Advertisement

CETP activity is not associated with carotid intima-media thickness in patients with poorly controlled type 2 diabetes

  • Benjamin BouilletEmail author
  • T. Gautier
  • B. Terriat
  • L. Lagrost
  • B. Verges
  • J. M. Petit
Original Article
  • 20 Downloads

Abstract

Aim

The impact of cholesteryl ester transfer protein (CETP) on atherosclerotic development in humans remains unclear. Plasma cholesteryl ester transfer was shown to be associated with carotid intima-media thickness in type 2 diabetic (T2D) patients with adequate metabolic control. Since glycation of CETP may influence cholesteryl ester transfer processes, it is important to determine if plasma cholesteryl ester transfer is still a determinant of carotid intima-media thickness (IMT) in patients with poorly controlled diabetes. The aim of the present study was to determine whether CETP activity influences carotid IMT in T2D patients with poor metabolic control.

Methods

In 110 individuals with T2D, we measured CETP mass concentration with ELISA, CETP activity with a radioactivity method and carotid intima-media thickness with high-resolution real-time B-mode ultrasonography.

Results

The mean HbA1C was 8.8 ± 1.7%. Carotid IMT did not correlate with CETP activity in the total population. In T2D patients with HbA1C < 8% (n = 33), mean HbA1C was 6.9% and the correlation between carotid IMT and CETP activity was not significant (p = 0.09). In a multivariable analysis that included the total population, carotid intima-media thickness was positively associated with diabetes duration (p = 0.02) but not with CETP activity or HbA1C.

Conclusions

We observed no correlation between carotid intima-media thickness, a marker of early atherosclerosis, and CETP activity in T2D patients with poor metabolic control. Disease duration, which reflects accumulated metabolic abnormalities, may have blunted the potential effect of CETP on atherosclerosis. Metabolic control appears essential to determine the pro- or anti-atherogenic influence of CETP in patients with T2D.

Keywords

Cholesteryl ester transfer protein Intima-media thickness Type 2 diabetes 

Notes

Acknowledgements

This work was supported by the Centre Hospitalier Universitaire de Dijon (AOI 2011), and proofreading services were provided by Suzanne Rankin (DRCI). We thank Dr. Serge Aho for his help in complementary statistical analyses.

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest

Ethical approval

All procedures performed in the study were in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all patients before inclusion.

References

  1. 1.
    Barter PJ, Nicholls SJ, Kastelein JJP, Rye K-A (2015) Is cholesteryl ester transfer protein inhibition an effective strategy to reduce cardiovascular Risk? CETP inhibition as a strategy to reduce cardiovascular risk: the pro case. Circulation 132(5):423–432CrossRefGoogle Scholar
  2. 2.
    Clark RW, Sutfin TA, Ruggeri RB et al (2004) Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler Thromb Vasc Biol 24(3):490–497CrossRefGoogle Scholar
  3. 3.
    de Vries R, Perton FG, Dallinga-Thie GM et al (2005) Plasma cholesteryl ester transfer is a determinant of intima-media thickness in type 2 diabetic and nondiabetic subjects: role of CETP and triglycerides. Diabetes 54(12):3554–3559CrossRefGoogle Scholar
  4. 4.
    Kahri J, Syvänne M, Taskinen MR (1994) Plasma cholesteryl ester transfer protein activity in non-insulin-dependent diabetic patients with and without coronary artery disease. Metabolism 43(12):1498–1502CrossRefGoogle Scholar
  5. 5.
    Riemens SC, van Tol A, Sluiter WJ, Dullaart RP (1999) Plasma phospholipid transfer protein activity is lowered by 24-h insulin and acipimox administration: blunted response to insulin in type 2 diabetic patients. Diabetes 48(8):1631–1637CrossRefGoogle Scholar
  6. 6.
    Passarelli M, Catanozi S, Nakandakare ER et al (1997) Plasma lipoproteins from patients with poorly controlled diabetes mellitus and « in vitro » glycation of lipoproteins enhance the transfer rate of cholesteryl ester from HDL to apo-B-containing lipoproteins. Diabetologia 40(9):1085–1093CrossRefGoogle Scholar
  7. 7.
    Gautier T, Masson D, de Barros JP et al (2000) Human apolipoprotein C-I accounts for the ability of plasma high density lipoproteins to inhibit the cholesteryl ester transfer protein activity. J Biol Chem 275(48):37504–37509CrossRefGoogle Scholar
  8. 8.
    Zeller M, Masson D, Farnier M et al (2007) High serum cholesteryl ester transfer rates and small high-density lipoproteins are associated with young age in patients with acute myocardial infarction. J Am Coll Cardiol 50(20):1948–1955CrossRefGoogle Scholar
  9. 9.
    Guyard-Dangremont V, Lagrost L, Gambert P, Lallemant C (1994) Competitive enzyme-linked immunosorbent assay of the human cholesteryl ester transfer protein (CETP). Clin Chim Acta Int J Clin Chem 231(2):147–160CrossRefGoogle Scholar
  10. 10.
    Lorenz MW, Price JF, Robertson C et al (2015) Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration. Diabetes Care 38(10):1921–1929CrossRefGoogle Scholar
  11. 11.
    Yamasaki Y, Kodama M, Nishizawa H et al (2000) Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease. Diabetes Care 23(9):1310–1315CrossRefGoogle Scholar
  12. 12.
    Yamasaki Y, Kawamori R, Matsushima H et al (1994) Atherosclerosis in carotid artery of young IDDM patients monitored by ultrasound high-resolution B-mode imaging. Diabetes 43(5):634–639CrossRefGoogle Scholar
  13. 13.
    Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (2003) Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc 23(2):160–167CrossRefGoogle Scholar
  14. 14.
    Alssema M, Dekker JM, Kuivenhoven JA et al (2007) Elevated cholesteryl ester transfer protein concentration is associated with an increased risk for cardiovascular disease in women, but not in men, with Type 2 diabetes: the Hoorn Study. Diabet Med 24(2):117–123CrossRefGoogle Scholar
  15. 15.
    Christen T, Trompet S, Noordam R et al (2018) Mendelian randomization analysis of cholesteryl ester transfer protein and subclinical atherosclerosis: A population-based study. J Clin Lipidol 12(1):137–144.e1CrossRefGoogle Scholar
  16. 16.
    Lagrost L (1999) relationship of cholesteryl ester transfer protein to atherosclerosis. In: Plasma Lipids and Their Role in Disease p. 217‑31. (Advances Vascular Biology; vol. 5)Google Scholar
  17. 17.
    Chapman MJ, Le Goff W, Guerin M, Kontush A (2010) Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors. Eur Heart J 31(2):149–164CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology, Diabetes and Metabolic DisordersDijon University HospitalDijonFrance
  2. 2.INSERM Unit, LNC-UMR 1231University of BurgundyDijonFrance
  3. 3.Angiology DepartmentDijon University HospitalDijonFrance

Personalised recommendations