终末期肾衰竭糖尿病患者血小板钙稳态紊乱。这与心血管死亡率增加有关联吗？

Deranged platelet calcium homeostasis in diabetic patients with end-stage renal failure. A possible link to increased cardiovascular mortality?

作者信息

Vicari A M, Taglietti M V, Pellegatta F, Spotti D, Melandri M, Galli L, Ronchi P, Folli F

机构信息

Department of Medicine, IRCCS H. San Raffaele, Milano, Italy.

出版信息

Diabetes Care. 1996 Oct;19(10):1062-6. doi: 10.2337/diacare.19.10.1062.

DOI:10.2337/diacare.19.10.1062

PMID:8886550

Abstract

OBJECTIVE

Platelet hyperfunction is a typical feature of the prothrombotic state that frequently complicates the natural history of diabetes. In uremia, a bleeding diathesis is present, which principally involves the primary phase of hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent coexistence of two opposite alterations of hemostasis takes place. In patients with uremia, an increased incidence of cardiovascular events and related mortality is observed. This phenomenon is greatly amplified in uremia of diabetic origin. Calcium homeostasis is a critical aspect of platelet function, which has recently become available in human diseases. The aim of this study was to evaluate calcium homeostasis in platelets from patients with uremia of diabetic and nondiabetic origin.

RESEARCH DESIGN AND METHODS

We evaluated, by means of Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets from 18 patients with uremia of diabetic origin, 12 patients with uremia of nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin.

RESULTS

Platelets from uremic patients with diabetes had higher resting [Ca2+]i than both control subjects (P = 0.01) and uremic patients without diabetes (P = 0.001). Similarly, after stimulation with thrombin, the absolute increase of [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes compared with both control subjects and uremic patients without diabetes. The relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from uremic patients after weak or intermediate strength thrombin. No correlation were present between [Ca2+]i values and other clinical and laboratory variables potentially associated with platelet hyperfunction.

CONCLUSIONS

Diabetes and uremia in combination further deteriorate the abnormal platelet calcium homeostasis observed in uremia.

摘要

目的

血小板功能亢进是血栓前状态的典型特征，常使糖尿病的自然病程复杂化。在尿毒症中，存在出血倾向，主要涉及止血的初级阶段。因此，在糖尿病源性尿毒症患者中，会出现两种相反的止血改变同时存在的罕见情况。在尿毒症患者中，心血管事件的发生率和相关死亡率会增加。这种现象在糖尿病源性尿毒症中会大大加剧。钙稳态是血小板功能的一个关键方面，最近已在人类疾病中有所研究。本研究的目的是评估糖尿病源性和非糖尿病源性尿毒症患者血小板中的钙稳态。

研究设计与方法

我们使用Fura 2评估了18例糖尿病源性尿毒症患者、12例非糖尿病源性尿毒症患者和16名健康对照者血小板中游离钙离子浓度（[Ca2+]i）。在静息状态下以及用0.05、0.1、0.5 U/ml凝血酶刺激后评估[Ca2+]i。

结果

糖尿病源性尿毒症患者的血小板静息[Ca2+]i高于对照者（P = 0.01）和非糖尿病性尿毒症患者（P = 0.001）。同样，在用凝血酶刺激后，糖尿病源性尿毒症患者血小板中[Ca2+]i的绝对增加量高于对照者和非糖尿病性尿毒症患者（P < 0.05）。在弱强度或中等强度凝血酶刺激后，尿毒症患者血小板中[Ca2+]i的相对增加量高于正常水平（P < 0.05）。[Ca2+]i值与其他可能与血小板功能亢进相关的临床和实验室变量之间无相关性。