冉卡娜， 張?jiān)茟c， 徐 剛， 方永碧， 周 沁

(1.重慶市南桐礦業(yè)公司總醫(yī)院內(nèi)分泌科, 重慶 400800 2.重慶市醫(yī)科大學(xué)附屬第二醫(yī)院內(nèi)分泌科, 重慶 400000)

臨床研究

短期胰島素強(qiáng)化治療對(duì)2型糖尿病患者血糖長(zhǎng)期控制的效果

冉卡娜1， 張?jiān)茟c1， 徐 剛1， 方永碧1， 周 沁2

(1.重慶市南桐礦業(yè)公司總醫(yī)院內(nèi)分泌科, 重慶4008002.重慶市醫(yī)科大學(xué)附屬第二醫(yī)院內(nèi)分泌科, 重慶400000)

目的探討短期胰島素強(qiáng)化治療對(duì)2型糖尿病患者血糖長(zhǎng)期控制的效果。方法選取2015年1月至2016年12月內(nèi)分泌科收治的120例2型糖尿病患者為研究對(duì)象，分層隨機(jī)法將兩組患者分為對(duì)照組和觀察組，每組各60例；兩組患者均進(jìn)行糖尿病教育，并從飲食和運(yùn)動(dòng)方面進(jìn)行調(diào)整治療，對(duì)照組在調(diào)整治療的基礎(chǔ)上采用二甲雙胍進(jìn)行常規(guī)治療，觀察組在調(diào)整治療的基礎(chǔ)上再聯(lián)合胰島素進(jìn)行強(qiáng)化治療，每日三餐前30min皮下注射諾和靈R(短效胰島素)，睡前皮下注射諾和靈N(中效胰島素)，胰島素劑量根據(jù)血糖控制情況進(jìn)行調(diào)整，連續(xù)治療1個(gè)月。定期隨訪3個(gè)月，比較兩組空腹胰島素(FINS)、胰島素抵抗指數(shù)(HOMA-IR)、空腹C肽(FC-P)、餐后2h C肽(2h C-P)、餐后2h胰島素(2 hINS)水平以評(píng)估胰島β細(xì)胞功能；比較空腹血糖(FBG)、2hPG(餐后2h血糖)、糖化血紅蛋白(HbA1C)水平及記錄不良反應(yīng)情況。結(jié)果治療后，F(xiàn)INS、FC-P、2h C-P、2 hINS均較治療前升高，且觀察組更高，差異有統(tǒng)計(jì)學(xué)意義，P<0.05；治療后兩組HOMA-IR均較治療前低，且觀察組更低，差異有統(tǒng)計(jì)學(xué)意義，P<0.05；兩組患者治療前FBG、2hPG、HbA1C比較無(wú)明顯差異，治療后，兩組FBG、2hPG、HbA1C水平均有所下降，且觀察組更低，差異有統(tǒng)計(jì)學(xué)意義；兩組患者均未見心肝腎功能損傷，對(duì)照組無(wú)明顯不良反應(yīng)，治療組1例患者出現(xiàn)低血糖表現(xiàn)。結(jié)論短期胰島素強(qiáng)化治療可以改善2型糖尿病患者胰島β細(xì)胞功能，維持其血糖在正常范圍，具有臨床價(jià)值。

短期胰島素強(qiáng)化； 2型糖尿??； 血糖長(zhǎng)期控制

2型糖尿病早期發(fā)病過(guò)程中，機(jī)體可以通過(guò)增加胰島素分泌將血糖維持于正常范圍內(nèi)，若未及時(shí)給予有效治療則會(huì)引起胰島β細(xì)胞功能衰減而造成胰島素分泌下降，最終使血糖水平維持在較高水平而出現(xiàn)各種臨床并發(fā)癥[1～3]。胰島素強(qiáng)化可在短時(shí)間內(nèi)使血糖達(dá)到或接近正常水平，控制血糖對(duì)胰島β細(xì)胞功能及胰島素敏感性將產(chǎn)生有利影響[4]。本試驗(yàn)研究其對(duì)2型糖尿病患者的臨床療效，報(bào)道如下：

1 資料與方法

1.1一般資料:選取本院2015年1月至2016年12月內(nèi)分泌科收治的120例2型糖尿病患者為研究對(duì)象，其中男63例，女57例；年齡35～70在之間，平均年齡為56.08±3.05歲；病程<6月。采用分層隨機(jī)法將120例患者隨機(jī)分為觀察組和對(duì)照組，60例/組，兩組患者一般資料比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，具有可比性。診斷標(biāo)準(zhǔn)采用1999年WHO診斷標(biāo)準(zhǔn)，《中國(guó)高血壓防治指南》高血壓診斷標(biāo)準(zhǔn)[5]。納入標(biāo)準(zhǔn)：①本研究開展之前未用過(guò)降糖藥物；②無(wú)嚴(yán)重軀體疾病；③經(jīng)患者同意并自愿參加本研究。排除標(biāo)準(zhǔn)：①具有糖尿病酮癥酸中毒；②合并有感染、嚴(yán)重腎、心、肝功能不全者；③孕婦及哺乳者。

