Identifying the independent effect of HbA 1c variability on adverse health outcomes in patients with Type 2 diabetes

Diabet Med. 2016 Dec;33(12):1640-1648. doi: 10.1111/dme.13166. Epub 2016 Jul 17.


Aims: To characterize the relationship between HbA1c variability and adverse health outcomes among US military veterans with Type 2 diabetes.

Methods: This retrospective cohort study used Veterans Affairs and Medicare claims for veterans with Type 2 diabetes taking metformin who initiated a second diabetes medication (n = 50 861). The main exposure of interest was HbA1c variability during a 3-year baseline period. HbA1c variability, categorized into quartiles, was defined as standard deviation, coefficient of variation and adjusted standard deviation, which accounted for the number and mean number of days between HbA1c tests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA1c levels and the direction of change in HbA1c levels during the baseline period.

Results: Over a mean 3.3 years of follow-up, all HbA1c variability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA1c variability, the hazard ratios for the third and fourth quartile predicting mortality were 1.14 (95% CI 1.04, 1.25) and 1.42 (95% CI 1.28, 1.58), for myocardial infarction and stroke they were 1.25 (95% CI 1.10, 1.41) and 1.23 (95% CI 1.07, 1.42) and for ambulatory-care sensitive condition hospitalization they were 1.10 (95% CI 1.03, 1.18) and 1.11 (95% CI 1.03, 1.20). Higher baseline HbA1c levels independently predicted the likelihood of each outcome.

Conclusions: In veterans with Type 2 diabetes, greater HbA1c variability was associated with an increased risk of adverse long-term outcomes, independently of HbA1c levels and direction of change. Limiting HbA1c fluctuations over time may reduce complications.

Publication types

  • Observational Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetic Angiopathies / mortality
  • Drug Substitution / statistics & numerical data
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Myocardial Infarction / mortality
  • Prognosis
  • Retrospective Studies
  • Stroke / mortality
  • United States / epidemiology
  • Veterans


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Metformin