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1.
J Neurooncol ; 82(1): 113-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16972187
2.
Neth J Med ; 62(7): 246-53, 2004.
Article in English | MEDLINE | ID: mdl-15554600

ABSTRACT

BACKGROUND: Mild hyperhomocysteinaemia is a cardiovascular risk factor in patients with type 2 diabetes mellitus. Homocysteine may exert its detrimental effects through induction of endothelial dysfunction and/or chronic inflammation. In this study, we examined the effects of homocysteine-lowering therapy with folic acid on biochemical markers of endothelial dysfunction and low-grade inflammation in patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia (> or = 14 micromol/l). METHODS: In a randomised, double-blind, controlled trial, patients were treated with folic acid 5 mg or placebo for six months. At 0 and 6 months, albuminuria, von Willebrand factor, soluble cellular adhesion molecules, C-reactive protein, interleukin-6 and tumour necrosis factor-alpha were determined. RESULTS: Forty-one patients completed the study (folic acid 23, placebo 18). Baseline hyperhomocysteinaemia (median 17 micromol/l, range 14 to 30 micromol/l) was reduced by 29% in the folic-acid-treated group, and remained unchanged in patients receiving placebo. On average, folic acid treatment did not significantly affect any of the endothelial (e.g. von Willebrand factor: difference folic acid minus placebo +1%, confidence interval -3 to +16%) or inflammation (e.g. C-reactive protein: difference folic acid minus placebo +13%, confidence interval -42 to +52%) markers studied. Multiple regression analyses without and with adjustment for baseline differences in cardiovascular disease and ethnicity confirmed these results. An apparent beneficial effect of folic acid on albuminuria in crude analysis was attenuated by multiple adjustment (difference folic acid minus placebo -35%, confidence interval -178 to +32%, p=0.08, adjusted 0.26). CONCLUSION: The data indicate that, in this group of patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia, lowering homocysteine with folic acid for six months does not improve biochemical markers of endothelial dysfunction or low-grade inflammation.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Endothelium/drug effects , Folic Acid/pharmacology , Homocysteine/drug effects , Hyperhomocysteinemia/drug therapy , Inflammation/drug therapy , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/immunology , Endothelium/physiopathology , Female , Folic Acid/therapeutic use , Humans , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/immunology , Inflammation/immunology , Male , Middle Aged , Risk Factors
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