Identifying the independent effect of HbA1cvariability on adverse health outcomes in patients with Type 2 diabetes.
To characterize the relationship between HbA1cvariability and adverse health outcomes among US military veterans with Type 2 diabetes.



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 HbA1cvariability during a 3-year baseline period. HbA1cvariability, 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 HbA1ctests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA1clevels and the direction of change in HbA1clevels during the baseline period.



Over a mean 3.3 years of follow-up, all HbA1cvariability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA1cvariability, 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 HbA1clevels independently predicted the likelihood of each outcome.



In veterans with Type 2 diabetes, greater HbA1cvariability was associated with an increased risk of adverse long-term outcomes, independently of HbA1clevels and direction of change. Limiting HbA1cfluctuations over time may reduce complications.
VA Boston Healthcare System, Boston, MA, USA.|Boston University School of Medicine, Boston, MA, USA.
J C
JC
Prentice
VA Boston Healthcare System, Boston, MA, USA.|Northeastern University, Boston, MA, USA.
S D
SD
Pizer
VA Boston Healthcare System, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
P R
PR
Conlin
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000401:mortality; D057915:Drug Substitution / Q000706:statistics & numerical data; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D020521:Stroke / Q000401:mortality; D014481:United States / Q000453:epidemiology; D014728:Veterans
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin