ESPE Abstracts (2014) 82 P-D-1-2-29

Standard Population Screening for Diabetes Mellitus has Low Sensitivity in Identifying Diabetes in Adult Survivors of Childhood Bone Marrow Transplantation with Total Body Irradiation

Christina Weia,b, Rebecca Unswortha, Nikki Davisa,c, Ruth Elsona, Karin Bradleya,d, Michael Stevensa,d & Elizabeth Crownea,d

aUniversity Hospitals Bristol NHS Foundation Trust, Bristol, UK; bSt Georges Hospital, St Georges Health Care NHS Trust, London, UK; cUniversity Hospital Southampton NHS Foundation Trust, Southampton, UK; dUniversity of Bristol, Bristol, UK

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 5.5–6.9 mmol/l or HbA1c 42–47 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 2006–2013, 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 7.8–11.1 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.