Hyperinsulinism and cerebral microangiopathy.
Hyperinsulinism and cerebral microangiopathy.
复制标题
高胰岛素血症和脑微血管病。
作者：
P. Zunker;A. Schick;H. C. Buschmann;D. Georgiadis;D. Nabavi;M. Edelmann;E. Ringelstein
背景和目的
高胰岛素水平是公认的动脉粥样硬化的危险因素。微血管内皮细胞比大血管内皮细胞对胰岛素的代谢和促有丝分裂作用更敏感。除了导致动脉粥样硬化的作用外，高水平的胰岛素还通过增强纤溶酶原激活物抑制物-1来损害纤溶系统。我们开展这项研究是为了评估这一假设，即血清胰岛素和C-肽水平升高与脑小血管疾病有关，而不是大血管病变。
方法
连续194例出现症状性脑血管疾病的患者被分为三个亚组，根据临床表现、脑成像检查以及颅外和经颅血管超声结果进行区分：(1)腔隙患者(n=20)，(2)皮质下动脉硬化性脑病(n=35)，(3)大血管疾病引起的中风(n=99)。有隐源性(n=9)或心源性(n=16)卒中或表现出微血管病变组和大血管病变组(n=15)特征的患者不再接受进一步评估。并对30例无脑血管病表现的患者进行了检查。测定所有受试者的空腹血糖、胰岛素和C-肽水平。
结果
三组患者的年龄和性别与对照组相比无显著差异。腔隙组胰岛素水平显著高于皮质下动脉硬化性脑病组、大血管病变组和对照组(中位数[四分位数范围]分别为：103.8[四分位数范围]：103.8[198.6]，72.0[103.2]，66.0[57.0]，52.2pmoL/L；均P<；0.05，Mann-Whitney检验)。微血管病变组(皮质下动脉硬化性脑病和腔隙)与大血管病变组和对照组之间的胰岛素浓度差异有统计学意义(分别为81.0[110.4]、66.0[57.0]和55.2pmol/L；均P<；0.05，Mann-Whitney)。C-肽水平和血糖值的分布也是如此，但这些差异没有达到统计学意义。
结论
胰岛素水平升高可能是脑部小血管疾病发展的致病因素，主要发生在存在腔隙的患者中。这是否仅仅是由于穿透小动脉的动脉粥样硬化改变，或者血液流变学的改变是否也是可操作的，仍有待评估。
BACKGROUND AND PURPOSE
High insulin levels are a recognized risk factor for atherosclerosis. Microvascular endothelium is more susceptible to metabolic and mitogenic effects of insulin than large-vessel endothelium. Besides their atherogenic effect, high insulin levels impair fibrinolysis by enhancing plasminogen activator inhibitor-1. We undertook this study to evaluate the hypothesis that elevated serum insulin and C-peptide levels are related to cerebral small-vessel disease rather than large-vessel pathology.
METHODS
One hundred ninety-four consecutive patients presenting with symptomatic cerebrovascular disease were assigned to three subgroups that were differentiated by clinical presentations, brain imaging studies, and extracranial as well as transcranial vascular ultrasound findings: (1) patients with lacunes (n = 20), (2) patients with subcortical arteriosclerotic encephalopathy (n = 35), and (3) patients with strokes due to large-vessel disease (n = 99). Patients who had suffered a cryptogenic (n = 9) or cardioembolic (n = 16) stroke or who showed characteristics of the microangiopathy and macroangiopathy groups (n = 15) were not further evaluated. Thirty patients without manifestations of cerebrovascular disease were also examined. Fasting blood glucose, insulin, and C-peptide levels were determined in all subjects.
RESULTS
There were no significant differences in age or sex among the three groups and control patients. Insulin levels were significantly higher in the lacunar group compared with the subcortical arteriosclerotic encephalopathy group, the macroangiopathy group, and the control patients (median [interquartile range]: 103.8 [198.6], 72.0 [103.2], 66.0 [57.0], and 52.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney test). There was a statistically significant difference in insulin concentrations between the microangiopathy group (subcortical arteriosclerotic encephalopathy and lacunes) and the macroangiopathy and control groups (81.0 [110.4], 66.0 [57.0], and 55.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney). The same was true for the distribution of C-peptide levels and to a minor extent blood glucose values, but these differences failed to reach statistical significance.
CONCLUSIONS
Elevated insulin levels potentially represent a pathogenetic factor in the development of cerebral small-vessel disease, predominantly in patients presenting with lacunes. Whether this is due solely to atherosclerotic changes of the small penetrating arteries or whether changes in hemorheology are operative as well remains to be evaluated.
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DOI：
10.1056/nejm198908243210806
发表时间：
1989-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
K. Johnson;T. O'Brien;C. Betsholtz;P. Westermark
通讯作者：
K. Johnson;T. O'Brien;C. Betsholtz;P. Westermark
内皮细胞和动脉粥样硬化。
DOI：
--
发表时间：
1992
期刊：
Journal of hypertension. Supplement : official journal of the International Society of Hypertension
影响因子：
--
作者：
Badimon,L;Badimon,JJ;Penny,W;Webster,MW;Chesebro,JH;Fuster,V
通讯作者：
Fuster,V
影响因子：
39.2
作者：
WARRAM, JH;MARTIN, BC;KAHN, CR
通讯作者：
KAHN, CR
DOI：
10.1073/pnas.89.15.6998
发表时间：
1992-08-01
影响因子：
11.1
作者：
SCHNEIDERMAN, J;SAWDEY, MS;LOSKUTOFF, DJ
通讯作者：
LOSKUTOFF, DJ