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. Procedure: Survivors of childhood ALL treated with HSCT/TBI (n=20,10M) 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.