Hogikyan R V, Galecki A T, Pitt B, Halter J B, Greene D A, Supiano M A
Department of Internal Medicine, University of Michigan, USA.
J Clin Endocrinol Metab. 1998 Jun;83(6):1946-52. doi: 10.1210/jcem.83.6.4907.
In subjects with type 2 diabetes in whom an impaired response to an endothelial-dependent vasodilator has been characterized, the populations have also been at least moderately obese. Obesity has been characterized as an independent predictor of endothelial dysfunction in nondiabetic subjects. We hypothesized that in normotensive subjects with type 2 diabetes compared with age-matched control subjects, 1) endothelium-dependent vasodilation, as demonstrated by the forearm blood flow (FABF) response to intraarterial acetylcholine, would be decreased; 2) endothelium-independent vasodilation, as demonstrated by the FABF response to intraarterial nitroprusside, would be similar; 3) the degree of insulin resistance, as measured by the insulin sensitivity index (SI), would predict greater impairment in the FABF response to acetylcholine; and 4) these relationships would be independent of obesity. We measured FABF by venous occlusion plethysmography during brachial arterial infusions of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator nitroprusside in 20 control and 17 subjects with type 2 diabetes. We measured SI using the frequently sampled i.v. glucose tolerance test. Among the diabetic relative to the control subjects we identified a decrease in the acetylcholine-mediated percent increase in FABF (P = 0.02). Using the absolute FABF response to acetylcholine and including adjustments for body mass index and other covariates, the overall group difference remained and was noted to be greatest in those subjects who had lower baseline FABFs. In contrast, no significant difference in the nitroprusside-mediated increase in the percent change FABF was identified between groups (P = 0.30). Finally, the degree of insulin resistance, as measured by SI, did not independently predict greater impairment of the FABF response to acetylcholine. This study is the first to identify specific endothelial cell dysfunction that remains significant after adjustment for obesity in a population of normotensive subjects with type 2 diabetes.
在已被证实存在内皮依赖性血管舒张反应受损的2型糖尿病患者中，这些人群也至少为中度肥胖。肥胖已被视为非糖尿病患者内皮功能障碍的独立预测因素。我们推测，与年龄匹配的对照受试者相比，在血压正常的2型糖尿病患者中，1）通过前臂血流量（FABF）对动脉内乙酰胆碱的反应所证明的内皮依赖性血管舒张会降低；2）通过FABF对动脉内硝普钠的反应所证明的非内皮依赖性血管舒张会相似；3）通过胰岛素敏感性指数（SI）测量的胰岛素抵抗程度将预示对乙酰胆碱的FABF反应有更大损害；4）这些关系将独立于肥胖。我们在20名对照受试者和17名2型糖尿病受试者中，通过静脉闭塞体积描记法在肱动脉输注内皮依赖性血管舒张剂乙酰胆碱和非内皮依赖性血管舒张剂硝普钠期间测量FABF。我们使用频繁采样的静脉葡萄糖耐量试验测量SI。与对照受试者相比，糖尿病患者中乙酰胆碱介导的FABF百分比增加有所降低（P = 0.02）。使用对乙酰胆碱的绝对FABF反应并纳入体重指数和其他协变量的调整后，总体组间差异仍然存在，并且在基线FABF较低的受试者中最为明显。相比之下，两组之间硝普钠介导的FABF百分比变化增加没有显著差异（P = 0.30）。最后，通过SI测量的胰岛素抵抗程度并不能独立预测对乙酰胆碱的FABF反应有更大损害。本研究首次在血压正常的2型糖尿病患者人群中发现，在对肥胖进行调整后，特定的内皮细胞功能障碍仍然显著。
