| Summary: | Background: Impaired glucose tolerance and diabetes mellitus are increasingly recognised in survivors of bone marrow transplantation and total body irradiation (BMT/TBI). Aim: To investigate mechanisms leading to increased risk of diabetes in childhood survivors of acute lymphoblastic leukaemia (ALL) treated with BMT/TBI. Method: Childhood ALL survivors treated with BMTITBI (1 0-14.4Gy) (Group1, n=20,1 OM) were compared with a chemotherapy only Group 2 (n=28, 11 M), and an obese otherwise healthy Group 3 (n=22,7M). All were aged 16-26 and had assessments of metabolic profile (auxology, blood pressure, lipids, adipocytokines), insulin sensitivity (oral glucose tolerance tests), ~-cell function (arginine intravenous glucose tolerance tests), body composition [Dual energy X-Ray absorptiometry scan (DEXA) and magnetic resonant imaging(MRI)] and pancreatic volume (MRI). Results: Group1 had a higher prevalence of abnormal glucose tolerance and hypertriglyceridaemia than Groups 2 and 3; and reduced high density lipoprotein and abnormal insulin sensitivity compared with Group 2. In Group 1, metabolic abnormalities were not associated with body mass index, but with waist-to-hip ratio. Group 1 showed lower insulin secretion adjusted for insulin sensitivity than Groups 2 and 3. Size adjusted pancreatic volume was smaller in Group 1 than Groups 2 or 3. Group 1 had a higher prevalence of reduced fat-free mass than Groups 2 and 3, and lower mean lean mass index than Group 3. Group 1 showed lower total and truncal fat masses, but no difference in android-to-gynoid ratio than Group 3. Group 1 showed a higher visceral and intramuscular, but lower percentage and overall distribution of subcutaneous fat compared with Groups 2 and 3. Insulin sensitivity was lower for the same degree of central fat mass in Group 1. Adiponectin levels were lower in Group 1 than 2 and correlated negatively with time post BMT/TBI. Conclusions: Reduced ~-cell reserve with smaller pancreatic volume, reduced insulin sensitivity with higher visceral and intramuscular, and reduced subcutaneous fat distribution contribute to the increased risk of abnormal glucose tolerance in BMTITBI survivors.
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