TY - JOUR
T1 - Reduced beta-cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation
AU - Wei, Christina
AU - Thyagiarajan, Manigandan
AU - Hunt, Linda
AU - Cox, Rachel
AU - Bradley, Karin
AU - Elson, Ruth
AU - Hamilton-Shield, Julian
AU - Stevens, Michael
AU - Crowne, Elizabeth
N1 - © 2014 John Wiley & Sons Ltd.
PY - 2015/1
Y1 - 2015/1
N2 - 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 (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.
AB - 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 (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.
KW - Adolescent
KW - Adult
KW - Bone Marrow Transplantation
KW - Female
KW - Glucose Tolerance Test
KW - Humans
KW - Insulin Resistance
KW - Insulin-Secreting Cells
KW - Male
KW - Pancreas
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - Survivors
KW - Whole-Body Irradiation
KW - Young Adult
U2 - 10.1111/cen.12575
DO - 10.1111/cen.12575
M3 - Article (Academic Journal)
C2 - 25132503
SN - 0300-0664
VL - 82
SP - 59
EP - 67
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 1
ER -
