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        血清基質(zhì)細(xì)胞衍生因子—1水平對(duì)阿卡波糖治療初發(fā)2型糖尿病效果的影響

        2017-05-11 21:46:33甘美舍周鳳燕鄭程何明杰
        關(guān)鍵詞:波糖阿卡尿素氮

        甘美舍+周鳳燕+鄭程+何明杰

        [摘要] 目的 探討血清基質(zhì)細(xì)胞衍生因子-1(SDF-1)水平對(duì)阿卡波糖治療初發(fā)2型糖尿病效果的影響。 方法 選取2013年6月~2015年12月廣西壯族自治區(qū)百色市人民醫(yī)院內(nèi)分泌科收治的初發(fā)2型糖尿病患者64例為研究對(duì)象。所有患者均予以口服阿卡波糖50 mg,每日3次,療程持續(xù)6個(gè)月。采用酶聯(lián)免疫吸附試驗(yàn)測(cè)定患者治療前SDF-1水平,并以中位數(shù)155.86 pg/mL為分界值,將患者分為高SDF-1組(21例)和低SDF-1組(43例),比較不同SDF-1水平對(duì)阿卡波糖治療初發(fā)2型糖尿病臨床效果的影響。 結(jié)果 低SDF-1組的總有效率為97.67%,顯著高于高SDF-1組的80.95%,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。低SDF-1組空腹血糖和餐后2 h血糖均明顯低于高SDF-1組,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。兩組肌酐、尿素氮比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05)。 結(jié)論 低水平SDF-1的初發(fā)2型糖尿病患者予以阿卡波糖治療的臨床效果更為良好。

        [關(guān)鍵詞] 基質(zhì)細(xì)胞衍生因子-1;阿卡波糖;初發(fā)2型糖尿?。慌R床療效

        [中圖分類號(hào)] R587.1 [文獻(xiàn)標(biāo)識(shí)碼] A [文章編號(hào)] 1673-7210(2017)03(c)-0059-03

        Effect of serum stromal cell derived factor -1 level on the clinical efficacy of Acarbose in the treatment of newly diagnosed type 2 diabetes

        GAN Meishe1 ZHOU Fengyan1 ZHENG Cheng2 HE Mingjie3

        1.Department of Endocrinology, People's Hospital of Baise City, Guangxi Zhuang Autonomous Region, Baise 533000, China; 2.Department of Andriatry, the First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning 530021, China; 3.Department of Endocrinology, Affiliated Hospital of Youjiang Medical Universtiy for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China

        [Abstract] Objective To explore the effect of serum stromal cell derived factor-1 (SDF-1) level on the clinical efficacy of acarbose in the treatment of newly diagnosed type 2 diabetes. Methods 64 cases of newly diagnosed type 2 diabetes from June 2013 to December 2015 in Department of Endocrinology, People's Hospital of Baise City, Guangxi Zhuang Autonomous Region were selected as study subjects. All patients were given 50 mg Acarbose, 3 times a day and lasted for 6 months. Enzyme linked immunosorbent assay was used to measure the level of SDF-1 before treatment, and the median 155.86 pg/mL was used as the cut-off value. The patients were further divided into high SDF-1 group (21 cases) and low SDF-1 group (43 cases). The effects of SDF-1 levels on clinical efficacy of Acarbose in the treatment of type 2 diabetes were compared. Results Total effective rate in low SDF-1 group was 97.67%, significantly higher than that in high SDF-1 group (80.95%) (P < 0.05). Fasting blood glucose and 2 h postprandial blood glucose in lower SDF-1 group were significantly lower than those in high SDF-1 group (P < 0.05). There was no significant difference in serum creatinine and urea nitrogen between two groups (P > 0.05). Conclusion Clinical efficacy of Acarbose is much better in the newly diagnosed type 2 diabetic patients with low level of SDF-1.

