Endocrine Abstracts

Background: Adult survivors of childhood acute lymphoblastic leukaemia (ALL) treated with bone marrow transplantation (BMT) and total body irradiation (TBI) have increased risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Insulin resistance (IR) has been described, but effects of TBI on pancreatic growth and β-cell function have not been previously reported.

Method: Two groups of childhood ALL survivors were studied: Group 1, treated with (n=21, 11 M) and Group 2, without (n=31, 13 M) BMT/TBI. BMT/TBI survivors received 10–14.4 Gy TBI at mean age 9.3 (1.0–10.8) years. A control Group 3, was selected of obese subjects (n=30, 10 M). All were age 16–26 years and had assessment of: pancreatic volume by abdominal MRI; IR by insulin composite insulin sensitivity index (ISIcomp) from oral glucose tolerance test (OGTT); β-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 (S.D.) 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)). β-cell function assessed in the context of IR was significantly lower in Group 1 [60.0 (CI: 43.8–76.7)) than 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 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). Pancreatic volume correlated positively with the size (represented by height²) of participants (r=0.45, P<0.001). Regression analysis confirmed that PV adjusted for size remained lower in Group 1 (56 (47.4–65.1)) than Groups 2 (71.0 (63.8–78.2), P=0.014) or 3 ((71.2 (63.2–79.3), P=0.016). Absolute and corrected 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 β-cell compensation contribute, with increased IR, to the mechanism of abnormal glucose homeostasis in survivors of BMT/TBI in childhood.