Association of hemoglobin A1c stability with mortality and diabetes complications in older adults with diabetes

INTRODUCTION: Hemoglobin A1c (A1c) treatment goals in older adults should be individualized to balance risks and benefits. It is unclear if A1c stability over time within unique target ranges also affects adverse outcomes. RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study from 2004 to 2016 of veterans with diabetes and at least four A1c tests during a 3-year baseline. We generated four distinct categories based on the percentage of time that baseline A1c levels were within patient-specific target ranges: ≥60% time in range (TIR), ≥60% time below range (TBR), ≥60% time above range (TAR), and a mixed group with all times <60%. We assessed associations of these categories with mortality, macrovascular, and microvascular complications. RESULTS: We studied 397 634 patients (mean age 76.9 years, SD 5.7) with an average of 5.5 years of follow-up. In comparison to ≥60% A1c TIR, mortality was increased with ≥60% TBR, ≥60% TAR, and the mixed group, with HRs of 1.12 (95% CI 1.11 to 1.14), 1.10 (95% CI 1.08 to 1.12), and 1.06 (95% CI 1.04 to 1.07), respectively. Macrovascular complications were increased with ≥60% TBR and ≥60% TAR, with estimates of 1.04 (95% CI 1.01 to 1.06) and 1.06 (95% CI 1.03 to 1.09). Microvascular complications were lower with ≥60% TBR (HR 0.97, 95% CI 0.95 to 1.00) and higher with ≥60% TAR (HR 1.11, 95% CI 1.08 to 1.14). Results were similar with higher TIR thresholds, shorter follow-up, and competing risk of mortality. CONCLUSIONS: In older adults with diabetes, mortality and macrovascular complications are associated with increased time above and below individualized A1c target ranges. Higher A1c TIR may identify patients with lower risk of adverse outcomes.