High Glycemic Variability Linked to Increased PAD Risk: Study
Researchers have found in a new study that elevated long-term glycemic variability (GV) is associated with a higher risk of peripheral artery disease (PAD). However substantial heterogeneity among studies warrants cautious interpretation of the strength of this association. The study was conducted by Jie Xia and colleagues.
To elucidate the relationship between glucose variability and PAD, a meta-analysis prospectively registered in PROSPERO with ID number CRD420251148763 was performed. Researchers systematically searched PubMed, Embase, and Web of Science databases to retrieve relevant studies on longitudinal cohort studies reporting long-term glycemic variability and PAD outcomes. Risk ratio (RR) was calculated as the primary endpoint comparing high versus low glycemic variability among participants.
Risk estimates were pooled using random-effects models, considering differences among included studies. Researchers tested the consistency of risk estimates among pre-specified subgroups. Potential subgroups include geographic region (Asian vs Western populations), study design, diabetes, type of glycemic variability, definition of PAD, HbA1c adjustment, and total follow-up period.
Key findings:
- An increased long-term glucose variability was significantly related to a higher probability of peripheral artery disease (RR: 1.42; 95% CI [1.21-1.66], p < 0.001).
- There was a significant amount of statistical heterogeneity in the included cohorts (I² = 91%), which implies that there is a difference in effect size between the included studies.
- The positive relationship was maintained across all subgroups stratified by geographic location, study design, diabetes status, variability measures, method of disease diagnosis, and adjusting for HbA1c (all p for subgroup differences > 0.05).
- The length of follow-up had a significant effect on the strength of the relationship (p for subgroup differences = 0.006), with studies having less than 8 years of follow-up having a higher effect size (RR: 1.64) than those with 8 years or more of follow-up (RR: 1.19).
The above findings suggest that there is a high risk of peripheral artery disease as a result of elevated long-term glucose variability in various patient groups. The findings of this study clearly point out that even though glucose variability might be used as a predictor of risk, there is some heterogeneity and observational studies that affect the degree of uncertainty of causality and its size.
Reference:
Xia, Jie & Peng, Qionghui & Chen, Lei & Liu, Chiqiong & Zhu, Ting. (2026). Long-term glycemic variability and risk of peripheral artery disease: a systematic review and meta-analysis of cohort studies. PeerJ. 14. e21686. 10.7717/peerj.21686.
