Identifying the independent effect of HbA1c variability on adverse health outcomes in patients with Type 2 diabetes

AimsTo characterize the relationship between HbA(1c) variability and adverse health outcomes among US military veterans with Type 2 diabetes. MethodsThis 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 HbA(1c) variability during a 3-year baseline period. HbA(1c) 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 HbA(1c) tests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA(1c) levels and the direction of change in HbA(1c) levels during the baseline period. ResultsOver a mean 3.3 years of follow-up, all HbA(1c) variability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA(1c) 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 HbA(1c) levels independently predicted the likelihood of each outcome. ConclusionsIn veterans with Type 2 diabetes, greater HbA(1c) variability was associated with an increased risk of adverse long-term outcomes, independently of HbA(1c) levels and direction of change. Limiting HbA(1c) fluctuations over time may reduce complications.