Higher glucose fluctuation is associated with a higher risk of cardiovascular disease: Insights from pooled results among patients with diabetes

Document Type

Article

Publication Date

5-1-2023

Abstract

Background: The relationship between glucose fluctuation and the risk of cardiovascular disease (CVD) in patients with diabetes remains elusive. Glycated hemoglobin (HbA1c) variability is a key parameter of glucose fluctuation. Methods: PubMed, Cochrane Library, Web of Science, and Embase were searched up to 1 July 2022. Studies reporting associations of HbA1c variability (HbA1c-SD), coefficient of variation of HbA1c (HbA1c-CV), and HbA1c variability score [HVS] with the risk of CVD among patients with diabetes were included. We used three different insights (a high-low value meta-analysis, a study-specific meta-analysis, and a non-linear dose–response meta-analysis) to explore the relationship between HbA1c variability and CVD risk. A subgroup analysis was also performed to screen the potential confounding factors. Results: A total of 14 studies with 254 017 patients with diabetes were eligible. The highest HbA1c variability was significantly associated with increased risks of CVD (HbA1c-SD, risk ratio [RR] 1.45; HbA1c-CV, RR 1.74; HVS, RR 2.46; all p <.001) compared to the lowest HbA1c variability. The RRs of CVD for per HbA1c variability were significantly >1 (all p <.001). The subgroup analysis for per HbA1c-SD found a significant exposure-covariate interaction in the types of diabetes (p =.003 for interaction). The dose–response analysis showed a positive association between HbA1c-CV and CVD risk (P for nonlinearity <.001). Conclusions: Our study suggests that the higher glucose fluctuation is significantly associated with the higher CVD risk in diabetes patients based on HbA1c variability. The CVD risk associated with per HbA1c-SD might be higher among patients type 1 diabetes than patients with type 2 diabetes.

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