Variables involved in the discordance between HbA1c and fructosamine: the glycation gap revisited

PLoS One. 2013 Jun 12;8(6):e66696. doi: 10.1371/journal.pone.0066696. Print 2013.

Abstract

Aims: Glycation gap (GG) is defined as the difference between the measured level of HbA1c and the level that would be predicted from its regression on the fructosamine level. The aims of the study were: 1) To determine the reproducibility and consistency of GC; 2) To discover factors related to GG value. Given that metformin might increase glucose transport through the erythrocyte membrane, this treatment was also considered in the analyses of the results.

Methods: GG was calculated in two blood samples separated 30.6 (SD 7.3) weeks, obtained in 508 type 2 diabetic patients. The following variables were considered: HbA1c, fructosamine, glucose, creatinine, hematological parameters and treatment with metformin. Multivariate and logistic regression analyses were performed to explore the variables independently related to CG.

Results: GG was reproducible and consistent over time. Creatinine, mean corpuscular hemoglobin concentration (MCHC), and glycemia (inverse relationship); and HbA1c and treatment with metformin (direct relationship) were independently related to GG. Patients treated with metformin showed higher HbA1c values, despite similar fructosamine concentrations, than patients not treated with the drug.

Conclusions: GG is independently related to serum levels of creatinine, MCHC and treatment with metformin. The spurious effect of metformin on Hb glycation could have serious clinical implications and should be considered when interpreting the results of clinical trials.

MeSH terms

  • Analysis of Variance
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Fructosamine / blood*
  • Glycated Hemoglobin / metabolism*
  • Glycosylation / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Logistic Models
  • Metformin / pharmacology
  • Spain

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Fructosamine
  • Metformin
  • Creatinine

Grants and funding

The authors have no support or funding to report.