        [Key words] Stromal cell derived factor-1; Acarbose; Newly diagnosed type 2 diabetes; Clinical efficacy

        全球2型糖尿病患者總數(shù)已超過(guò)1.77億例,其中我國(guó)的發(fā)病數(shù)高居第三位[1-2]。阿卡波糖是一種新型口服降糖藥,具有顯著抑制餐后血糖的作用[3-5]?;|(zhì)細(xì)胞衍生因子-1(SDF-1)是一種新發(fā)現(xiàn)的趨化因子,被發(fā)現(xiàn)與糖尿病的多種并發(fā)癥緊密相關(guān)[6]。然而,SDF-1水平是否影響阿卡波糖對(duì)初發(fā)2型糖尿病的治療效果目前尚不清楚。故本研究擬以初發(fā)2型糖尿病患者為研究對(duì)象,探討SDF-1水平對(duì)初發(fā)2型糖尿病臨床療效的影響。

        1 資料與方法

        1.1 一般資料

        選取2013年6月~2015年12月于廣西壯族自治區(qū)百色市人民醫(yī)院內(nèi)分泌科診治的64例初發(fā)2型糖尿病患者為研究對(duì)象。其中男38例,女26例,年齡41~70歲,平均(53.61±5.83)歲。納入標(biāo)準(zhǔn):①所有患者均符合1999年世界衛(wèi)生組織制訂的糖尿病診斷標(biāo)準(zhǔn)[7],且初次診斷2型糖尿??;②心、肺、肝、腎功能均無(wú)明顯異常,糖化血紅蛋白(HbA1c)基線值為7.5%~9.0%;體質(zhì)指數(shù)在20~24 kg/m2;③依從性好,愿意按時(shí)服藥及復(fù)診;④近8周內(nèi)血壓控制平穩(wěn),飲食、運(yùn)動(dòng)較規(guī)律,且無(wú)影響精神或情緒的重大生活事件發(fā)生。排除標(biāo)準(zhǔn):①1型糖尿病患者或合并糖尿病急性并發(fā)癥;②伴有嚴(yán)重感染,罹患呼吸、消化、循環(huán)系統(tǒng)基礎(chǔ)疾病或有精神障礙、神經(jīng)疾病者;③妊娠或哺乳期女性;④治療過(guò)程中不參照規(guī)定服藥,自行服用其他降糖藥物或調(diào)整用藥劑量;⑤治療過(guò)程中失訪者;⑥對(duì)阿卡波糖使用有禁忌證者。研究方案經(jīng)醫(yī)院倫理委員會(huì)批準(zhǔn),所有患者及其家屬均簽署知情同意書。

        所有患者血清SDF-1水平范圍114.19~324.52 pg/mL,平均(194.54±62.81)pg/mL。以SDF-1測(cè)定中位數(shù)155.86 pg/mL為分界值,將患者分為高SDF-1組(21例)和低SDF-1組(43例)。兩組患者一般臨床資料比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05),具有可比性。見(jiàn)表1。

        1.2 治療方法

        所有患者均予以口服阿卡波糖(華東醫(yī)藥股份有限公司制造分公司,生產(chǎn)批號(hào)132402)50 mg,每日3次;服藥期間每2周檢測(cè)一次空腹血糖值和餐后血糖;每8周測(cè)定1次HbA1c的變化量,療程持續(xù)6個(gè)月。

        1.3 療效評(píng)估

        所有患者臨床總體療效依據(jù)HbA1c水平[8]判定,①顯效:HbA1c下降≥1%;②有效:HbA1c下降0.3%~1%;③無(wú)效:HbA1c下降<0.3%??傆行?顯效+有效。觀察患者血糖(空腹血糖、餐后2 h血糖)、肌酐、尿素氮水平。

        1.4 SDF-1水平檢測(cè)

        治療前采集患者清晨空腹靜脈血液,采用酶聯(lián)免疫吸附試驗(yàn)測(cè)定血清SDF-1的變化水平,試劑盒購(gòu)自于上海研卉生物科技有限公司,產(chǎn)品編號(hào)P90122 Hu01,檢測(cè)過(guò)程由專業(yè)檢驗(yàn)人員嚴(yán)格按照說(shuō)明書操作完成。

        1.5 統(tǒng)計(jì)學(xué)方法

        采用SPSS 18.0統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行分析和處理,計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,采用獨(dú)立樣本Student-t檢驗(yàn),計(jì)數(shù)資料采用χ2檢驗(yàn),以P < 0.05為差異有統(tǒng)計(jì)學(xué)意義。

