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Lipoproteins in Diabetes Mellitus pp 141–155Cite as

Lipoprotein(a): Structure, Metabolism, and Pathophysiology

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Part of the book series: Contemporary Diabetes ((CDI))

Abstract

Recent reports on large prospective epidemiological studies strongly suggest that Lp(a) is one of the strongest risk factor for atherosclerosis and myocardial infarction and that the association might be causal. Lp(a) belongs to the cholesterol ester-rich apoB-containing lipoproteins, yet its metabolism is distinct from that of LDL. Details of apo(a) metabolism slowly begin to unravel, and it was shown recently that apo(a) transcription is driven by a direct repeat in the apo(a) promoter that binds HNF4a. Activation of FXR on the other hand by bile salts or synthetic FXR ligands strikingly interferes with apo(a) transcription and biosynthesis. On the other hand, the question of the site of the assembly of Lp(a) from LDL and apo(a) is still unresolved. Despite the fact that Lp(a) binds to several specific lipoprotein receptors in vitro, their role for the in vivo metabolism remains to be established.

Lp(a) plasma concentrations are influenced by numerous factors. Genetic factors in the gene of apo(a) but also of other apolipoproteins strongly influence Lp(a) levels. In fact plasma Lp(a) is to >90 % inherited where the best studied kringle-4 size polymorphism accounts for >50 % of inheritance. Other factors like steroid hormones, dietary fatty acids, and vitamins have minor effects on Lp(a) levels. Concerning secondary factors, we know that kidney diseases cause a two- to threefold increase of Lp(a), whereas liver disease is mostly associated with grossly reduced plasma Lp(a) levels.

There are numerous reports in the literature where Lp(a) has been studied in individuals with type 1 and type 2 diabetes mellitus. The data are inconsistent and not easy to interpret. In type 1 diabetes mellitus (IDDM), Lp(a) plasma concentrations appear to be not altered as long as the patients are metabolically well controlled. However, Lp(a) of >30 mg/dl contributes significantly to the cardiovascular risk in this patient group. This appears to be in contrast to type 2 diabetes mellitus (NIDDM). A recent study on a large population reports that plasma Lp(a) is inversely related to type 2 diabetes mellitus and not responsible for the increased coronary artery disease risk in this group of patients.

Few therapeutic options exist in patients with increased plasma Lp(a). One is nicotinic acid or its derivatives that reduce Lp(a) by up to 35 %. Newer drugs, however, are in the pipeline and their safety and efficacy needs to be proven in ongoing clinical trials.

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Authors and Affiliations

  1. Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Alicia J. Jenkins

  2. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

    Alicia J. Jenkins

  3. University of Queensland, Mater Hospital, Brisbane, Australia

    Karam M. Kostner

  4. Medical University of Graz, Graz, Austria

    Gerhard M. Kostner

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  2. Karam M. Kostner
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Correspondence to Alicia J. Jenkins .

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Editors and Affiliations

  1. NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia

    Alicia J. Jenkins

  2. College of Medicine, University of Illinois, Peoria, Illinois, USA

    Peter P. Toth

  3. Section of Endocrinology and Diabetes Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Timothy J. Lyons

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Jenkins, A.J., Kostner, K.M., Kostner, G.M. (2014). Lipoprotein(a): Structure, Metabolism, and Pathophysiology. In: Jenkins, A., Toth, P., Lyons, T. (eds) Lipoproteins in Diabetes Mellitus. Contemporary Diabetes. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-7554-5_7

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