Is inverse association between lipoprotein(a) and diabetes mellitus another paradox in cardiometabolic medicine?

ABSTRACT

Introduction

The impact of Type II Diabetes mellitus (T2DM) on cardiovascular disease (CVD) is well-established, while lipoprotein(a) [Lp(a)] has recently emerged as a recognized CVD risk factor. The rising prevalence of T2DM resulting from modern lifestyles and the development of specific Lp(a)-lowering agents brought the association between T2DM and Lp(a) in the forefront.

Areas covered

Despite advancements in T2DM treatment, diabetic patients remain at very-high risk of CVD. Lp(a) may, to some extent, contribute to the persistent CVD risk seen in diabetic patients, and the coexistence of T2DM and elevated Lp(a) levels appears to synergistically amplify overall CVD risk. The relationship between T2DM and Lp(a) is paradoxical. On one hand, high Lp(a) plasma concentrations elevate the risk of diabetic microvascular and macrovascular complications. On the other hand, low Lp(a) plasma concentrations have been linked to an increased risk of developing T2DM.

Expert opinion

Comprehending the association between T2DM and Lp(a) is critical due to the pivotal roles both entities play in overall CVD risk, as well as the unique aspects of their relationship. The mechanisms underlying the inverse association between T2DM and Lp(a) remain incompletely understood, necessitating further meticulous research.

KEYWORDS:

• Cardiovascular disease risk factors
• lipoprotein(a)
• type 2 diabetes mellitus
• T2DM-Lp(a) synergistic effect
• T2DM-Lp(a) paradox

Article highlights

• Patients with T2DM remain in very-high CVD risk despite the optimal disease control they may have.

• Lp(a) may be partly responsible for the residual risk observed in T2DM.

• T2DM and Lp(a) increase CVD risk in a synergistic way.

• Low Lp(a) concentration has been linked to an increased risk of T2DM development.

• The mechanisms explaining this paradoxical reverse association are yet to be clarified.

Declaration of interest

LS Rallidis has received research grants and honoraria from Amgen, Sanofi-Aventis, Viatris, Novartis, Vianex and Servier, outside the submitted work.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.