Visit-to-visit variability of glycated hemoglobin (HbA1c) is a marker of long-term glycemic fluctuation, which has been related to increased risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM). The association between HbA1c variability and retinopathy in patients with T2DM, however, has been inconsistent in previous studies. In order to fully evaluate the above association, we conducted a meta-analysis. Observational studies related to the aim of the meta-analysis were identified by search of PubMed, Web of Science, and Embase databases. Studies with HbA1c variability evaluated as the standard deviation (SD) and/or the coefficients of variation (CV) of HbA1c were included. The results were analyzed using a random-effects model that incorporated potential heterogeneity between studies. Twelve observational studies involving 44 662 T2DM patients contributed to the meta-analysis. Overall, 5150 (11.5%) patients developed retinopathy. Pooled results showed that compared to patients with lower HbA1c variability, T2DM patients with higher HbA1c-SD (relative risk [RR]: 1.48, 95% confidence interval [CI]: 1.24 to 1.78, p<0.001, I2=34%) and higher HbA1c-CV (RR: 1.29, 95% CI: 1.05 to 1.59, p=0.02, I2=0%) were both associated with higher risk of DR. For studies with HbA1c-SD, the association was not significantly affected by study characteristics such as country, study design, mean age, disease duration, adjustment of mean HbA1c, or quality scores (p for subgroup difference all>0.05). In conclusion, higher HbA1c variability may be associated with an increased risk of retinopathy in patients with T2DM.

* These authors contributed equally to this work.

Received: 14 July 2022

Accepted after revision: 15 August 2022

Article published online:
12 October 2022

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