Effect of acute ketosis on the endothelial function of type 1 diabetic patients -: The role of nitric oxide
Effect of acute ketosis on the endothelial function of type 1 diabetic patients -: The role of nitric oxide
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DOI：
10.2337/diabetes.48.2.391
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发表时间：
1999-02-01
期刊：
影响因子：
7.7
通讯作者：
Del Prato, S
中科院分区：
文献类型：
--
作者：
Avogaro, A;Calò, L;Del Prato, S
在 1 型糖尿病患者中，代谢控制的急剧丧失与血流量增加有关，这被认为有利于长期并发症的发生。不适当的血管舒张机制已被部分了解，但可以推测内皮源性一氧化氮 (NO) 产生的作用。我们在 1 型糖尿病患者中评估了代谢控制急性丧失及其恢复对 13 名 1 型糖尿病患者前臂内皮功能的影响，这些患者在两个不同场合的轻度酮症条件下进行了研究。在研究 I 中，在基础测定后，通过胰岛素输注获得了代谢情况的快速改善。在研究 2 中，7 名 1 型糖尿病患者接受了相同的实验程序，只是空腹血糖自始至终保持恒定。在静脉注射胰岛素之前和之后测定亚硝酸盐/硝酸盐（NO2- + NO3-）的基础血浆静脉浓度。分别通过动脉内输注N-G-单甲基-L-精氨酸（L-NMMA）和硝普钠（SNP）来评估肱动脉的内皮依赖性和非依赖性血管舒张。在基线条件下和高胰岛素正常血糖钳夹期间，对 13 名对照受试者测定了相同的参数。 1 型糖尿病患者的基线前臂血流量（4.89 +/- 0.86 对比 3.65 +/- 0.59 mi（100 mi 组织）(-1) min(-1)）和 NO、+ NO 浓度（30 +/- 8 对比 24 +/- 3 μmol/l）高于对照组（P < 0.05）。与酮症条件下的患者相比，胰岛素输注与较低的前臂血流量和血浆（NO2- + NO3-）浓度相关（P < 0.05），无论当时的血糖水平如何。 1型糖尿病患者在正常血糖和高血糖高胰岛素血症期间（输注臂与对照组的比例分别为-11 +/- 5和-10 +/- 4%）对L-NMR IA的反应显着低于基线时（-18 +/- 6%，P < 0.05）和高胰岛素血症期间（-32 +/- 11%，P < 0.01）的对照受试者。我们得出的结论是，代谢控制的急性丧失与内皮功能的功能紊乱有关，其特征是酮症期间充血和NO释放增加，以及静脉注射胰岛素恢复代谢控制期间NO介导的血管舒张反应减弱。这种功能改变不太可能用高血糖本身来解释。
In type 1 diabetic patients, acute loss of metabolic control is associated with increased blood flow, which is believed to favor the development of long-term complications. The mechanisms for inappropriate vasodilation are partially understood, but a role of endothelium-derived nitric oxide (NO) production can be postulated. We assessed, in type 1 diabetic patients, the effect of the acute loss of metabolic control and its restoration on forearm endothelial function in 13 type 1 diabetic patients who were studied under conditions of mild ketosis on two different occasions. In study I, after basal determination, a rapid amelioration of the metabolic picture was obtained by insulin infusion. In study 2, seven type 1 diabetic patients underwent the same experimental procedure, except that fasting plasma glucose was maintained constant throughout. Basal plasma venous concentrations of nitrites/nitrates (NO2- + NO3-) were determined both before and after intravenous insulin infusion. Endothelium-dependent and -independent vasodilation of the brachial artery was assessed by an intra-arterial infusion of N-G-monomethyl-L-arginine (L-NMMA) and sodium nitroprusside (SNP), respectively. The same parameters were determined in 13 control subjects at baseline conditions and during a hyperinsulinemic-euglycemic glucose clamp. Baseline forearm blood flow (4.89 +/- 0.86 vs. 3.65 +/- 0.59 mi (100 mi tissue)(-1) min(-1)) and NO, + NO, concentration (30 +/- 8 vs. 24 +/- 3 mu mol/l) were higher in type 1 diabetic patients than in control subjects (P < 0.05). Insulin infusion was associated with lower forearm blood flow and plasma (NO2- + NO3-) concentration (P < 0.05), irrespective of the prevailing glucose levels, as compared with patients under ketotic conditions. The responses to L-NMR IA were significantly lower in type 1 diabetic patients during euglycemia and hyperglycemic hyperinsulinemia (-11 +/- 5 and -10 +/- 4%, respectively, of the ratio of the infused arm to the control arm) than in control subjects at baseline (-18 +/- 6%, P < 0.05) and during hyperinsulinemia (-32 +/- 11%, P < 0.01). We conclude that the acute loss of metabolic control is associated with a functional disturbance of the endothelial function characterized by hyperemia and increased NO release during ketosis and blunted NO-mediated vasodilatory response during restoration of metabolic control by intravenous insulin. This functional alteration is unlikely to be explained by hyperglycemia itself.