Background: Adult survivors of childhood leukaemia treated Bone marrow transplantation with total body irradiation (BMT/TBI) have an increased risk of diabetes mellitus (DM) disproportionate to their level of adiposity or other recognised risk factors. Post prandial hyperglycaemia due to reduced β-cell reserve after irradiation will be missed by fasting glucose (FG) levels. However, the UK National Institute of Clinical Excellence (NICE) screening guidelines recommend the use of fasting glucose (FG) >7 mmol/l and/or HbA1c>48 mmol/mmol for the diagnosis of DM and, FG 5.56.9 mmol/l or HbA1c 4247 mmol/mmol to indicate high risk.
Objective: To evaluate sensitivity of the UK national screening criteria in the diagnosis of DM in survivors of childhood BMT/TBI.
Method: Subjects: 37 (M=19) BMT/TBI survivors from a single UK centre 20062013, mean age (S.D.) 18.9 (3.1) years treated for acute lymphoblastic leukaemia (n=31) and acute myeloid leukaemia (n=6) by BMT/TBI at 7.9 (3.8) years of age. Outcome measures: demographic and treatment details, results of OGTT and HbA1c, prevalence of hypertension (>130/85), hypertriglycerides (>1.7 mol/l) and reduced high density lipoprotein(HDL) (M<1.03, F<1.29 mmol/l).
Results: OGTT results revealed 6 (16.2%) with DM (120 minute glucose>11.1 mmol/l), 13 (37.1%) with impaired glucose tolerance (120 min glucose 7.811.1 mmol/l) and 2 (5%) with impaired FG (>7 mmol/l). NICE screening criteria for DM with FG (>7 mmol/l) or HbA1c (>48 mmol/mmol) identify 2/6 (33%) patients with DM. The lower cut-offs recommended for higher risk patients with FG >5.5 mmol/L and HbA1c >42 mmol/mmol identify 3/6 (50%) and 2/6 (33%) with DM respectively. In addition, only 1/13 (7.7%) with impaired glucose tolerance had a FG of >5.5 mmol/l and none had HbA1c >42 mmol/mmol. BMT/TBI survivors had a high prevalence of hypertension (16%), hypertriglyceridaemia (62%), and reduced HDL (35%).
Conclusions: There is a high prevalence of abnormal glucose tolerance and metabolic abnormalities in BMT/TBI survivors. Standard screening criteria under NICE with FG and HbA1c will miss 67% of those with DM and therefore do not identify those at risk. Screening of DM in BMT/TBI survivors requires standard OGTTs although the optimal frequency needs ongoing evaluation.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology