Reduced beta‐cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation

Abstract

SummaryBackground 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, b-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 (10-14Á4 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 (OGTTs); 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 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 arg (P = 0Á008), logAIR g (P = 0Á013) and logAUC in10 (P = 0Á014)] and after exclusion of those with abnormal glucose tolerance [logAIR arg (P = 0Á011), logAIR g (P = 0Á007) and logAUC in10 (P = 0Á006)]. Group 1 had lower pancreatic volume than Group 2 [52Á0 (14Á2) vs 72Á8 (23Á5), P = 0Á001] cm 3 , and results were

Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes

“…Adiponectin, a marker of adipocyte function which correlates with insulin sensitivity, was reduced in HSCT/TBI survivors, consistent with previous findings . The observation of a negative correlation between adiponectin and length of time post treatment in HSCT/TBI survivors suggests that cardiometabolic outcomes may worsen with time, in line with the evolving risk of impaired glucose tolerance and reduced insulin sensitivity …”

BMT decreases HFD-induced weight gain associated with decreased preadipocyte number and insulin secretion

“…Our results point to the opposite direction and suggest that BMT may lead to metabolic abnormalities, including reduced insulin secretion and glucose intolerance, which is specifically manifest on HFD. Interestingly, reduced pancreas volume was also observed in survivors of childhood acute lymphoblastic leukaemia who were treated with BMT [19]. In line with our study, several clinical studies suggests that BMT survivors have an increased risk of developing insulin resistance and T2D development [16,10,20].…”

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…Insulin resistance was reported in as many as 52% of longterm HSCT survivors (189). Diabetes and insulin resistance do not seem to be related to obesity, as measured by BMI, in this population (190,191); their pathophysiology seems to involve abnormal body fat distribution and possibly pancreatic islet cell injury due to TBI (192,193). Survivors of solid tumors requiring treatment with abdominal radiotherapy may also have a higher risk of glucose intolerance and diabetes mellitus (76,194,195,196,197).…”