OBJECTIVE The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA_1c) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA_1c and other traditional risk factors in such patients.

RESEARCH DESIGN AND METHODS Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence.

RESULTS During a median follow-up of 8.88 years, 831 incidence cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA_1c, drug-related variables, and comorbidities, both FPG CV and HbA_1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06–1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11–1.58) for the third tertile in HbA_1c CV.

CONCLUSIONS FPG CV and HbA_1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA_1c CV can be valuable therapeutic targets for patients with T2DM at risk.