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

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.

Glucose fluctuations aggravate myocardial fibrosis via activating the CaMKII/Stat3 signaling in type 2 diabtetes

“…Glycemic management in diabetic patients is now focused not only on effective glucose reduction, but also on how to avoid glucose fluctuations [ 1 ]. Our previous studies have shown that glucose fluctuations contribute to the development of many cardiovascular diseases [ 5 , 24 ]. More importantly, GF in type 1 diabetes can lead to increased myocardial fibrosis [ 6 ], but the pathophysiological mechanisms contributing to GF-induced myocardial fibrosis remain elusive, especially in type 2 diabetes.…”

“…Glucose fluctuations, also known as glucose variability, are developing as an emerging indicator of glycemic control [ 1 , 2 ]. Previous studies have shown that a higher GF is independently associated with heart failure [ 3 ], arrhythmias [ 4 ], and cardiovascular events [ 5 ]. In type 1 diabetes, GF can lead to myocardial fibrosis [ 6 ]; however, there is currently limited understanding of whether GF can lead to myocardial fibrosis in type 2 diabetes and the mechanisms involved have not been clarified.…”

Serum Cytokines and Growth Factors in Subjects with Type 1 Diabetes: Associations with Time in Ranges and Glucose Variability

“…A recent analysis of 14 studies with 254,017 patients with diabetes revealed that the highest HbA1c variability is associated with increased risks of CVD. The CVD risk associated with HbA1c variability might be even higher among patients with T1D [12]. However, the role of short-term GV as a trigger of diabetic complications remains to be clarified.…”