HbA1c variability associated with dementia risk in people with type 2 diabetes

Abstract 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.