Abstract
Background Variability of HbA1c has been related to the incidence micro and macrovascular complications in patients with diabetes. However, the association between of visit-to-visit variability of HbA1c and risk of dementia has not been fully determined. A meta-analysis was performed to comprehensively evaluate the above association. Methods Medline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of dementia in diabetic patients with higher or lower variability of HbA1c. A random-effect model incorporating the potential heterogeneity among the included studies were used to pool the results. Results Five retrospective studies with 577592 diabetic patients were included, and 99% of them were with type 2 diabetes mellitus (T2DM). With a mean follow-up duration of 6.3 years, 31963 patients had newly diagnosed dementia. Pooled results showed that diabetic patients with higher HbA1c variability was associated with higher risk of dementia, as evidenced by studies with coefficient of variation (CV: hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.003–1.120; p=0.04; I2 = 47%) and standard deviation (SD : HR: 1.19; 95% CI: 1.06–1.32; p=0.002; I2 = 0%) of HbA1c in continuous variables, and CV of HbA1c (HR: 1.18; 95% CI: 1.08–1.28; p < 0.001; I2 = 31%) in categorized variables. Conclusions Higher variability of HbA1c is associated with a higher incidence of dementia in patients with diabetes.
Highlights
Accumulating evidence suggests that diabetes may be a risk factor for cognitive impairment, and diabetes has been associated with higher risk of dementia [1,2,3]
Subsequent studies demonstrated that besides persistent hyperglycemia, episodes of hypoglycemia associated with antidiabetic treatments are associated with some adverse events and complications in patients with diabetes, including cognitive impairment [6, 7]
768 articles were found via initial literature search of PubMed, Embase, and Web of Science databases after excluding of the duplication, and 742 were further excluded through screening of the titles and abstracts mainly because they were not relevant to the purpose of the meta-analysis
Summary
Accumulating evidence suggests that diabetes may be a risk factor for cognitive impairment, and diabetes has been associated with higher risk of dementia [1,2,3]. Previous studies have suggested that increased HbA1c variability, calculated as coefficient of variation (CV) or standard deviation (SD) of visit-to-visit HbA1c, may be independently associated with higher risk of vascular complications in patients with diabetes [13, 14]. It remains not fully determined whether HbA1c variability is associated with a higher risk of dementia in diabetic patients [15,16,17,18,19]. Higher variability of HbA1c is associated with a higher incidence of dementia in patients with diabetes
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