Long-Term Glycemic Variability and Risk of Cardiovascular Events in Type 2 Diabetes: A Meta-Analysis

Long-term glycemic fluctuation has been associated with cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, the findings are inconsistent. We performed a meta-analysis to summarize the association between parameters of long-term glycemic variability and risk of cardiovascular events in T2DM patients. Medline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of cardiovascular events in T2DM patients with higher or lower long-term glycemic variability. A random-effect model incorporating the potential heterogeneity among the included studies was used to pool the results. Twelve follow-up studies with 146 653 T2DM patients were included. The mean follow-up duration was 4.9 years. Pooled results showed that compared to those with the lowest glycemic variability, patients with the highest glycemic variability had significantly increased risk of cardiovascular events, as evidenced by the standard deviation of glycated hemoglobin [HbA1c-SD: relative risk (RR)=1.44, 95% confidence interval (CI): 1.23 to 1.69, p<0.001; I²=70%], HbA1c coefficient of variation (HbA1c-CV: RR=1.46, 95% CI: 1.19 to 1.79. p<0.001; I²=83%), standard deviation of fasting plasma glucose (FPG-SD: RR=1.33, 95% CI: 1.07 to 1.65, p=0.009; I²=0%), and FPG coefficient of variation (FPG-CV: RR=1.29, 95% CI: 1.01 to 1.64, p=0.04; I²=47%). In conclusion, increased long-term glycemic variability may be an independent risk factor for cardiovascular events in T2DM patients.