title: Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Paediatric Endocrinology & Diabetes, Bristol Royal Hospital for Children, Bristol, UK.|St. Georges Hospital, St. Georges Health Care NHS Foundation Trust, London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Paediatric Radiology, Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Manigandan S
authors.initials: MS
authors.lastname: Thyagiarajan
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Hunt
authors.affiliation: Department of Paediatric Endocrinology & Diabetes, Bristol Royal Hospital for Children, Bristol, UK.|Bristol Biomedical Research Unit in Nutrition, University of Bristol, Bristol, UK.
authors.forename: Julian P H
authors.initials: JP
authors.lastname: Shield
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Michael C G
authors.initials: MC
authors.lastname: Stevens
authors.affiliation: Department of Paediatric Endocrinology & Diabetes, Bristol Royal Hospital for Children, Bristol, UK.|School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Crowne
mesh_terms: D050154:Adiposity; D000293:Adolescent; D000328:Adult; D064591:Allografts; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D012307:Risk Factors; D055948:Sarcopenia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017741:Survivors; D014916:Whole-Body Irradiation
keywords: haematopoietic stem cell transplantation; impaired glucose tolerance; insulin sensitivity; lipodystrophy; sarcopenia; total body irradiation