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.
Keywords
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Article info
Publication history
Published online: January 21, 2008
Accepted:
November 28,
2007
Received in revised form:
October 25,
2007
Received:
July 23,
2007
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
