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Small High-Density Lipoprotein (HDL) Subclasses are Increased with Decreased Activity of HDL-Associated Phospholipase A2 in Subjects with Prediabetes

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Lipids

Abstract

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A2 (HDL-LpPLA2) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA2.

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Abbreviations

ADA:

American Diabetes Association

apo:

Apolipoprotein

BMI:

Body mass index

CETP:

Cholesteryl ester transfer protein

CHD:

Coronary heart disease

CVD:

Cardiovascular disease

HDL:

High-density lipoprotein

HDL2:

Large high-density lipoprotein subclass

HDL3:

Small high-density lipoprotein subclass

HDL-C:

High-density lipoprotein cholesterol

HDL-LpPLA2 :

High-density lipoprotein-associated phospholipase A2

HOMA:

Homeostasis model assessment

IFG:

Impaired fasting glucose

IGT:

Impaired glucose tolerance

LCAT:

Lecithin: cholesterol acyltransferase

LDL-C:

Low-density lipoprotein cholesterol

Lp(a):

Lipoprotein a

LpPLA2 :

Lipoprotein-associated phospholipase A2

PON1:

Paraoxonase-1

Rf:

Retention factor

sdLDL-C:

Small dense low-density lipoprotein cholesterol

T2DM:

Type 2 diabetes mellitus

TAG:

Triacylglycerol

TC:

Total cholesterol

VLDL:

Very low-density lipoprotein

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Acknowledgments

The authors would like to thank the Atherothrombosis Research Centre of the University of Ioannina for providing access to the laboratory equipments and facilities.

Conflict of interest

This study was conducted independently; no company or institution supported it financially. Some of the authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies.

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Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, University of Ioannina, 45 110, Ioannina, Greece

    Theodosios D. Filippatos, Evangelos C. Rizos, Vasilios Tsimihodimos, Irene F. Gazi & Moses S. Elisaf

  2. Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece

    Alexandros D. Tselepis

Authors
  1. Theodosios D. Filippatos
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  2. Evangelos C. Rizos
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  3. Vasilios Tsimihodimos
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  4. Irene F. Gazi
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  5. Alexandros D. Tselepis
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  6. Moses S. Elisaf
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Correspondence to Moses S. Elisaf.

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Filippatos, T.D., Rizos, E.C., Tsimihodimos, V. et al. Small High-Density Lipoprotein (HDL) Subclasses are Increased with Decreased Activity of HDL-Associated Phospholipase A2 in Subjects with Prediabetes. Lipids 48, 547–555 (2013). https://doi.org/10.1007/s11745-013-3787-1

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  • DOI: https://doi.org/10.1007/s11745-013-3787-1

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