Download PDF
Horm Metab Res 1999; 31(12): 665-671
DOI: 10.1055/s-2007-978818
Originals Clinical

© Georg Thieme Verlag Stuttgart · New York

High Dose Supplementation of RRR-α-Tocopherol Decreases Cellular Hemostasis but Accelerates Plasmatic Coagulation in Type 2 Diabetes Mellitus

P. Ferber, K. Moll, T. Koschinsky, P. Rösen, F. Susanto, B. Schwippert, D. Tschöpe
  • German Diabetes Research Institute at the Heinrich-Heine University, Düsseldorf, Germany
Parts of this work have been released in abstract form on the occasions of the 1998 Annual Meeting of the German Diabetes Society, the 1999 Annual Meeting of the German Society for Internal Medicine and the 1999 Annual Meeting of the American Diabetes Association.
Further Information

Publication History

1999

1999

Publication Date:
20 April 2007 (online)

Also available at
  PDF Download  Permissions and Reprints

Abstract

Background: Diabetes mellitus is associated with increased generation of free oxygen radicals and depleted scavenging potential (oxidative stress), leading to increased LDL oxidation and platelet hyperreactivity, the major components of atherothrombotic vascular lesions. A main goal of antioxidant therapy is to protect the LDL particle from atherogenic oxidation and to reduce the activated cellular hemostasis. Methods: We evaluated the influence of a high dose supplementation with 800 IU of the natural antioxidant RRR-α-tocopherol (vitamin E) per day for six months on serum levels, vitamin E load of LDL particles (HPLC), lag phase of LDL oxidation (Esterbauer's assay), platelet adhesion molecules, leukocyte-platelet coaggregation (flow cytometry, D-III protocol) and coagulation (INR/PTT) in a group of 36 patients with type 2 diabetes (f/m 22/14; age 58 ± 8.0; HbA1 at baseline 10.25 ± 1.7). Results: Average vitamin E levels increased 2.65-fold accompanied by a 1.83-fold increase of LDL-associated vitamin E and a 12.3 min prolongation of the lag-phase of LDL oxidation (p < 0.001 for all parameters at six months). Platelet expression of PECAM-1 (CD31) (-30.2% positive cells, p < 0.001; antigen density -25%, p < 0.001), ICAM-2 (CD102) (-2.9% positive cells, p < 0.01; antigen density -10.6%, p < 0.001) and fibrinogen (-1.6% positive cells, p < 0.001; antigen density -16.1%, p < 0.001) decreased. Concomitantly, platelet-leukocyte-coaggregation increased by 44% (p < 0.001), correlating to an INR reduction of 10.4% (1.06 ± 0.09 to 0.95 ± 0.09, p < 0.001, r = -0.34). The PTT remained constant. Conclusion: The antioxidant protection from the increased vitamin E was accompanied by a decreased expression of constitutive and function-dependent platelet adhesion molecules. However, increases in platelet-leukocyte coaggregates and a shortened INR time suggest extrinsic coagulation activation, possibly by induction of a leukocyte tissue factor dependent mechanism. High dose supplements of α-tocopherol may override the available redox balance in well controlled type 2 diabetes. However, intrinsic effects of α-tocopherol must be discussed.

Key words

Platelet Activation - Oxidative Stress - Antioxidants - Atherosclerosis