Abstract
OBJECTIVE: This systematic review aimed to assess whether lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of complications in patients with diabetes mellitus (DM). METHODS: We searched PubMed, Embase, Web of Science, and Scopus databases for studies fulfilling the inclusion criteria till 30 June 2025. The relationship between Lp-PLA2 and cardiovascular disorders (CVD), diabetic kidney disease (DKD), diabetic retinopathy (DR), diabetic neuropathy (DN), and lower extremity arterial disease (LEAD) was assessed using a qualitative and quantitative analysis. RESULTS: Twelve studies were included. The majority of studies were on DKD. Pooled analysis showed that high Lp-PLA2 was associated with significantly higher risk of DKD (OR: 1.01 95% CI: 1.01, 1.02 I(2) = 93%) but not for CVD (OR: 1.11 95% CI: 0.97, 1.26 I(2) = 88%), DN (OR: 2.02 95% CI: 0.40, 10.23 I(2) = 88%) or DR (OR: 1.28 95% CI: 0.49, 3.34 I(2) = 96%). Sensitivity analysis revealed non-significant results for DKD and CVD. Subgroup analysis for DKD showed that heterogeneity reduced to zero in cross-sectional studies, among those with <30% prevalence of DKD, and among those reporting adjusted data, but results also became non-significant across multiple subgroups. CONCLUSIONS: Limited evidence indicates that high Lp-PLA2 may be predictive of DKD in DM patients. However, the strength of the association is too low and the finding may not be relevant for clinical application. Lp-PLA2 was not found to predict CVD, DN, or DR, but with very scarce data. The high heterogeneity and non-significant results on sensitivity analysis limits the strength of the evidence. More robust studies are required to supplement the present evidence. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, PROSPERO CRD420251069254.