Vaccaro O, Perna A F, Mancini F P, Iovine C, Cuomo V, Sacco M, Tufano A, Rivellese A A, Ingrosso D, Riccardi G
Department of Clinical and Experimental Medicine, School of Medicine, Federico II University, S. Pansini 5, 80131 Napoli, Italy.
Nutr Metab Cardiovasc Dis. 2000 Dec;10(6):297-304.
Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally.
We studied sixty-six consecutive patients with type 1 diabetes mellitus of > 10 years duration and normal serum creatinine (< 115 mumol/L, 1.3 mg/dL), and free from clinically detectable cardiovascular diseases. Forty-four non-diabetic controls were also studied. Plasma concentrations of homocysteine, folate and vitamin B12 were investigated together with the C677T mutation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal diabetic complications were evaluated as albumin/creatinine ratio on early-morning, urine spot collection and fundus photographs.
Fasting plasma homocysteine levels were very similar in patients and controls. Patients with microalbuminuria or proliferative retinopathy had significantly higher values than those without: 9.4 +/- 3.1 vs 7.4 +/- 2.8 mumol/L, p < 0.02 and 9.5 +/- 2.6 vs 7.3 +/- 3.0 mumol/L, p < 0.05. This difference was not attributable to confounders, such as age, sex and smoking, nor to dissimilar plasma folate and vitamin B12 concentrations. In contrast, homozygosity for the C677T mutation in the MTHFR gene--the commonest genetic defect linked to moderately increased plasma homocysteine--was significantly more frequent in patients with microalbuminuria and/or proliferative retinopathy (50% vs 13%, p < 0.004), odds ratio 6.7 (95% CI 1.7-27.6).
Type 1 diabetes as such is not associated with increased plasma homocysteine levels, though patients with microalbuminuria and/or proliferative retinopathy display significantly higher values than those without. This difference is not attributable to obvious confounders, nor to differences in vitamin status, and may be partly mediated by genetic factors. Plasma homocysteine, together with other diabetes-related noxae, may thus be in a position to contribute to the development of nephropathy and the progression of retinopathy.
同型半胱氨酸参与血管损伤与修复的复杂动态系统，因此可能促使糖尿病微血管病变的发生。这一仍存在争议的问题具有重要的科学及临床意义，因为高同型半胱氨酸血症可通过营养方式得到纠正。
1）评估空腹血浆同型半胱氨酸、1型糖尿病及其微血管并发症之间的关联；2）通过研究与糖尿病微血管病变相关的血浆同型半胱氨酸的主要决定因素，阐明这种关联的基础。
我们研究了66例病程超过10年且血清肌酐正常（<115μmol/L，1.3mg/dL）、无临床可检测到的心血管疾病的1型糖尿病患者。还研究了44名非糖尿病对照者。检测了血浆同型半胱氨酸、叶酸和维生素B12的浓度，以及编码亚甲基四氢叶酸还原酶（MTHFR）的基因中的C677T突变，MTHFR是同型半胱氨酸代谢中的关键酶。通过清晨尿点样收集的白蛋白/肌酐比值和眼底照片评估糖尿病肾病和视网膜病变。
患者和对照者的空腹血浆同型半胱氨酸水平非常相似。微量白蛋白尿或增殖性视网膜病变患者的值显著高于无这些病变的患者：分别为9.4±3.1 vs 7.4±2.8μmol/L，p<0.02；以及9.5±2.6 vs 7.3±3.0μmol/L，p<0.05。这种差异并非归因于年龄、性别和吸烟等混杂因素以及血浆叶酸和维生素B12浓度的差异。相比之下，MTHFR基因C677T突变的纯合子——与血浆同型半胱氨酸适度升高相关的最常见遗传缺陷——在微量白蛋白尿和/或增殖性视网膜病变患者中显著更常见（50% vs 13%，p<0.004），比值比为6.7（95%CI 1.7 - 27.6）。
1型糖尿病本身与血浆同型半胱氨酸水平升高无关，尽管微量白蛋白尿和/或增殖性视网膜病变患者的值显著高于无这些病变的患者。这种差异并非归因于明显的混杂因素，也不是维生素状态的差异，可能部分由遗传因素介导。因此，血浆同型半胱氨酸与其他糖尿病相关的有害物质可能共同促使肾病的发生和视网膜病变的进展。
