老年女性代謝綜合征患者血清25-羥維生素D水平變化及臨床意義研究

褚 琳，孫 芳，劉 杰，陳陵霞，苗懿德

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·論著·

老年女性代謝綜合征患者血清25-羥維生素D水平變化及臨床意義研究

褚 琳，孫 芳，劉 杰，陳陵霞，苗懿德

目的 探討老年女性患者25-羥維生素D〔25-(OH)VD〕水平與代謝綜合征(MS)發(fā)生發(fā)展的相關(guān)性。方法 收集2011年9月—2013年11月于北京大學(xué)人民醫(yī)院老年科住院的老年女性患者188例，年齡60～94歲，均為絕經(jīng)后。按照有無(wú)MS將患者分為MS組(79例)和非MS組(109例)；按照血清25-(OH)VD中位數(shù)(31.5 nmol/L)將患者分為<31.5 nmol/L組(94例)和≥31.5 nmol/L組(94例)。測(cè)量血壓、身高、體質(zhì)量、計(jì)算體質(zhì)指數(shù)(BMI)，并檢測(cè)空腹血糖(FPG)、總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)、糖化血紅蛋白(HbA1c)、空腹胰島素(FINS)、血鈣(Ca)、血磷(P)、血清25-(OH)VD、骨特異性堿性磷酸酶(BAP)和抗酒石酸酸性磷酸酶(TRAP)水平，計(jì)算胰島素抵抗指數(shù)(HOMA-IR)；比較MS組與非MS組血清25-(OH)VD缺乏程度；分析血清25-(OH)VD與觀察指標(biāo)的相關(guān)性。結(jié)果 MS組高血壓病程、糖尿病病程、TG、HDL-C、FPG、HbA1c、FINS、HOMA-IR與非MS組比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。MS組患者血清25-(OH)VD水平低于非MS組(P<0.05)。<31.5 nmol/L組高血脂病程、TG、HDL-C、FPG、HbA1c、FINS、HOMA-IR與≥31.5 nmol/L組比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)?！?1.5 nmol/L組患者血清25-(OH)VD水平高于<31.5 nmol/L組(P<0.05)。MS組與非MS組血清25-(OH)VD缺乏程度比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。血清25-(OH)VD水平與TG、FPG、HOMA-IR呈負(fù)相關(guān),與HDL-C呈正相關(guān)(P<0.05)。結(jié)論 老年女性患者血清25-(OH)VD水平較低，且與血脂、血糖相關(guān)，為臨床進(jìn)一步研究提供了參考依據(jù)。

代謝綜合征X；老年女性；維生素D

褚琳，孫芳，劉杰，等.老年女性代謝綜合征患者血清25-羥維生素D水平變化及臨床意義研究[J].中國(guó)全科醫(yī)學(xué)，2015，18(12)：1376-1381.[www.chinagp.net]

Chu L，Sun F，Liu J,et al.Changes of serum 25-hydrocyvitamin D level in elderly women with metabolic syndrome and its clinical significance[J].Chinese General Practice，2015，18(12)：1376-1381.

中國(guó)一項(xiàng)大型研究發(fā)現(xiàn)，心血管疾病(cardiovascular disease，CVD)已成為女性死亡的首位原因[1]。有資料顯示，絕經(jīng)后女性CVD發(fā)生率較絕經(jīng)前顯著上升[2]。代謝綜合征(metabolic syndrome，MS)是評(píng)價(jià)CVD高風(fēng)險(xiǎn)的重要指標(biāo)。在亞洲，由于西化飲食的增加和活動(dòng)減少，MS患者的數(shù)量正在顯著增加[3-4]。MS的發(fā)生率在中青年人群中男性普遍高于女性，而這種性別差異在50歲以上人群中則不存在。研究表明，絕經(jīng)后女性是MS的高危人群，絕經(jīng)是MS的危險(xiǎn)因素[5]。

近年來(lái)發(fā)現(xiàn)，維生素D缺乏可能與MS的發(fā)病風(fēng)險(xiǎn)升高相關(guān)[6-9]。有韓國(guó)研究表明，絕經(jīng)后女性維生素D水平與血壓、三酰甘油(TG)和高密度脂蛋白膽固醇(HDL-C)等MS組成部分相關(guān)[10]。目前國(guó)內(nèi)尚無(wú)有關(guān)MS與絕經(jīng)后婦女的血清維生素D缺乏的相關(guān)研究，為此筆者擬通過(guò)檢測(cè)絕經(jīng)后女性MS患者血清25-羥維生素D〔25-(OH)VD〕水平的變化，探討其與MS的關(guān)系。

1 對(duì)象與方法

1.1 研究對(duì)象 收集2011年9月—2013年11月在北京大學(xué)人民醫(yī)院老年科住院的老年女性患者188例，年齡60～94歲，平均(77.1±7.6)歲，均為絕經(jīng)后。納入標(biāo)準(zhǔn)：因2型糖尿病、高血壓、冠狀動(dòng)脈粥樣硬化性心臟病、慢性消化系統(tǒng)疾病、腦供血不足、腔隙性腦梗死等疾病入院的女性患者。排除標(biāo)準(zhǔn)：嚴(yán)重器質(zhì)性內(nèi)分泌疾病者，如甲狀腺疾病、甲狀旁腺功能亢進(jìn)等；繼發(fā)性高血壓、惡性高血壓者；嚴(yán)重肝、腎功能異常者；心臟瓣膜病、心肌疾病者；重度貧血、骨髓瘤等影響骨代謝疾病者；急性感染、惡性腫瘤者；腎切除或維持透析患者；服用活性維生素D藥物，長(zhǎng)期服用激素、免疫抑制劑，使用胰島素等藥物者。