        2 結(jié)果

        2.1 兩組患者療效比較

        低SDF-1組總有效率高于高SDF-1組,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05)。見(jiàn)表2。

        2.2 兩組患者血糖、肌酐和尿素氮水平比較

        低SDF-1組空腹血糖和餐后2 h血糖均明顯低于高SDF-1組(P < 0.05);兩組肌酐、尿素氮比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P > 0.05)。見(jiàn)表3。

        表3 兩組患者血糖、肌酐和尿素氮水平比較(x±s)

        3 討論

        2型糖尿病在我國(guó)是僅次于惡性腫瘤和心血管疾病后的第三大死因[9-10]。當(dāng)前,多數(shù)2型糖尿病患者主要采用雙胍類、α糖苷酶抑制劑、磺酰脲類、胰島素增敏劑等藥物進(jìn)行治療[11-13]。其中,阿卡波糖就是一種新型的α糖苷酶抑制劑,能夠降低空腹血糖、餐后血糖和HbA1c水平[14-15]。本研究結(jié)果顯示,經(jīng)阿卡波糖治療后,兩組患者僅5例無(wú)效,治療總體有效率達(dá)92.18%,與既往報(bào)道結(jié)論基本一致[16]。同時(shí),在治療過(guò)程中,患者均未出現(xiàn)明顯的藥物不良反應(yīng)癥狀,充分提示阿卡波糖對(duì)2型糖尿病具有良好的臨床療效且安全性良好。

        SDF-1是一種由骨髓基質(zhì)細(xì)胞釋放的新型細(xì)胞趨化因子[17]。目前已有眾多研究顯示,SDF-1可廣泛參與新生血管形成、慢性炎癥和氧化應(yīng)激等多種病理生理過(guò)程[18-19]。而且,研究發(fā)現(xiàn),SDF-1水平還與糖尿病的發(fā)生、發(fā)展以及并發(fā)癥緊密相關(guān)[20-21],提示SDF-1可能參與調(diào)節(jié)糖尿病的形成和預(yù)后。本研究以血清SDF-1的中位數(shù)為臨界值,將患者分為高、低SDF-1組,結(jié)果顯示,低SDF-1組患者的總體有效率為97.67%,顯著高于高SDF-1組的80.95%,表明SDF-1水平越低,阿卡波糖對(duì)2型糖尿病患者的療效越佳。研究結(jié)果還發(fā)現(xiàn),阿卡波糖良好的臨床效果并不受年齡、性別、體重指數(shù)、是否吸煙和飲酒等因素的影響,提示SDF-1具有指示阿卡波糖治療2型糖尿病臨床療效的潛在作用。本研究還進(jìn)一步觀察了不同SDF-1水平對(duì)空腹血糖、餐后2 h血糖、肌酐和尿素氮水平的影響,結(jié)果顯示,低SDF-1組患者的空腹血糖和餐后2 h血糖值均明顯低于高SDF-1組,充分證實(shí)了阿卡波糖的療效。但研究結(jié)果卻發(fā)現(xiàn),SDF-1水平對(duì)肌酐和尿素氮的水平無(wú)顯著影響,這可能與SDF-1主要作用靶點(diǎn)在腸道而對(duì)腎臟功能并無(wú)明顯干預(yù)效應(yīng)有關(guān)[22]。

        綜上所述,低水平SDF-1的初發(fā)2型糖尿病患者予以阿卡波糖治療的效果更為良好。但由于研究納入的樣本量有限,觀察周期較短,且未考慮其他使用藥物對(duì)阿卡波糖療效的影響,故研究結(jié)論仍有一定的局限性,亟待后續(xù)多中心臨床試驗(yàn)或基礎(chǔ)研究加以論證。

        [參考文獻(xiàn)]

        [1] Group IDFGD. Global guideline for type 2 diabetes-diabetes research and clinical practice [J]. Diabetes Res Clin Pr,2014,104(1):1-52.

        [2] Association AD. The prevention or delay of type 2 diabetes [J]. Diabetes Care,2015,38(Suppl 1):742-749.

        [3] Yang W,Liu J,Shan Z,et al. Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes:an open-label,non-inferiority randomised trial [J]. Lancet Diabetes Endo,2014,2(1):46-55.

