title: Interpretation of HbA1c : association with mean cell volume and haemoglobin concentration.
abstract: OBJECTIVE
  The utility of HbA1c in diabetes diagnosis is reduced in settings associated with altered haemoglobin glycation. We have studied whether HbA1c varies with mean cell volume and mean cell haemoglobin concentration as measures of haemoglobin metabolism.
  
  
  METHODS
  Randomly selected adults from rural Victoria, Australia, were invited for biomedical assessment. After excluding patients with known diabetes and/or serum creatinine ≥ 0.12 mmol/l, 1315 adults were included. Demography, arthropometric measurements, oral glucose tolerance test, analyses of full blood count and HbA1c were undertaken.
  
  
  RESULTS
  After adjusting for age, sex, ethnicity, BMI, town and socio-economic status, there were no significant differences in haemoglobin, mean cell volume or mean cell haemoglobin concentration by glycaemic status (defined by oral glucose tolerance test). HbA1c was significantly and independently associated with fasting glucose, town, mean cell haemoglobin concentration, ethnicity, age and BMI among men < 50 years (R² = 33.8%); fasting glucose, 2-h glucose, mean cell haemoglobin concentration and town among men ≥ 50 years (R² = 47.9%); fasting glucose, mean cell volume, mean cell haemoglobin concentration, town, 2-h glucose and age among women < 50 years (R² = 46.3%); fasting glucose, mean cell haemoglobin concentration, mean cell volume and 2-h glucose among women ≥ 50 years (R² = 51.6%). A generalized linear model showed a gradient from an adjusted mean HbA1c of 36 (95% CI 34-38) mmol/mol with a mean cell haemoglobin concentration of ≤ 320 g/l to 30 (95% CI 29-31) mmol/mol with a mean cell haemoglobin concentration of > 370 g/l. The gradient across mean cell volume was negative, but only by 1 mmol/mol (0.1%) HbA1c .
  
  
  CONCLUSIONS
  A mean HbA1c difference of 5 mmol/mol (0.5%) across the mean cell haemoglobin concentration reference range suggests that an accompanying full blood count examination may be required for its use in the diagnosis of diabetes. Further studies are required to confirm this.
authors.affiliation: Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Rural Health, University of Melbourne Shepparton, Vic., Australia.
authors.forename: D
authors.initials: D
authors.lastname: Simmons
authors.forename: T
authors.initials: T
authors.lastname: Hlaing
mesh_terms: D000328:Adult; D000368:Aged; D000743:Anemia, Hemolytic / Q000150:complications* / Q000453:epidemiology; D018798:Anemia, Iron-Deficiency / Q000150:complications* / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D004909:Erythrocyte Indices; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006306:Health Surveys; D006454:Hemoglobins / Q000032:analysis*; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012423:Rural Health; D012727:Sex Characteristics; D014739:Victoria / Q000453:epidemiology
chemical_list: D006442:Glycated Hemoglobin; D006454:Hemoglobins; C517652:hemoglobin A1c protein, human