The Relationship Between Diabetes And Cerebral Atherosclerosis

Part 1 The relationship between type 2 diabetes and cerebral atherosclerosis in the patients with ischemic strokeObjection:The study aimed to investigate whether type 2 diabetes is associated with cerebral atherosclerosis in the patients with ischemic stroke.Methods:A total of 1521 consecutive patients with acute ischemic stroke and with complete digistal subreaction angiography（DSA）data were selected from the Nanjing Stroke Registry System between January 2009 and December 2012.All the patients were classified into two groups based on their most severe cerebral atherosclerotic stenosis by DSA:non-stenosis group（stenosis less than 30%）and stenosis group（stenosis between 30%and 100%）.Results:In the included 1521 subjects,there were 1256（82.58%）patients in the stenosis group and 265（17.43%）in the non-stenosis group.The mean age of the stenosis group was older than the non-stenosis group（P<0.05）.The prevalence of diabetes,hyperlipidemia,and prior ischemic stroke or transient ischemia attack（TIA）in the stenosis group were significantly higher than in the non-stenosis group（all P<0.05）.The plasma levels of HbAlc,LDL-C and fibrinogen（FIB）in the stenosis group were significantly higher than in the non-stenosis group（all P<0.05）,while the plasma level of HDL-C was significant lower in the stenosis group than in non-stenosis group（P<0.05）.Multivariate logistic analysis showed that the advanced age,diabetes,hyperlipidemia,the increased level of HbAlc and FIB were the independent risk factors for cerebral atherosclerosis（all P<0.05）.Conclusions:Type 2 diabetes and increased plasma level of HbAlc are independent risk factors for cerebral atherosclerosis.In addition,advanced age,hyperlipidemia and the increased plasma level of FIB are are independent risk factors for cerebral atherosclerosis.Part 2 The effect of type 2 diabetes on the distribution of cerebral atherosclerosis in the patients with ischemic strokeObjection:This study aimed to investigate the effect of type 2 diabetes on the distribution of cerebral atherosclerosis in the patients with ischemic stroke.Methods:A total of 1256 consecutive patients with acute ischemic stroke who were all confirmed by DSA to have one more cerebral atherosclerotic stenosis（>30%）were selected from the Nanjing Stroke Registry System between January 2009 and December 2012.The included subjects were classified into diabetes and non-diabetes group,and were also divided into the isolated intracranial atherosclerotic stenosis（ICA）,the isolated extracranial atherosclerotic stenosis（ECA）and the combined intracranial and extracranial atherosclerotic stenosis（CCA）group.Results:In the included 1256 subjects,there were 418（33.29%）with diabetes and 838（66.72%）without diabetes;and there were also 407（32.4%）with ECA,352（28.0%）with ICA,and 497（39.6%）with CCA.The mean number of cerebral atherosclerotic stenois and branches affected by the cerebral atherosclerotic stenosis were significantly more in the diabetes group than in non-diabetes group（all P<0.05）.The frequency of CCA and the combined anterior and posterior circulation atherosclerotic stenosis were significant higher in the diabetes group than in the non-diabetes group（all P<0.05）.After adjusting for gender,age,smoking,drinking,hypertension,hyperlipidemia,previous TIA or ischemic stroke and history of coronary heart disease using logistic regression model,DM was an independent risk factor for the extension of cerebral atherosclerotic stenosis（≥3 stenosis）.When using ECA as a reference in the multiple logistic regression analysis,DM was independently associated with both ICA and CCA;The decreased plasma level of HbA1c was not independently associated with CCA,but with ICA.In addition,among the ECA,ICA and CCA groups,the age of ICA was the youngest;male was the strongest predictor for ECA,and the history of TIA or ischemic stroke was stronger predictor for ECA than for ICA;advanced age,hypertension,diabetes,the history of TIA or ischemic stroke,the increased level of LDL-C and the decreased level of HDL-C were all independent rick factors for CCA.Conclusions:Type 2 diabetes tends to cause more extensive cerebral atherosclerosis in the patients with ischemic stroke.It is also the dependent risk factor for ICA and CCA.Part 3 The oxidative stress and epithelial cell apoptosis of carotid arteries in INK2AKITA miceObjection:This study aimed to the oxidative stress and epithelial cell apoptosis of carotid arteries in INK2AKITA mice.Methods:Animals were divided into 3 groups in this study.The 1st group（control group）was C57BL/6 wild type male mice;the 2nd group（diabetes group）was INS2^AKITA male mice,given intraperitoneal injection of 0.9%normal saline（NS）each day for 8 weeks;the 3rd group（Edaravone group）were INS2^AKITA male mice,given intraperitoneal injection of edaravone 9mg/kg each day for consecutive 8 weeks.Then the mice were killed.Serum malondialdehyde（MDA）,nitric oxide（NO）and total nitric oxide synthase（TNOS）were measured.The apoptosis ratio of epithelial cell of carotid arteries was determined using TdT dUTP nick end labelling（TUNEL）.The expression of the proteins including Bcl-2,Bax and Caspase-3 in carotid arteries was measured by immunohistochemistry and Western blot.Results:Compared to the wild type mice,the diabetes mice showed an increase of serum MDA and decrease of NO and NOS;Edaravone-treated diabetes mice significantly decreased serum MDA,increased serum NO and NOS（all P<0.05）.Compared to the wile type mice,the diabetes mice exhibited an increased in the ratio of epithelial cell apoptosis and the expression of Bax and Caspase-3 and a decrease in the expression of Bcl-2 in carotid arteies,but the treatment of diabetes mice with edaravone significantly decreased the ratio of epithelial cell apoptosis and the expression of Bax and Caspase-3 and increased the expression of Bcl-2 in carotid arteries.Conclusions:Diabetes can increase the apoptosis of epithelial cell in large vessels by increasing oxidative stress,and Edaravone can decrease the apoptosis of epithelial cell in large vessels by decreasing oxidative stress in diabetes.