Original article
Influence of vitamin E supplementation on endothelial complications in type 2 diabetes mellitus patients who underwent coronary artery bypass graft

https://doi.org/10.1016/j.jdiacomp.2007.10.006Get rights and content

Abstract

Background

Diabetes mellitus (DM) is associated with increased risk for complications following coronary artery bypass graft (CABG) surgery, in which tissue damage involves leukocyte–endothelial interactions mediated by endothelin-1 (ET-1) and adhesion molecules (AMs).

Aim

This study compared lipids and their peroxidation product, malondialdehyde (MDA), high-sensitivity C-reactive protein (hsCRP), ET-1, platelet-selectin (P-selectin), intercellular AM-1 (ICAM-1), and vascular cell AM-1 (VCAM-1) between healthy controls and type 2 DM subjects who did not receive CABG surgery as well as those who did. Vitamin E as an adjunctive therapy in subjects who underwent CABG was evaluated.

Methods

ELISA was used to measure hsCRP, ET-1, and AMs. For all subjects, glycosylated hemoglobin (HbA1c) and lipid profile were estimated.

Results

Percentage of HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in healthy controls. Vitamin E supplementation for 3 successive months significantly lowered MDA, hsCRP, ET-1, ICAM-1, and VCAM-1 levels by 64%, 47%, 12%, 74%, and 25%, respectively. However, high-density lipoprotein cholesterol (HDL-C) and vitamin E serum levels were increased by 65% and 90.55%, respectively (P≤.05). Vitamin E cosupplementations correlated restored ET-1, P-selectin, and ICAM-1 levels, which have been functionally damaged by decreased HDL-C, hypercholesterolemia, and hypertriacylglycerolemia, respectively.

Conclusion

This study indicates that increased levels of the proinflammatory markers and AMs occur in type 2 DM. Vitamin E administration appears beneficial in lowering proinflammatory markers and their downstream effectors that played an important role in diabetic complications following CABG.

Introduction

Cardiovascular (CV) morbidity is a major burden in patients with type 2 diabetes mellitus (DM) (Fritz, Wandell, Aberg, & Engfeldt, 2006), with endothelial dysfunction as an early sign of diabetic vascular disease (Stenina, 2005), which is related to the presence of a vascular low-grade inflammation. Also, type 2 DM is associated with increased risk for complications following coronary artery bypass grafting (CABG) surgery, by inducing inflammatory vascular dysfunction (Ergul et al., 2005). Alteration in endothelin-1 (ET-1) secretion of the endothelium is the key event in the initiation of arteriosclerosis (Tostes & Muscara, 2005), via activation of leukocyte adhesion (Insel et al., 2004), which is linked to the presence of a vascular inflammation. Cellular adhesion molecules (CAMs), namely, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are poorly expressed by the resting endothelium but are up-regulated during inflammatory atherogenesis and may be an index of endothelial activation (Meydani, 2003). Postprandial rises in plasma glucose can trigger endothelial damage through increased oxidative stress and atherogenic CAM expression (Home, 2005), which increases antioxidant requirements (Davi, Falco, & Patrono, 2005). The use of micronutrients with antioxidant properties as vitamin E may play an important role in the reduction of type-2-DM-induced CV morbidity and mortality (Antoniades et al., 2003).

The aim of this study was to evaluate the levels of lipids, malondialdehyde (MDA), high-sensitivity C-reactive protein (hsCRP), ET-1, platelet-selectin (P-selectin), ICAM-1, and VCAM-1 among healthy controls and type 2 DM subjects whom did not undergo CABG surgery as well those who did. Furthermore, the effect of vitamin E supplementation for 3 successive months was evaluated in the CABG group to assess its role in inflammatory endothelial dysfunction.

Section snippets

Subjects

The studied groups included 42 males, of which 12 served as healthy controls. None of the controls took any medication or dietary supplements including vitamin(s) and/or antioxidant(s) during the study. Thirty males were selected from patients admitting to Ain Shams University Specialized Hospitals Cardiology department. After protocol approval, the study was conducted in the period from September 2004 to May 2005. Fifteen type 2 DM subjects whom did not undergo CABG and 15 who did (not less

Results

The baseline characteristics of the studied participants are presented in Table 1. As indicated in Table 2, the median values of MDA, hsCRP, ET-1, ICAM-1, and VCAM-1 concentrations were significantly higher in the diabetic subgroups in comparison to those obtained in the control group (P<.05). Type 2 DM patients presented lower vitamin E levels in comparison to controls (P≤.01). On the other hand, no significant differences among the diabetic subgroups were observed in all parameters. The

Discussion

When raised TAG coexists with an atherogenic cholesterol profile, the overall risk is enhanced (Waller, Renwick, & Hillier, 2001). Impairment of vascular endothelial function is an initial step in the development of inflammatory atherosclerosis (Vitale et al., 2001). The higher incidence of atherosclerotic vascular disease in patients with type 2 DM may also be related to the atherogenic properties of ET-1 (Insel et al., 2004). Activated platelets play an important role in coagulation and

Conclusions

In conclusion, our study shows that some surrogate markers of CV inflammation are elevated in diabetic patients. Taken together, these data support the opinion that diabetic patients present a high risk for CVD and need early aggressive intervention. Increased oxidative stress and inflammation in type 2 DM after CABG could be partly overcome by vitamin E administration. Improvement in endothelial function observed in this study appears to be related to an improvement in the oxidative

References (28)

  • E. Ercan et al.

    Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris

    Thrombosis Journal

    (2004)
  • A. Ergul et al.

    Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: Role of endothelin-1

    Journal of Pharmacology and Experimental Therapeutics

    (2005)
  • W.T. Friedewald et al.

    Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of preparative ultracentrifuge

    Clinical Chemistry

    (1972)
  • M.T. Gladwin et al.

    Divergent nitric oxide bioavailability in men and women with sickle cell disease

    Circulation

    (2003)
  • Cited by (18)

    • Effect of Salvia miltiorrhiza on Antioxidant Enzymes in Diabetic Patients

      2013, Diabetes: Oxidative Stress and Dietary Antioxidants
    • The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion

      2012, Pharmacology and Therapeutics
      Citation Excerpt :

      The second compound supplemented as an antioxidant during CABG is α-tocopherol, or vitamin E, which can scavenge peroxyl radicals in biological lipid membranes (Sies & Stahl, 1995; Brigelius-Flohe & Traber, 1999). Similar to N-acetylcysteine, α-tocopherol appears capable of reducing markers of oxidative stress, but the overall clinical benefit appears to be limited (Yau et al., 1994; Westhuyzen et al., 1997; Hamdy et al., 2009). Interestingly, the intracoronary administration of α-tocopherol was found to improve post-reperfusion troponin I and CK-MB profiles relative to control (Canbaz et al., 2003).

    View all citing articles on Scopus

    The authors state that there are no conflicts of interest.

    View full text