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

Christina Wei, Manigandan S Thyagiarajan, Linda P Hunt, Julian P H Shield, Michael C G Stevens, Elizabeth C Crowne

Journal: Pediatric blood & cancer 2015;62(11):1992-9

PMID: 25989749

Abstract

BACKGROUND

Survivors of childhood acute lymphoblastic leukaemia (ALL) treated with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have a high cardiometabolic risk despite lacking overt clinical obesity. This study characterised body composition using different methodologies and explored associations with reduced insulin sensitivities in a group of ALL survivors treated with/without HSCT/TBI.

PROCEDURE

Survivors of childhood ALL treated with HSCT/TBI (n = 20,10 M) were compared with Chemotherapy-only (n = 31), and an obese non-leukaemic controls (n = 30). All subjects (aged 16-26 years) were investigated with: auxology (BMI, waist and hip circumferences), DEXA (total and regional fat, fat-free mass), abdominal MRI (subcutaneous, visceral, intramuscular fat), oral glucose tolerance tests (impaired glucose tolerance or diabetes, insulin sensitivity) and serum adiponectin.

RESULTS

HSCT/TBI Group displayed a higher prevalence of abnormal glucose tolerance (45%); lower insulin sensitivity; lower lean mass with higher prevalence of reduced fat-free mass index (from DEXA); higher visceral and intramuscular, and lower subcutaneous fat on MRI, compared with the Chemotherapy-only and Obese controls. BMI was lowest in HSCT/TBI Group. Waist-to-hip and android-to-gynoid ratios were similar between HSCT/TBI and Obese Groups. Insulin sensitivity adjusted for visceral fat mass was lower in the HSCT/TBI than the Chemotherapy-only and Obese groups. Adiponectin in the HSCT/TBI Group was lower than the Chemotherapy-only group, and correlated negatively with time post HSCT/TBI.

CONCLUSIONS

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.

© 2015 Wiley Periodicals, Inc.

Address: Department of Paediatric Endocrinology & Diabetes, Bristol Royal Hospital for Children, Bristol, UK.; St. Georges Hospital, St. Georges Health Care NHS Foundation Trust, London, UK.; Department of Paediatric Radiology, Birmingham Children's Hospital, Birmingham, UK.; School of Clinical Sciences, University of Bristol, Bristol, UK.; Bristol Biomedical Research Unit in Nutrition, University of Bristol, Bristol, UK.

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