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Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease

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Abstract

Coronary artery disease, the leading cause of death in the developed and developing countries, is prevalent in diabetes mellitus with 68% cardiovascular disease (CVD)-related mortality. Epidemiological studies suggested inverse correlation between HDL and CVD occurrence. Therefore, low HDL concentration observed in diabetic patients compared to non-diabetic individuals was thought to be one of the primary causes of increased risks of CVD. Efforts to raise HDL level via CETP inhibitors, Torcetrapib and Dalcetrapib, turned out to be disappointing in outcome studies despite substantial increases in HDL-C, suggesting that factors beyond HDL concentration may be responsible for the increased risks of CVD. Therefore, recent studies have focused more on HDL function than on HDL levels. The metabolic environment in diabetes mellitus condition such as hyperglycemia-induced advanced glycation end products, oxidative stress, and inflammation promote HDL dysfunction leading to greater risks of CVD. This review discusses dysfunctional HDL as one of the mechanisms of increased CVD risks in diabetes mellitus through adversely affecting components that support HDL function in cholesterol efflux and LDL oxidation. The dampening of reverse cholesterol transport, a key process that removes cholesterol from lipid-laden macrophages in the arterial wall, leads to increased risks of CVD in diabetic patients. Therapeutic approaches to keep diabetes under control may benefit patients from developing CVD.

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Acknowledgements

The author would like to thank Maurizio Averna, University of Palermo, Palermo, Italy and Charles L Bisgaier, Gemphire Therapeutics, Livonia, MI, USA for many stimulating discussions relating to dysfunctional HDL, diabetes, and atherosclerosis.

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  1. Rai Ajit K. Srivastava

    Present address: Department of Pharmacology, Gemphire Therapeutics, 17199 Laurel Park, Livonia, MI, USA

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    Rai Ajit K. Srivastava

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During the preparation of this manuscript, the Rai Ajit K. Srivastava served as a consultant to Gemphire Therapeutics and currently employed at Gemphire Therapeutics Inc. The author has no conflict of interest.

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Srivastava, R.A.K. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Mol Cell Biochem 440, 167–187 (2018). https://doi.org/10.1007/s11010-017-3165-z

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