Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes

Wei, Christina; Thyagiarajan, Manigandan; Hunt, Linda; Shield, Julian P H; Stevens, Michaël C.G.; Crowne, Elizabeth

doi:10.1002/pbc.25601

Cited by 70 publications

(67 citation statements)

References 53 publications

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“…Loss of lean mass in HSCT-TBI survivors may be associated with treatment toxicity linked to TBI, chemotherapy, and additional steroids for the treatment of GVHD. We have demonstrated reduction in lean mass in HSCT-TBI survivors consistent with that previously reported [13], but we have not found a relationship between lean mass and BMAD in our study. This may be due to the limited duration of follow-up after HSCT-TBI and as reduction in lean mass continues with time, this may also have an effect on ongoing BMD reduction and should be further evaluated.…”

Section: Discussionsupporting

confidence: 82%

“…In addition, the ISCD guidelines have not only emphasised the need for size correction in children with short stature, but also the adjustment for soft-tissue measurements in the presence of malnutrition and skeletal muscle deficits [11]. This is particularly relevant to children with chronic diseases, such as in the case of HSCT-TBI survivors, where short stature [12] and reduced lean muscle mass [13] are common as a result of GHD, hypogonadism, hypothyroidism, steroid therapy, and/or poor nutrition.…”

Section: Introductionmentioning

confidence: 99%

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Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

et al. 2018

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Background: Childhood leukaemia survivors treated with haematopoietic stem cell transplantation and total body irradiation (HSCT-TBI) have multiple risk factors for reduced bone mineral density (BMD) and growth failure; hence, BMD assessment must take body size into consideration. This study aimed to evaluate size-corrected BMD in leukaemia survivors treated with and without HSCT-TBI. Methods: Childhood leukaemia survivors treated with HSCT-TBI (n = 35), aged 17.3 (10.5–20.9) years, were compared with those treated with chemotherapy only, (n = 16) aged 18.5 (16.1–20.9) years, and population references. Outcome measures included anthropometric measurements and BMD by dual-energy X-ray absorptiometry. BMD was corrected for size as bone mineral apparent density (BMAD). Statistical analysis was performed by 1- and 2-sample t tests as well as regression analysis (5% significance). Results: HSCT-TBI survivors were lighter and shorter with reduced spinal heights compared with chemotherapy-only subjects and population references. Compared with population references, HSCT-TBI survivors showed lower BMD standard deviation scores (SDS) (p = 0.008), but no difference in BMAD-SDS, and chemotherapy-only survivors showed no differences in neither BMD-SDS nor BMAD-SDS. All HSCT-TBI participants with BMD-SDS <–2 had BMAD-SDS >–2. BMAD-SDS was negatively associated with age (r = –0.38, p = 0.029) in HSCT-TBI survivors. Conclusions: Size-corrected BMD are normal in HSCT-TBI survivors in young adulthood, but may reduce overtime. BMD measurements should be corrected for size in these patients to be clinically meaningful.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

et al. 2018

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“…Specifically, those treated with TBI demonstrate increased total fat mass and decreased lean body mass and muscle mass, despite similarities in BMI to controls [36, 40]. TBI-exposed survivors also demonstrate an unfavorable profile of inflammation and altered adipokines (higher leptin/lower adiponectin) [40, 41].…”

Section: Diabetesmentioning

confidence: 99%

“…Recent work has demonstrated that young adult HCT survivors are at risk for adverse cardiometabolic phenotypes consistent with sarcopenic obesity [36-39], which is typically observed in elderly populations at increased risk for adverse health events. Specifically, those treated with TBI demonstrate increased total fat mass and decreased lean body mass and muscle mass, despite similarities in BMI to controls [36, 40].…”

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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“…However, while cardiometabolic risk in the general population is easily identified by measures of obesity, this is not straightforward in HSCT/TBI survivors since they do not appear overtly obese [8,9]. The metabolic syndrome is a constellation of cardiovascular risk factors including central adiposity, hyperlipidaemia, hypertension, and abnormal glucose tolerance.…”

Section: Introductionmentioning

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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Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes

Abstract: HSCT/TBI survivors have an increased risk of abnormal glucose tolerance and reduced insulin sensitivity with reduced subcutaneous and increased visceral fat distribution, increased total fat mass and reduced lean mass.

Cited by 70 publications

References 53 publications

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

Bone Mineral Density Corrected for Size in Childhood Leukaemia Survivors Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

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

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