RNA therapeutics
Lp(a) explains part of the residual vascular risk in diabetes, driving both macro- and microvascular damage, review argues (Int J Mol Sci 2025)
Original title: Diabetes Mellitus and Lipoprotein(a): A Determinant Interaction in Micro- and Macrovascular Damage
This review addresses why people with diabetes mellitus who meet their cholesterol goals still face elevated cardiovascular risk, pointing to lipoprotein(a) as a major, inherited contributor. Lp(a) resembles plasminogen closely enough to reduce plasmin formation and impair clot dissolution, while oxidation and glycation of the particle add vascular inflammation; concentrations above 30 mg/dL (75 nmol/L), and particularly above 50 mg/dL (125 nmol/L), are independently associated with coronary artery disease, ischaemic stroke, diabetic nephropathy, retinopathy and neuropathy. Conventional lipid-lowering therapies have neutral or modest effects on Lp(a), whereas RNA-based agents (antisense oligonucleotides and siRNAs) achieve reductions of 70 to 95% with consistent phase 2 results. The authors argue for at-least-once-in-a-lifetime Lp(a) measurement, especially in diabetic patients, to better plan treatment as targeted therapies mature, potentially improving both cardiovascular and microvascular outcomes.
Original abstract
Even when people with diabetes mellitus (DM) meet their cholesterol goals, they still face a higher risk of heart and blood vessel problems. One major reason is a particle called lipoprotein(a), or Lp(a), which is similar to LDL cholesterol. Raised levels of Lp(a) are inherited rather than caused by lifestyle. Lp(a) can build up in the body and make it easier for blood clots to form because it closely resembles a protein called plasminogen, reducing its ability to form plasmin that dissolves blood clots. At the same time, chemical changes like oxidation and glycation can make blood vessels more inflamed, adding to the risk. Elevated concentrations of Lp(a) (>30 mg/dL; 75 nmol/L), and particularly >50 mg/dL (125 nmol/L), are independently associated with coronary artery disease, ischemic stroke, diabetic nephropathy, retinopathy, and neuropathy. Conventional lipid-lowering therapies exert neutral or modest effects on Lp(a), in contrast to RNA-based targeted agents (antisense oligonucleotides and siRNA [Small Interfering RNA]), which achieve reductions of 70-95% and show consistent results in Phase 2 clinical trials. In this review, we bring together findings from laboratory research and clinical studies, and highlight why it is important to measure Lp(a) levels-at least once in a person's life, and especially in those with diabetes-to help doctors better assess risk and plan more effective treatments. In diabetic populations, the adaptation of Lp(a)-targeted therapies could redefine the management of residual risk and improve both cardiovascular and microvascular outcomes.
diabetesmechanismsRNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.