Lipoprotein-associated phospholipase A2 (Lp-PLA2): a novel biomarker for diabetic neuropathy?

Aims: Lipoprotein-associated phospholipase A2 (Lp-PLA2) – an enzyme associated with inflammation and oxidative stress, has been previously shown to be related to poor cardiovascular outcomes especially in diabetes. This study, for the first time, examines the relationship between Lp-PLA2 and diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2DM).

Methods: This is a retrospective study of 880 T2DM hospital patients studied between 03/24 and 08/24. DPN was assessed based on clinical symptoms and along with one abnormal finding from five tests: ankle reflexes, pinprick sensation, vibration perception, temperature perception, or pressure perception (or two abnormalities among these tests in patients without clinical symptoms). Non-diabetic neuropathy was excluded. Subjects were divided into four quartiles based on Lp-PLA2 levels. Multiple logistic regression model and receiver operating characteristic (ROC) curve were used.

Results: DPN exhibited elevated Lp-PLA2 levels compared to those without DPN. Even after adjusting for multiple variables, Lp-PLA2 was independently associated with a higher likelihood of DPN (odds ratio [OR] 1.011, 95 % confidence interval [CI] 1.008–1.014, P < 0.001). In ROC curve analysis, the area under the curve (AUC) for Lp-PLA2 was 0.664, while the combined indicator (incorporating Lp-PLA2 with additional clinical variables) AUC was 0.739.

Conclusions: The above findings suggest that Lp-PLA2 could serve as a valuable biomarker for identifying patients at risk for DPN.

Comments: The reason for bringing this study up is because I was not aware of Lp-PLA2 as a biomarker for DPN. The study has its own caveats including being done in hospitalised patients, only T2DM and DPN diagnosis based on clinical and bed side assessments which may underdiagnose the total burden. Medline search only revealed the role of Lp-PLA2 in renal microangiopathy and that fenofibrate reduces its levels (FIELD study).

Sanjeev Sharma

Reference: He Y, Ye M, Shen Z, Zhong Z, Xia Y, Li Q. Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study. J Diabetes Complications. 2025 Jan 14;39(2):108950. doi: 10.1016/j.jdiacomp.2025.108950. Epub ahead of print. PMID: 39817931.

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