Hemoglobin A1c time-in-range, mortality, and diabetes complications in older adults with diabetes

INTRODUCTION: Hemoglobin A1c (A1c) treatment goals in older adults often consider life expectancy and comorbidities. A1c stability may also inform the risks of major outcomes. We studied the association of individualized A1c time-in-range (A1c TIR) with mortality and diabetes complications. RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study of patients with diabetes, 65 years or older, from the Department of Veterans Affairs (VA) and Kaiser Permanente (KP) from 2004 to 2018. Patients had at least four A1c tests during a 3-year baseline, and A1c TIR was calculated as the percentage of days when A1c levels were within patient-specific target ranges. We estimated associations among A1c TIR and mortality, cardiovascular, and microvascular outcomes using time to event models and instrumental variable (IV) models. RESULTS: We identified 386 287 VA patients and 24 885 KP patients with a mean age of 74.3 years (SD 5.8) and 72.3 years (SD 5.7), respectively. Among VA patients, when compared with higher A1c TIR (80-100%), lower A1c TIR (0% to <20%) was associated with increased mortality (HR, 1.22; 95% CI 1.20 to 1.23) and cardiovascular outcomes (HR, 1.10; 95% CI 1.07 to 1.13). IV models showed similar associations. Among KP patients, lower A1c TIR (0% to <20%) was associated with mortality (HR, 1.36; 95% CI 1.27 to 1.45). IV models showed associations with increased mortality and cardiovascular outcomes. Among both VA and KP patients, greater A1c time below and time above range were associated with increased mortality. CONCLUSIONS: A1c stability within patient-specific target ranges is associated with a lower risk of major adverse outcomes among older adults with diabetes.