title: Survivors of childhood leukaemia treated with haematopoietic stem cell transplantation and total body irradiation should undergo screening for diabetes by oral glucose tolerance tests.
abstract: Childhood cancer survivors treated with haematopoietic stem cell transplantation (HSCT) and total body irradiation are at an increased risk of developing diabetes early in life due to insulin resistance and β-cell dysfunction, but the optimal screening method is unknown. The National Institute for Health and Care Excellence guidelines for community diabetes screening recommend using fasting glucose ≥ 7 mmol/l and/or HbA1c ≥ 48 mmol/mol (6.5%) for diagnosis and, fasting glucose 5.5-6.9 mmol/l or HbA1c 42-47 mmol/mol (6-6.5%) to indicate high risk. This study aimed to evaluate the sensitivities of fasting glucose and HbA1c in the diagnosis of diabetes and impaired glucose tolerance in childhood HSCT survivors.
  
  
  
  The patients were 35 (male = 19) HSCT survivors from a single UK centre under follow-up from 2006 to 2013. Patients had a median age (range) of 19.2 (13.1-26.2) years and had been treated for acute lymphoblastic (n = 31) or myeloid (n = 4) leukaemia when aged 7.8 (2.4-16.7) years. The outcome measures were oral glucose tolerance test (OGTT), fasting glucose and HbA1c .
  
  
  
  OGTT identified 6 patients with diabetes (120-min glucose ≥ 11.1 mmol/l), 12 with impaired glucose tolerance (120-min glucose 7.8-11.0 mmol/l) and 2 with impaired fasting glucose (≥ 7 mmol/l). Fasting glucose ≥ 7 mmol/l or HbA1c ≥ 48 mmol/mol identified two of the six patients with diabetes diagnosed on OGTT. Fasting glucose ≥ 5.5 mmol/l and HbA1c ≥ 42 mmol/mol identified three and two patients, respectively, with diabetes. Only 1 of 12 patients with impaired glucose tolerance had a fasting glucose ≥ 5.5 mmol/l and none had HbA1c ≥ 42 mmol/mol (≥ 6%).
  
  
  
  The fasting glucose and HbA1c cut-offs used in UK population screening only identified one-third of HSCT survivors with diabetes and do not identify those at risk. Diabetes screening in HSCT survivors requires standard OGTTs.
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: C
authors.initials: C
authors.lastname: Wei
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: R
authors.initials: R
authors.lastname: Unsworth
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: N
authors.initials: N
authors.lastname: Davis
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: R
authors.initials: R
authors.lastname: Cox
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: K
authors.initials: K
authors.lastname: Bradley
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: M
authors.initials: M
authors.lastname: Stevens
authors.affiliation: Bristol Royal Hospital for Children, Bristol, UK. Liz.Crowne@UHBristol.nhs.uk.
authors.forename: E
authors.initials: E
authors.lastname: Crowne
mesh_terms: D000073116:Cancer Survivors; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000534:rehabilitation / Q000628:therapy*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D012307:Risk Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D006442:Glycated Hemoglobin