Spoelstra-de Man A M E, Brouwer C B, Terheggen F, Bollen J M, Stehouwer C D A, Smulders Y M
Department of Internal Medicine, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
Neth J Med. 2004 Jul-Aug;62(7):246-53.
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).
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.
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).
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.
轻度高同型半胱氨酸血症是2型糖尿病患者的心血管危险因素。同型半胱氨酸可能通过诱导内皮功能障碍和/或慢性炎症发挥其有害作用。在本研究中，我们研究了用叶酸降低同型半胱氨酸治疗对2型糖尿病合并轻度高同型半胱氨酸血症（≥14微摩尔/升）患者内皮功能障碍和低度炎症生化标志物的影响。
在一项随机、双盲、对照试验中，患者接受5毫克叶酸或安慰剂治疗6个月。在0个月和6个月时，测定蛋白尿（白蛋白尿）、血管性血友病因子、可溶性细胞黏附分子、C反应蛋白、白细胞介素-6和肿瘤坏死因子-α。
41例患者完成了研究（叶酸组23例，安慰剂组18例）。叶酸治疗组的基线高同型半胱氨酸血症（中位数17微摩尔/升，范围14至30微摩尔/升）降低了29%，而接受安慰剂的患者则保持不变。平均而言，叶酸治疗对所研究的任何内皮标志物（如血管性血友病因子：叶酸减去安慰剂的差值为+1%，置信区间为-3至+16%）或炎症标志物（如C反应蛋白：叶酸减去安慰剂的差值为+13%，置信区间为-42至+52%）均无显著影响。未对心血管疾病和种族的基线差异进行调整以及进行调整后的多元回归分析均证实了这些结果。在粗分析中，叶酸对蛋白尿的明显有益作用在多重调整后减弱（叶酸减去安慰剂的差值为-35%，置信区间为-178至+32%，p=0.08，调整后为0.26）。
数据表明，在这组2型糖尿病合并轻度高同型半胱氨酸血症患者中，用叶酸降低同型半胱氨酸6个月并不能改善内皮功能障碍或低度炎症的生化标志物。
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