Reduction in Beta-cell function and Pancreatic Volume in adult survivors of Childhood Acute Lymphoblastic Leukaemia (ALL) treated with Bone Marrow Transplantation (BMT) and Total Body Irradiation (TBI)

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 758-775-Beta Cells, Glucose Control & Complications
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-763
Christina Wei*1, Manigandan Thyagarajan1, Linda P Hunt2, Karin Jane Bradley3, Ruth Elson1, Michael CG Stevens4 and Elizabeth C Crowne1
1Bristol Royal Hospital for Children, Bristol, United Kingdom, 2School of Clinical Sciences, University of Bristol, Bristol, United Kingdom, 3Bristol Royal Infirmary, Bristol, United Kingdom, 4University of Bristol, Bristol, United Kingdom
Background: Adult survivors of childhood ALL treated with BMT and total body irradiation(TBI) have increased risk of impaired glucose tolerance(IGT) and diabetes mellitus(DM). Insulin resistance(IR) has been described in these patients, but effects of TBI on pancreatic growth and beta(b)-cell function have not been previously reported.

Method: Two groups of childhood ALL survivors were studied: Group 1) Treated with(n=21,11M) and Group 2) without(n=31,13M) BMT/TBI. BMT/TBI survivors received 10-14.4Gy TBI at mean age 9.3(1.0-10.8) yr. A control Group 3) was selected of obese subjects (n=30,10M). All were age 16-26yr at time of study and had assessment of: pancreatic volume by abdominal MRI; IR by insulin composite insulin sensitivity index(ISIcomp) from oral glucose tolerance test(OGTT); and b-cell function by acute-insulin-response(AIR) from Arginine intravenous glucose tolerance test(AIRarg). Data were logarithmically transformed if positively skewed and analysed by ANOVA with post-hoc Scheffé’s multiple comparison tests, multiple regression and Pearson's correlations at 5% significance. Results are reported as mean(SD) or geometric means(range) as appropriate.

Results: Abnormal OGTT were reported in Groups 1(DM=2,IGT=7) and 3(IGT=1). ISIcomp was lower in Groups 1[1.7(0.35-44.7) p<0.001] and 3[4.8(0.75-9.6) p=0.001] compared with Group 2[2.2(0.76-7.5)]. b-cell function assessed in the context of IR was significantly lower in Group 1 [60.0(CI:43.8-76.7)] than in Groups 2[105.4(CI:79.8-138.4) p=0.003] and 3[83.8(CI:69.7-100.9) p=0.034]. Absolute pancreatic volume(cm3) (PV) was lower in Group 1[52.0(14.2)] than in Groups 2[72.8(23.5),p=0.003] and 3[72.8(19.7),p=0.006] and correlated with AIR (r=0.3,p=0.01). As PV correlated positively with height (r=0.45,p<0.001) and as Group1 were shorter (p<0.001) than Groups 2 or 3 (height SDS: -1.4(1.5); 0.2(0.9) and 0.5(1.0) respectively), PV was corrected for height(cm3/m2) but remained less in Group 1[19.9(5.5)] than in Group 2[24.9(8.0) p=0.048] or 3[25.6(6.6) p=0.03]. PV did not differ between Groups 2 and 3(p=1.0) and did not correlate with age at ALL diagnosis(p=0.9), time from treatment(p=0.3), age at BMT(p=0.7), time from BMT(p=0.3) or TBI dose(p=0.8).

Conclusions: This study suggests that reduction in pancreatic size, and loss of b-cell compensation contribute, with increased IR, to the mechanism of abnormal glucose homeostasis in survivors of BMT/TBI in childhood.

Nothing to Disclose: CW, MT, LPH, KJB, RE, MCS, ECC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm