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Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients

  • M. Mashavi
    Affiliations
    Department of Medicine, Wolfson Medical Center, Tel Aviv, Israel

    Department of Diabetes, Wolfson Medical Center, Tel Aviv, Israel

    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • R. Hanah
    Affiliations
    Department of Medicine, Wolfson Medical Center, Tel Aviv, Israel
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  • M. Boaz
    Affiliations
    Department of Epidemiology and Statistics, Wolfson Medical Center, Tel Aviv, Israel
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  • D. Gavish
    Affiliations
    Department of Medicine, Wolfson Medical Center, Tel Aviv, Israel

    Bruner Institute for Cardiovascular Research, Tel Aviv University, Tel Aviv, Israel

    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Z. Matas
    Affiliations
    Department of Biochemistry, Wolfson Medical Center, Tel Aviv, Israel
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  • A. Fux
    Affiliations
    Department of Biochemistry, Wolfson Medical Center, Tel Aviv, Israel
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  • M. Shargorodsky
    Correspondence
    Corresponding author at: Wolfson Medical Center, POB 5, Holon 58100, Israel. Tel.: +972 3 5028614; fax: +972 3 5032693.
    Affiliations
    Department of Diabetes, Wolfson Medical Center, Tel Aviv, Israel

    Department of Endocrinology, Wolfson Medical Center, Tel Aviv, Israel

    Bruner Institute for Cardiovascular Research, Tel Aviv University, Tel Aviv, Israel

    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author

      Abstract

      Metformin may affect the risk of atherothrombotic disease. However, metformin increases levels of homocysteine (Hcy), considered an independent risk factor for atherosclerosis. We evaluate whether homocysteine-lowering has a beneficial effect on arterial elasticity and metabolic parameters in metformin-treated diabetic patients. In double-blind, placebo-controlled study, 60 diabetic patients treated with high dose of metformin were randomly assigned to receive daily oral supplementation with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10 mg) (group 1) or placebo (group 2). Lipid profile, HbA1C, insulin, C-peptide, hs-CRP, vitamin B12, folic acid, homocysteine, endothelin, homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, MN). The two groups were similar at baseline in terms of hemodynamic and arterial elasticity parameters. After a 4-month small artery elasticity index (SAEI) was significantly greater in patients who received Hcy-lowering agents than in the placebo group: 4.3 ± 2.04 ml/mm Hg × 100 versus 3.2 ± 1.1 ml/mm Hg × 100, p = 0.01. Post-treatment vitamin B12 and folic acid levels were greater in group 1 versus group 2: 738.1 ± 279.9 pg/ml versus 566.1 ± 167.4 pg/ml, p = 0.007 and 14.9 ± 4.8 ng/ml versus 8.3 ± 2.9 ng/ml, p < 0.0001, respectively. Hcy level decreased significantly in the treatment group from 10.0 ± 4.4 to 7.6 ± 2.5 μmol/l, p = 0.002 and did not change in placebo group (p = 0.9). Hcy-lowering therapy improved small arterial elasticity in diabetic patients treated with high dose of metformin. The improvement was associated with a decrease in Hcy as well as an increase in folic acid and vitamin B12. These findings suggest that Hcy-lowering may have beneficial vascular effect in metformin-treated diabetic patients.

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