Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study
Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study
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DOI：
10.1186/1475-2840-11-124
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发表时间：
2012-10-10
影响因子：
9.3
通讯作者：
Smits, Paul
中科院分区：
文献类型：
--
作者：
Engbersen, Richard;Riksen, Niels P.;Smits, Paul
背景：在1型糖尿病（T1DM）患者中，心血管事件更为常见，心肌梗死后的结果比非糖尿病患者更差。缺血或药物预处理是减少缺血再灌注（IR）损伤的有力干预措施。然而，动物研究表明，T1DM的存在会限制这些保护作用。因此，我们旨在研究缺血预处理对T1DM患者的保护作用，并探讨血浆胰岛素和葡萄糖在这一作用中的作用。方法：采用（99m） technology -annexin A5显像检测ir损伤。单侧前臂缺血运动诱导ir损伤。再灌注时给予tc -膜联蛋白A5，再灌注后4小时，用实验组和对照组大鼠大鱼际肌肉放射性差异百分比表示ir损伤。15例T1DM患者与21例非糖尿病对照。患者进行了两次研究，有或没有缺血预处理（10分钟前臂缺血再灌注）。研究对象为正常血糖高胰岛素血症患者（n = 8）和正常血糖高胰岛素血症患者（n = 7）。对照组分别接受（n = 8）或不接受（n = 13）缺血预处理。结果：糖尿病患者对ir损伤的易损性低于非糖尿病健康对照组（12.8 +/- 2.4和11.0 +/- 5.1%，对照组为27.5 +/- 4.5%;p < 0.05）。然而，在高血糖患者中，缺血预处理减少ir损伤的效果较低，甚至完全消失。结论：在我们的实验模型中，T1DM患者比健康对照组更能耐受前臂IR。然而，急性高血糖降低了缺血预处理限制ir损伤的功效。
Background: In patients with type 1 diabetes mellitus (T1DM), cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR)-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects. Therefore, we aimed to study the protective effect of ischemic preconditioning in patients with T1DM, and to explore the role of plasma insulin and glucose on this effect.Methods: (99m)Technetium-annexin A5 scintigraphy was used to detect IR-injury. IR-injury was induced by unilateral forearm ischemic exercise. At reperfusion, Tc-annexin A5 was administered, and IR-injury was expressed as the percentage difference in radioactivity in the thenar muscle between the experimental and control arm 4 hours after reperfusion. 15 patients with T1DM were compared to 21 nondiabetic controls. The patients were studied twice, with or without ischemic preconditioning (10 minutes of forearm ischemia and reperfusion). Patients were studied in either normoglycemic hyperinsulinemic conditions (n = 8) or during hyperglycemic normoinsulinemia (n = 7). The controls were studied once either with (n = 8) or without (n = 13) ischemic preconditioning.Results: Patients with diabetes were less vulnerable to IR-injury than nondiabetic healthy controls (12.8 +/- 2.4 and 11.0 +/- 5.1% versus 27.5 +/- 4.5% in controls; p < 0.05). The efficacy of ischemic preconditioning to reduce IR-injury, however, was lower in the patients and was even completely abolished during hyperglycemia.Conclusions: Patients with T1DM are more tolerant to forearm IR than healthy controls in our experimental model. The efficacy of ischemic preconditioning to limit IR-injury, however, is reduced by acute hyperglycemia.