Mechanisms
Lp(a) raises cardiovascular risk in diabetes yet paradoxically low Lp(a) predicts developing diabetes in the first place, review by Corral's group finds (Curr Opin Lipidol 2025)
Original title: Are Lipoprotein(a) levels decreased in insulin resistance and type 2 diabetes?
This review by Corral, Matta and Schreier examines Lp(a)'s dual, seemingly contradictory role in cardiometabolic disease: large-scale studies confirm Lp(a) as a potent cardiovascular risk factor in type 2 diabetes, with the risk-relevant Lp(a) threshold actually lower in diabetic than non-diabetic individuals, while separate observational and genetic studies show an inverse relationship between Lp(a) and the risk of developing type 2 diabetes in the first place, linked to insulin dynamics, Kringle IV-type-2 repeat variants and metabolic pathways. The authors also note emerging links between Lp(a), non-alcoholic fatty liver disease and statin use, though Mendelian randomisation studies addressing causality have given conflicting results, leaving key mechanistic questions open. They conclude this paradox, low Lp(a) as a diabetes risk marker even as high Lp(a) drives cardiovascular risk, raises concerns about the metabolic consequences of aggressive Lp(a)-lowering therapy and calls for further research to guide its clinical use in diabetic patients.
Original abstract
Purpose Of Review: Lipoprotein(a) [Lp(a)] is a significant player in cardiovascular disease (CVD) and type 2 diabetes (T2D). While Lp(a) contributes to residual cardiovascular risk in T2D, lower levels paradoxically increase the risk of developing T2D. This review explores Lp(a)'s dual role in cardiometabolic disease, its association with T2D, and emerging Lp(a)-lowering therapies.
Recent Findings: Large-scale studies confirm Lp(a) as a potent risk factor for cardiovascular events in T2D, with lower Lp(a) thresholds increasing risk compared to nondiabetic individuals. Observational and genetic studies reveal an inverse relationship between Lp(a) and T2D risk, linked to insulin dynamics, Kringle IV-type-2 repeat variants, and metabolic pathways. Emerging evidence suggests a connection between Lp(a), nonalcoholic fatty liver disease, and statin use. However, Mendelian randomization analyses have yielded conflicting results, leaving key mechanistic questions unresolved.
Summary: Lp(a) plays a complex role in cardiometabolic health, acting as both a cardiovascular hazard and a potential metabolic marker in T2D. The paradoxical association of low Lp(a) with increased T2D risk challenges conventional perspectives and raises concerns regarding Lp(a)-lowering interventions. Further research is needed to clarify causality, refine risk stratification, and guide clinical decisions for Lp(a) modulation in T2D patients.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.