Association between HbA1c variability and mortality in patients with type 2 diabetes

J Diabetes Complications. Jul-Aug 2014;28(4):494-9. doi: 10.1016/j.jdiacomp.2014.02.006. Epub 2014 Feb 18.


Aims: We aimed to evaluate the association between HbA1c variability and mortality due to all causes, cancer, and non-cancer in patients with type 2 diabetes independently of mean HbA1c levels.

Methods: We enrolled 754 patients with type 2 diabetes who first visited our hospital between 1995 and 1996, had been followed for at least 2years, and had undergone four or more HbA1c determinations. Patients were followed through June 2012. The standard deviation (SD) or coefficient of variation (CV) was used as a measure of HbA1c variability. Risk of death was evaluated by multivariate Cox proportional hazard models.

Results: Through June 2012, 63 patients died. Hazard ratios (HRs) for all-cause mortality and non-cancer mortality including cardiovascular diseases (CVD) increased across tertiles of both HbA1cSD and HbA1cCV. HRs for cancer mortality did not increase across tertiles of either HbA1cSD or HbA1cCV. Using a stepwise regression method, both HbA1cSD and HbA1cCV predicted all-cause mortality, especially non-cancer mortality. In contrast, mean HbA1c predicted cancer mortality.

Conclusions: HbA1c variability is a predictor of all-cause mortality, especially non-cancer mortality including CVD, in patients with type 2 diabetes, independent of mean HbA1c level. In contrast, mean HbA1c, but not HbA1c variability, might predict cancer mortality.

Keywords: All-cause mortality; Cancer mortality; HbA1c variability; Non-cancer mortality; Type 2 diabetes.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / mortality
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetic Angiopathies / mortality
  • Diabetic Cardiomyopathies / mortality
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / analysis*
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Mortality
  • Neoplasms / complications
  • Neoplasms / mortality
  • Outpatient Clinics, Hospital
  • Proportional Hazards Models
  • Reproducibility of Results
  • Retrospective Studies


  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human