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Reduced beta‐cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation
Author(s) -
Wei Christina,
Thyagiarajan Manigandan,
Hunt Linda,
Cox Rachel,
Bradley Karin,
Elson Ruth,
HamiltonShield Julian,
Stevens Michael,
Crowne Elizabeth
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12575
Subject(s) - medicine , total body irradiation , insulin , gastroenterology , body mass index , endocrinology , transplantation , insulin resistance , odds ratio , area under the curve , bone marrow , urology , chemotherapy , cyclophosphamide
Summary 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 ). Method 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 ( ISI comp ) from oral glucose tolerance tests ( OGTT s); first ( AIR arg , AIR g , AUC in10 ) 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 OGTT s 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 [Log AIR arg ( P = 0·008), log AIR g ( P = 0·013) and log AUC in10 ( P = 0·014)] and after exclusion of those with abnormal glucose tolerance [log AIR arg ( P = 0·011), log AIR g ( P = 0·007) and log AUC in10 ( 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 log AIR arg adjusted log ISI comp (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.