Reduced beta‐cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation. (1st September 2014)

• Record Type: Journal Article
• Authors: Wei, Christina; Thyagiarajan, Manigandan; Hunt, Linda; Cox, Rachel; Bradley, Karin; Elson, Ruth; Hamilton‐Shield, Julian; Stevens, Michael; Crowne, Elizabeth
• Is Part Of: Clinical endocrinology. Volume 82:Number 1(2015:Jan.)
• Page Start: 59
• Page End: 67
• Publication Date: 2014-09-01
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12575
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12575-abs-0001"> <title>Summary</title> <sec id="cen12575-sec-0001" sec-type="section"> <title>Background</title> <p>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).</p> </sec> <sec id="cen12575-sec-0002" sec-type="section"> <title>Method</title> <p>Survivors (aged 16–26 years) of ALL treated with BMT/TBI (10–14·4 Gy) Group 1 (<italic>n</italic> = 20, 10 <sc>m</sc>) were compared with a chemotherapy‐only Group 2 (<italic>n</italic> = 28, 11 <sc>m</sc>). Participants underwent assessments of insulin sensitivity by whole body composite‐insulin‐sensitivity‐index (ISI<sub>comp</sub>) from oral glucose tolerance tests (OGTTs); first (AIR<sub>arg</sub>, AIR<sub>g</sub>, AUC<sub>in10</sub>) and second (AUC <sub>in second phase</sub>) 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 <italic>t</italic>‐tests, analysis of covariance (<sc>ancova</sc>) and Pearson's or partial correlations (5% significance).</p> </sec> <sec id="cen12575-sec-0003" sec-type="section"> <title>Results</title> <p>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 [LogAIR<sub>arg</sub> (<italic>P</italic> = 0·008), logAIR<sub>g</sub> (<italic>P</italic> = 0·013) and logAUC<sub>in10</sub> (<italic>P</italic> = 0·014)] and after exclusion of those with abnormal glucose tolerance [logAIR<sub>arg</sub> (<italic>P</italic> = 0·011), logAIR<sub>g</sub> (<italic>P</italic> = 0·007) and logAUC<sub>in10</sub> (<italic>P</italic> = 0·006)]. Group 1 had lower pancreatic volume than Group 2 [52·0 (14·2) <italic>vs</italic> 72·8 (23·5), <italic>P</italic> = 0·001] cm<sup>3</sup>, and results were consistent after adjustment for size by body surface area (<italic>P</italic> = 0·019). Pancreatic volume correlated with logAIR<sub>arg</sub> adjusted log ISI<sub>comp</sub> (partial correlation = 0·34, <italic>P</italic> = 0·025).</p> </sec> <sec id="cen12575-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>