1.2方法:患者在入院當(dāng)天均進(jìn)行糖尿病教育，并從飲食和運(yùn)動(dòng)方面給予調(diào)整治療。對(duì)照組在調(diào)整治療的基礎(chǔ)上再給予鹽酸二甲雙胍(廠家：天津太平洋制藥有限公司；國(guó)藥準(zhǔn)字號(hào)：H12020797)進(jìn)行常規(guī)治療，0.5g/次，每日3次；觀察組在調(diào)整治療的基礎(chǔ)上再聯(lián)合胰島素進(jìn)行強(qiáng)化治療，具體操作如下：每日三餐前30min皮下注射諾和靈R(短效胰島素)，睡前皮下注射諾和靈N(中效胰島素)，胰島素劑量根據(jù)血糖控制情況進(jìn)行調(diào)整。連續(xù)治療1個(gè)月。

1.3觀察指標(biāo):①治療后定期隨訪3個(gè)月，測(cè)定治療前及治療后3個(gè)月空腹胰島素(FINS)、胰島素抵抗指數(shù)(HOMA-IR)、空腹C肽(FC-P)、餐后2h C肽(2h C-P)、餐后2h胰島素(2 hINS)水平以評(píng)估胰島β細(xì)胞功能比較。②于治療前、治療90天后測(cè)定空腹血糖(FBG)、2hPG(餐后2h血糖)、糖化血紅蛋白(HbA1C)水平；③記錄不良反應(yīng)情況。

2 結(jié) 果

表1 兩組患者治療前后胰島β細(xì)胞功能療效比較

注：*與治療前比較，差異有統(tǒng)計(jì)學(xué)意義，P<0.05；#與對(duì)照組比較，差異有統(tǒng)計(jì)學(xué)意義，P<0.05

2.1兩組患者胰島β細(xì)胞功能比較:治療后，F(xiàn)INS、FC-P、2h C-P、2 hINS均較治療前升高，且觀察組更高，差異有統(tǒng)計(jì)學(xué)意義，P<0.05；治療后兩組HOMA-IR均較治療前低，且觀察組更低，差異有統(tǒng)計(jì)學(xué)意義，P<0.05，具體結(jié)果見表1。

2.2兩組患者治療前后血糖水平比較:兩組患者治療前FBG、2hPG、HbA1C比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，治療后，兩組FBG、2hPG、HbA1C水平均有所下降，且觀察組更低，差異有統(tǒng)計(jì)學(xué)意義，具體比較結(jié)果見表2。

表2 兩組患者治療前后血糖比較

注：*與治療前比較，差異有統(tǒng)計(jì)學(xué)意義，P<0.05；#與對(duì)照組比較，差異有統(tǒng)計(jì)學(xué)意義，P<0.05

2.3兩組患者不良反應(yīng)比較：兩組患者均未見心肝腎功能損傷，對(duì)照組無(wú)明顯不良反應(yīng)，治療組1例患者出現(xiàn)低血糖表現(xiàn)。

3 討 論

糖尿病是一種由多種因素造成胰島素絕對(duì)或相對(duì)分泌不足，以糖耐量減低、血糖增高及尿糖為主要特征的代謝性疾病[6,7]，流行病學(xué)研究證實(shí)，現(xiàn)階段我國(guó)糖尿病患病率較高，約6.09%[8]。胰島素抵抗和胰島β細(xì)胞功能障礙是引起糖尿病的主要原因，可引起胰島素分泌量和質(zhì)的異常[9～11]。胰島β細(xì)胞功能損傷是2型糖尿病患者可逆性病理改變，既可作為糖尿病的發(fā)展結(jié)果，也可以成為糖尿病的發(fā)展原因，可相互作用形成惡性循環(huán)推進(jìn)病理進(jìn)程[12～14]。早期有效干預(yù)措施可以有效緩解胰島β細(xì)胞功能損傷甚至逆向改變。

臨床工作者往往采取階梯式療法治療2型糖尿病患者，胰島素治療是最后的方法，這種方法導(dǎo)致糖尿病患者長(zhǎng)期處于血糖控制不佳狀態(tài)，并且增加了糖尿病患者心、腦、腎病理過(guò)程的發(fā)生風(fēng)險(xiǎn)，對(duì)預(yù)后非常不利。

