title: Reduced beta-cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation.
abstract: BACKGROUND
  Impaired glucose tolerance (IGT) and diabetes mellitus (DM) occur more frequently after bone marrow transplantation and total body irradiation (BMT/TBI), but the mechanism is unclear. This study investigates insulin sensitivity, β-cell reserve and pancreatic volume in adult survivors of childhood acute lymphoblastic leukaemia (ALL).
  
  
  METHODS
  Survivors (aged 16-26 years) of ALL treated with BMT/TBI (10-14·4 Gy) Group 1 (n = 20, 10 m) were compared with a chemotherapy-only Group 2 (n = 28, 11 m). Participants underwent assessments of insulin sensitivity by whole body composite-insulin-sensitivity-index (ISIcomp ) from oral glucose tolerance tests (OGTTs); first (AIRarg , AIRg , AUCin10 ) and second (AUC in second phase ) phase insulin responses from arginine-intravenous glucose tolerance tests; and pancreatic volume by abdominal magnetic resonance imaging (MRI). Data were analysed by odds ratio, Chi-square or Fisher's exact tests, Student's t-tests, analysis of covariance (ancova) and Pearson's or partial correlations (5% significance).
  
  
  RESULTS
  Abnormal OGTTs were documented in Group 1 (DM = 2, IGT = 7). Insulin secretion adjusted for insulin sensitivity was lower in Group 1 than Group 2 as a whole [LogAIRarg (P = 0·008), logAIRg (P = 0·013) and logAUCin10 (P = 0·014)] and after exclusion of those with abnormal glucose tolerance [logAIRarg (P = 0·011), logAIRg (P = 0·007) and logAUCin10 (P = 0·006)]. Group 1 had lower pancreatic volume than Group 2 [52·0 (14·2) vs 72·8 (23·5), P = 0·001] cm(3) , and results were consistent after adjustment for size by body surface area (P = 0·019). Pancreatic volume correlated with logAIRarg adjusted log ISIcomp (partial correlation = 0·34, P = 0·025).
  
  
  CONCLUSIONS
  Adult survivors of childhood BMT/TBI for ALL demonstrated reduced β-cell reserve and smaller pancreatic volume, both likely additional aetiological factors, with reduced insulin sensitivity, in their increased risk of diabetes.
authors.affiliation: Departments of Paediatric Endocrinology & Diabetes, Paediatric Oncology and Paediatric Radiology, Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Wei
authors.forename: Manigandan
authors.initials: M
authors.lastname: Thyagiarajan
authors.forename: Linda
authors.initials: L
authors.lastname: Hunt
authors.forename: Rachel
authors.initials: R
authors.lastname: Cox
authors.forename: Karin
authors.initials: K
authors.lastname: Bradley
authors.forename: Ruth
authors.initials: R
authors.lastname: Elson
authors.forename: Julian
authors.initials: J
authors.lastname: Hamilton-Shield
authors.forename: Michael
authors.initials: M
authors.lastname: Stevens
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Crowne
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D017741:Survivors; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult