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

Abstract

Aims To characterize the relationship between HbA_1c 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 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. Results Over 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. Conclusions In 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.