Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study

OBJECTIVEThe 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 METHODSPatients 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.RESULTSDuring a median follow-up of 8.88 years, 831 incident 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.CONCLUSIONSFPG 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.