WHR) (males >0.9, females >0.85). Results: HSCT/TBI survivors showed higher prevalence of hypertriglyceridaemia than both comparison groups and higher prevalence of reduced HDL compared to the chemotherapy-only group. The WHR reported a higher prevalence of increased adiposity in HSCT/TBI survivors compared with WC and WHtR, but such differences were not observed in the other groups. In the HSCT survivors, WHR had the highest number of significant associations with metabolic risk factors, and metabolic risks worsen with time elapsed since primary treatment. Conclusions: HSCT/TBI survivors have high cardiometabolic risk that is not sufficiently reflected by WC alone. WHR is a useful surrogate marker for increased cardiometabolic risk in HSCT/TBI survivors.

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“…HTG has become the most common cause of pancreatitis, aside from biliary and alcoholic pancreatitis 1,3,4 . HLAP has a high mortality rate, a high recurrence rate and has many complications 5,6 . However, the pathogenesis of pancreatitis caused by hypertriglyceridaemia is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Lipoprotein lipase gene-deficient mice with hypertriglyceridaemia associated with acute pancreatitis

et al. 2016

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PURPOSE:To investigate the severity of pancreatitis in lipoprotein lipase (LPL)-deficient hypertriglyceridaemic (HTG) heterozygous mice and to establish an experimental animal model for HTG pancreatitis study. METHODS:LPL-deficient HTG heterozygous mice were rescued by somatic gene transfer and mated with wild-type mice. The plasma amylase, triglyceride, and pathologic changes in the pancreas of the LPL-deficient HTG heterozygous mice were compared with those of wild-type mice to assess the severity of pancreatitis. In addition, acute pancreatitis (AP) was induced by caerulein (50 µg/kg) for further assessment. RESULTS:The levels of plasma amylase and triglyceride were significantly higher in the LPL-deficient HTG heterozygous mice.According to the pancreatic histopathologic scores, the LPL-deficient HTG heterozygous mice showed more severe pathologic damage than the wild-type mice. CONCLUSIONS:Lipoprotein lipase deficient heterozygous mice developed severe caerulein-induced pancreatitis. In addition, their high triglyceride levels were stable. Therefore, LPL-deficient HTG heterozygous mice are a useful experimental model for studying HTG pancreatitis.

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Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation

Cited by 30 publications

References 16 publications

Diabetes and Metabolic Syndrome in Survivors of Childhood Cancer

Diabetes and Metabolic Syndrome in Survivors of Childhood Cancer

Identifying Cardiovascular Risk in Survivors of Childhood Leukaemia Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

Lipoprotein lipase gene-deficient mice with hypertriglyceridaemia associated with acute pancreatitis

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