本研究顯示治療后，F(xiàn)INS、FC-P、2h C-P、2 hINS均較治療前升高，且觀察組更高；兩組HOMA-IR均較治療前低，且觀察組更低；兩組FBG、2hPG、HbA1C水平均有所下降，且觀察組更低；兩組患者均未見心肝腎功能損傷，對(duì)照組無(wú)明顯不良反應(yīng)，治療組1例患者出現(xiàn)低血糖表現(xiàn)。有研究顯示，短期胰島素強(qiáng)化能在短時(shí)間內(nèi)解除高糖毒性及脂毒性對(duì)胰島β細(xì)胞的抑制作用，而且能夠迅速降低血糖。本研究顯示觀察組患者血糖及糖化血紅蛋白控制較好，部分學(xué)者認(rèn)為糖化血紅蛋白控制在6.5%以下可以預(yù)防大血管并發(fā)癥的發(fā)生，但是，口服降糖藥物很難使HbA1C下降到7%以下，然而胰島素降血糖的作用是持續(xù)的，在一定時(shí)間內(nèi)可以保護(hù)或逆轉(zhuǎn)胰島β細(xì)胞功能的衰變。這可能是觀察組較對(duì)照組HbA1C水平低的原因。已有研究報(bào)道短期胰島素強(qiáng)化治療，可以恢復(fù)胰島β細(xì)胞功能恢復(fù)，停藥后仍可維持幾周，這可能是治療后觀察組患者FINS、FC-P、2h C-P、2 hINS水平較對(duì)照組高的原因之一。型糖尿病患者第一時(shí)相胰島素分泌，并對(duì)第二時(shí)相胰島素分泌及最大分泌量有所改善。

本研究證實(shí)無(wú)論是從長(zhǎng)期血糖控制方面還是胰島β細(xì)胞功能保護(hù)方面，短期胰島素強(qiáng)化均優(yōu)于口服降糖藥物。但本研究例數(shù)較少，下一步研究可以多中心聯(lián)手，收集更多病例數(shù)，為短期胰島素強(qiáng)化治療2型糖尿病患者提供更加可靠的證據(jù)。

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EffectofShortTermIntensiveInsulinTherapyonBloodGlucoseinPatientswithType2Diabetes

RANKana,ZHANGYunqing,XUGang,etal

(TheGeneralHospitalofNantongMiningCompany,Chongqing400800,China)

Objective:To investigate the effect of short term intensive insulin therapy on blood glucose in patients with type 2 diabetes.Methods120 cases of type 2 diabetic patients were Selected from January 2015 to December 2016 in Department of Endocrinology as the object of study. Patients were divided into control and observation group by stratified randomization, 60 cases in each group. Patients in the two groups were underwent diabetic education and diet, exercise therapy; Based on the routine therapy, patients in the control group were given metformin therapy; patients in the observation group were given islet hormone intensive therapy, such as subcutaneous injection Novolin R (short acting insulin ), three times daily, 30 minutes before meals and subcutaneous injections Novolin N (acting insulin)three times daily before bedtime. Based on the glycemic control to adjust the dose of insulin, continuous treatment for 1 month. Regular follow-up 3 months, fasting insulin (fins), insulin resistance index (HOMA-IR), fasting C peptide (fc-p), postprandial 2H C-peptide (2H C-P), postprandial 2 h insulin level (Hins)were compared between the two groups to assess islet beta cell function; Besides, fasting blood glucose (FBG), 2hPG (2 h postprandial blood glucose, glycosylated hemoglobin (HbA1c) level and the adverse reactions were also compared.ResultsAfter treatment, fins, fc-p, 2h C-P, 2 Hins significantly increased that compared with before treatment, and higher significant increasing at observation group, the difference were statistically significant (P<0.05). After treatment, HOMA-IR level in patients of the two group was decreased that compared with before treatment, and more lower values was observed at observation group, the difference was statistically significant (P < 0.05). Before treatment, the levels of FBG, 2Hpg and HbA1c in patients of the two groups were not significantly different; While, they were significantly decreased and more lower values observed at observation group, the difference was statistically significant. There were no obvious heart, liver and kidney function damage in patients of the two groups and without obvious adverse reactions in the control group, only 1 patient appeared low blood sugar glucose.ConclusionShort term intensive insulin therapy can improve islet beta cell function in patients with type 2 diabetes mellitus, and maintain the normal range of blood glucose, which is of clinical value.

Short term intensive insulin; Type 2 diabetes mellitus; Blood glucose control

A

10.3969/j.issn.1006-6233.2017.10.034

1006-6233(2017)10-1699-04

重慶市自然科學(xué)基金項(xiàng)目，(編號(hào)：2010JJ1561)