        [4] 牟敏.阿卡波糖、二甲雙胍聯(lián)合胰島素類似物治療肥胖2型糖尿病的短期效果分析[J].中國(guó)當(dāng)代醫(yī)藥,2015,22(22):112-114.

        [5] 高紅彥.阿卡波糖干預(yù)治療糖耐量異常的臨床效果[J].中國(guó)當(dāng)代醫(yī)藥,2016,23(4):120-122.

        [6] Derakhshan R,Arababadi MK,Ahmadi Z,et al. Increased circulating levels of SDF-1(CXCL12)in type 2 diabetic patients are correlated to disease state but are unrelated to polymorphism of the SDF-1β gene in the Iranian population [J]. Inflammation,2012,35(3):900-904.

        [7] Gabir MM,Hanson RL,Dabelea D,et al. The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes [J]. Diabetes Care,2000,23(8):1108-1112.

        [8] D′Emden MC,Shaw JE,Jones GR,et al. Use of glycated haemoglobin(HbA1c)in the diagnosis of diabetes mellitus [J]. Med J Australi,2015,203(2):89-90.

        [9] Xu Y,Wang L,He J,et al. Prevalence and control of diabetes in Chinese adults [J]. JAMA,2013,310(9):948-959.

        [10] Li MZ,Su L,Liang BY,et al. Trends in prevalence,awareness,treatment,and control of diabetes mellitus in mainland china from 1979 to 2012 [J]. Int J Endo,2013,2013(4):753150.

        [11] Asche C,Lafleur J,Conner C. A review of diabetes treatment adherence and the association with clinical and economic outcomes [J]. Clin Ther,2011,33(1):74-109.

        [12] Ratner RE,Sathasivam A. Treatment recommendations for prediabetes [J]. Med Clin N Am,2011,95(2):385-395.

        [13] Pratley RE. The early treatment of type 2 diabetes [J]. Am J Med,2013,126(9):2-9.

        [14] Wang JS,Huang CN,Hung YJ,et al. Acarbose plus metformin fixed-dose combination outperforms acarbose monotherapy for type 2 diabetes [J]. Diabetes Res Clin Pr,2013,102(1):16-24.

        [15] Hanefeld M,Schaper F. Acarbose:oral antidiabetes drug with additional cardiovascular benefits [J]. Exp Rev Cardiovasc Ther,2014,6(2):153-163.

        [16] Hu R,Li Y,Lv Q,et al. Acarbose monotherapy and type 2 diabetes prevention in eastern and western prediabetes:an ethnicity-specific Meta-analysis [J]. Clin Ther,2015,37(8):1798-1812.

        [17] Yousry S,Shahin G,Demerdash DE,et al. SDF-1(CXCL12)polymorphisms in Egyptian patients with systemic lupus erythematosus(SLE):a pilot study [J]. Comp Clin Pathol,2015,24(6):1535-1540.

        [18] Cai Y,Li X,Wang YS,et al. Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells [J]. Exp Eye Res,2014, 123(4):87-96.

        [19] Olekson MA,F(xiàn)aulknor R,Bandekar A,et al. SDF-1 liposomes promote sustained cell proliferation in mouse diabetic wounds [J]. Wound Repair Regen,2015,23(5):711-723.

        [20] Fadini GP,Albiero M,Seeger F,et al. Stem cell compartmentalization in diabetes and high cardiovascular risk reveals the role of DPP-4 in diabetic stem cell mobilopathy [J]. Basic Res Cardiol,2013,108(1):1164.

        [21] Zhao Y,Tan Y,Xi S,et al. A novel mechanism by which SDF-1β protects cardiac cells from palmitate-induced endoplasmic reticulum stress and apoptosis via CXCR7 and AMPK/p38 MAPK-mediated interleukin-6 generation [J]. Diabetes,2013,62(7):2545.

        [22] Connelly KA,Advani A,Zhang Y,et al. DPP-4 inhibition improves cardiac function in experimental myocardial infarction:role of SDF-1 alpha [J]. J Diabetes,2015,8(1):1-8.

        (收稿日期:2016-12-16 本文編輯:李亞聰)

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