Yasuda Satoshi, Miyazaki Shunichi, Kanda Munetake, Goto Yoichi, Suzuki Masaaki, Harano Yutaka, Nonogi Hiroshi
Division of Cardiology, Department of Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Eur Heart J. 2006 May;27(10):1159-65. doi: 10.1093/eurheartj/ehi876. Epub 2006 Apr 20.
Vascular endothelium is a major organ involved in hyperglycaemia and is affected by plasma asymmetric dimethylarginine (ADMA). ADMA is an endogenous, competitive inhibitor of nitric oxide synthase and is induced by inflammatory cytokines of tumour necrosis factor (TNF)-alpha in vitro. We hypothesized that a tight glycaemic control may restore endothelial function in patients with type-2 diabetes mellitus (DM), in association with modulation of TNF-alpha and/or reduction of ADMA level.
In 24 patients with type-2 DM, the flow-mediated, endothelium-dependent dilation (FMD: %) of brachial arteries during reactive hyperaemia was determined by a high-resolution ultrasound method. Blood samples for glucose, cholesterol, TNF-alpha, and ADMA analyses were also collected from these patients after fasting. No significant glycaemic or FMD changes were observed in 10 patients receiving the conventional therapy. In 14 patients who were hospitalized and intensively treated, there was a significant decrease in glucose level after the treatment [from 190+/-55 to 117+/-21 (mean+/-SD) mg/dL, P<0.01]. After the intensive control of glucose level, FMD increased significantly (from 2.5+/-0.9 to 7.2+/-3.0%), accompanied by a significant (P<0.01) decrease in TNF-alpha (from 29+/-16 to 11+/-9 pg/dL) and ADMA (from 4.8+/-1.5 to 3.5+/-1.1 microM/L) levels. The changes in FMD after treatment correlated inversely with those in TNF-alpha (R=-0.711, P<0.01) and ADMA (R=-0.717, P<0.01) levels.
The intensive correction of hyperglycaemia is associated with the improvement of endothelial function, which is coupled with the decrease in the levels of reduction of plasma TNF-alpha and ADMA in patients with type-2 DM. A strict glycaemic control may exert anti-cytokine and anti-atherogenic effects and may therefore be pathophysiologically important.
血管内皮是参与高血糖的主要器官，且受血浆不对称二甲基精氨酸（ADMA）影响。ADMA是一氧化氮合酶的内源性竞争性抑制剂，在体外可被肿瘤坏死因子（TNF）-α等炎性细胞因子诱导产生。我们推测，严格的血糖控制可能通过调节TNF-α和/或降低ADMA水平来恢复2型糖尿病（DM）患者的内皮功能。
对24例2型DM患者，采用高分辨率超声法测定反应性充血期间肱动脉的血流介导的内皮依赖性舒张功能（FMD：%）。这些患者在空腹状态下还采集了用于血糖、胆固醇、TNF-α和ADMA分析的血样。10例接受常规治疗的患者未观察到明显的血糖或FMD变化。14例住院并接受强化治疗的患者，治疗后血糖水平显著降低[从190±55降至117±21（均值±标准差）mg/dL，P<0.01]。血糖水平强化控制后，FMD显著增加（从2.5±0.9升至7.2±3.0%），同时TNF-α（从29±16降至11±9 pg/dL）和ADMA（从4.8±1.5降至3.5±1.1 μmol/L）水平显著降低（P<0.01）。治疗后FMD的变化与TNF-α（R=-0.711，P<0.01）和ADMA（R=-0.717，P<0.01）水平的变化呈负相关。
强化纠正高血糖与内皮功能改善相关，同时2型DM患者血浆TNF-α和ADMA水平降低。严格的血糖控制可能发挥抗细胞因子和抗动脉粥样硬化作用，因此在病理生理学上可能具有重要意义。
