HbA_1c variability associated with dementia risk in people with type 2 diabetes

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A_1c (HbA_1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA_1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA_1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA_1c SD quintiles were associated with greater dementia hazard among those with a mean HbA_1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA_1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA_1c variability is associated with greater dementia risk, even among those with HbA_1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. Highlights: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A_1c (HbA_1c) variability and dementia risk. Greater HbA_1c variability was associated with greater dementia hazard. This was most evident among those with normal–low mean HbA_1c concentrations.