Lipoprotein (a) and diabetes mellitus

Abstract

Lp(a) and diabetes are both known and established risk factors for the development of cardiovascular disease. However, studies trying to link both risk factors find an inverse association between Lp(a) and risk of prevalent and incident diabetes. It is not yet clear though whether this association is causal and whether this possible causal link is due to Lp(a) concentration itself, to length of the apo(a) isoforms, or both. The results of Mendelian Randomisation studies are highly heterogeneous. This review aims to shed light on the most recent findings of epidemiological and Mendelian Randomisation studies and disentangle the contradictory results. Only part of the observed association of Lp(a) with diabetes can likely be explained by causality and may also be driven by reverse causation, co-morbidities, or medications. Furthermore, this review also summarizes the role of Lp(a) within patients with diabetes. Several studies suggest that elevated Lp(a) is a causal independent risk factor for CVD in patients. Although therapies that specifically target and lower Lp(a) have not been evaluated in diabetic patients, analysis of the large PCSK9 clinical outcomes trials suggest they are beneficial on cardiovascular outcomes.