Clinical impact of variability in HbA1c as assessed by simultaneously measuring fructosamine and use of error grid analysis

Ann Clin Biochem. 2008 Jul;45(Pt 4):421-5. doi: 10.1258/acb.2008.007259.


Background: Haemoglobin A1c (HbA1c) is the only measure of glycaemic control used for many patients with diabetes, but it has limitations and might sometimes be misleading. HbA(1c) concentrations are influenced by conditions that alter red-cell life and there is evidence that biochemical variation in intracellular glycation rates also influence HbA1c concentrations. This paper is the first to propose a method of using simultaneously measured HbA1c and fructosamine, and error grid analysis, in the clinical setting, to gain a better understanding of glycaemic control.

Methods: Cross-sectional analytical study using HbA1c and fructosamine measures on the same blood sample from 1744 patients having blood taken for hospital diabetes clinic appointments. No other selection or exclusion criteria were applied.

Results: The fructosamine results were converted to a HbA1c equivalent which was then compared with the HbA1c. In an Altman-Bland plot, the paired result differences ranged between -6.9% and +5.5% HbA1c with 1139 (65%), 438 (25%), 130 (8%) and 37 (2%) being < or =1%, 1-2%, 2-3% or >3% of HbA1c difference, respectively. In clinical error grid analysis, 864 (50%) results had tight concordance for clinical interpretation, 761 (43%) had one block disunity of probably little clinical significance, but 105 (6%) were two blocks and 14 (1%) were three blocks discordant.

Conclusion: HbA1c may not accurately reflect glucose control. Our method, utilizing co-assessment with serum fructosamine, evaluates the possible clinical impact of this. We suggest the analysis used in this paper should be used routinely in diabetes practice.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / metabolism
  • Female
  • Fructosamine / blood*
  • Glycated Hemoglobin A / analysis*
  • Humans
  • Male
  • Middle Aged
  • Sensitivity and Specificity
  • Time Factors


  • Blood Glucose
  • Glycated Hemoglobin A
  • Fructosamine