Association between visit-to-visit variability of HbA1c and cognitive decline: a pooled analysis of two prospective population-based cohorts
The aim of this study was to investigate the association between visit-to-visit variability in HbA1c and cognitive function decline in the elderly population.
We performed a pooled analysis of two prospective population-based cohorts (the Health Retirement Study [HRS] and the English Longitudinal Study of Ageing [ELSA]). Cognitive function, including memory and executive function, were assessed at baseline and every 2 years, while HbA1c levels were assessed at baseline and every 4 years. Visit-to-visit variability (VVV) in HbA1c was calculated using the CV, SD and variation independent of the mean (VIM) during the follow-up period. Linear mixed models were used to evaluate the association between HbA1c variability and cognitive function decline with adjustment for demographics, mean HbA1c, education, smoking, alcohol consumption, BMI, baseline hypertension, baseline diabetes status and HDL-cholesterol.
The study enrolled 6237 participants (58.23% women, mean age 63.38 ± 8.62 years) with at least three measurements of HbA1c. The median follow-up duration was 10.56 ± 1.86 years. In the overall sample, compared with the lowest quartile of HbA1c variability, participants in the highest quartile of HbA1c variability had a significantly worse memory decline rate (−0.094 SD/year, 95% CI −0.185, −0.003) and executive function decline rate (−0.083 SD/year, 95% CI −0.125, −0.041), irrespective of mean HbA1c values over time. Among individuals without diabetes, each 1-SD increment in HbA1c CV was associated with a significantly higher rate of memory z score decline (−0.029, 95% CI −0.052, −0.005) and executive function z score decline (−0.049, 95% CI −0.079, −0.018) in the fully adjusted model.
We observed a significant association between long-term HbA1c variability and cognitive decline among the non-diabetic population in this study. The effect of maintaining steady glucose control on the rate of cognitive decline merits further investigation.
KeywordsCognitive decline Cognitive function Epidemiology Glucose variability HbA1c
English Longitudinal Study of Ageing
Health and Retirement Study
Multiple imputation of chained equation
Variation independent of the mean
We thank the University of Michigan for the use of data from the HRS Waves 8–13 from 2006–2016 and the UK Data Archive for the use of data from the ELSA Waves 2–7 from 2002–2015. The original data creators, depositors or copyright holders bear no responsibility for the current analysis or interpretation.
KC is the guarantor of this work and had full access to all of the data in the study. KC and ZY conceptualised the study and designed the analysis plan. ZY performed all the statistical analyses and drafted the manuscript. JW provided supervision to ZY. All authors contributed to the acquisition, analysis or interpretation of data; provided critical revision of the manuscript for important intellectual content and approved the final version. KC is responsible for the integrity of the work as a whole.
The HRS data are sponsored by the National Institute on Aging (grant number U01AG009740), and the study is being conducted by the University of Michigan. The current study was funded by the Ministry of Science and Technology of the People’s Republic of China (No. 2015FY111600). The funders played no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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