1.2 方法

1.2.1 一般情況 詳細(xì)詢問(wèn)患者病史，入院后檢查血壓〔收縮壓(SBP)，舒張壓(DBP)〕、身高、體質(zhì)量，計(jì)算體質(zhì)指數(shù)(BMI)。

本文要點(diǎn)：

本研究表明在絕經(jīng)后女性中，血清25-(OH)VD水平與MS具有一定相關(guān)性，提示維生素D缺乏可能在絕經(jīng)后人群相關(guān)代謝異常以及CVD發(fā)病過(guò)程中起重要作用。這為指導(dǎo)絕經(jīng)后女性合理補(bǔ)充維生素D提供了參考依據(jù)。

1.2.2 血液學(xué)指標(biāo)檢測(cè) 患者均清晨空腹采取靜脈血2 ml,檢測(cè)總膽固醇(TC)、TG、低密度脂蛋白膽固醇(LDL-C)、HDL-C、空腹血糖(FPG)、糖化血紅蛋白(HbA1c)、血鈣(Ca)、血磷(P)和空腹胰島素(FINS)水平。測(cè)定血清25-(OH)VD、骨特異性堿性磷酸酶(BAP)、抗酒石酸酸性磷酸酶(TRAP)水平等骨轉(zhuǎn)換生化指標(biāo)，采用英國(guó)IDS公司試劑盒。血清25-(OH)VD的批內(nèi)變異為5.6%，批間變異為7.3%。計(jì)算胰島素抵抗指數(shù)(HOMA-IR)=FINS×FPG/22.5。

1.2.3 診斷標(biāo)準(zhǔn)及分組 MS診斷依照中華醫(yī)學(xué)會(huì)糖尿病學(xué)分會(huì)2004年建議適合中國(guó)人群的診斷，具備以下4項(xiàng)中的3項(xiàng)及以上者：(1)超重和/或肥胖：BMI≥25.0 kg/m2；(2)高血糖：FPG≥6.1 mmol/L和/或餐后2 h血糖(2 hPG)≥7.8 mmol/L，和/或已確診為糖尿病并治療者；(3)高血壓：SBP/DBP≥140/90 mm Hg(1 mm Hg =0.133 kPa)，和/或已確診為高血壓并治療者；(4)血脂紊亂：TG≥1.7 mmol/L和/或HDL-C<1.0 mmol/L(女)。血清25-(OH)VD水平分級(jí)標(biāo)準(zhǔn)：(1)缺乏〔25-(OH)VD≤50 nmol/L〕；(2)不足〔50 nmol/L<25-(OH)VD <75 nmol/L〕；(3)充足〔25-(OH)VD≥75 nmol/L〕[11]。按照有無(wú)MS將患者分為MS組(79例)和非MS組(109例)；按照血清25-(OH)VD中位數(shù)(31.5 nmol/L)將患者分為<31.5 nmol/L組(94例)和≥31.5 nmol/L組(94例)。

2 結(jié)果

2.1 MS組與非MS組一般資料比較 MS組高血壓病程、糖尿病病程、TG、HDL-C、FPG、HbA1c、FINS、HOMA-IR與非MS組比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其余各項(xiàng)指標(biāo)比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表1)。

2.2 MS組與非MS組骨生化指標(biāo)比較 MS組患者血清25-(OH)VD水平低于非MS組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其余指標(biāo)比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表2)。

2.3 <31.5 nmol/L組和≥31.5 nmol/L組一般資料比較 <31.5 nmol/L組高血脂病程、TG、HDL-C、FPG、HbA1c、FINS、HOMA-IR與≥31.5 nmol/L組比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其余指標(biāo)比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表3)。

2.4 <31.5 nmol/L組和≥31.5 nmol/L組骨生化指標(biāo)比較 ≥31.5 nmol/L組患者血清25-(OH)VD水平高于<31.5 nmol/L組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；其余指標(biāo)比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見(jiàn)表4)。

Table 2 Comparison of biomechanics index between the MS group and non-MS group

組別例數(shù)25-(OH)VD(nmol/L)TRAP(U/L)BAP(μg/L)Ca(mmol/L)P(mmol/L)非MS組10936.2±14.63.6±1.215.1±8.42.2±0.11.2±0.2MS組7932.8±12.03.6±1.415.5±6.12.2±0.11.2±0.2t值4.1200.2810.5261.5500.023P值0.0320.5970.4690.1190.881

注：25-(OH)VD=25-羥維生素D，TRAP=抗酒石酸酸性磷酸酶，BAP=骨特異性堿性磷酸酶，Ca=血鈣，P=血磷

表1 MS組與非MS組一般資料比較

注：BMI=體質(zhì)指數(shù)，TC=總膽固醇，LDL-C=低密度脂蛋白膽固醇，TG=三酰甘油，HDL-C=高密度脂蛋白膽固醇，F(xiàn)PG=空腹血糖，SBP=收縮壓，DBP=舒張壓，HbA1c=糖化血紅蛋白，F(xiàn)INS=空腹胰島素，HOMA-IR=胰島素抵抗指數(shù)，MS=代謝綜合征

表3 25-(OH)VD<31.5 nmol/L組和≥31.5 nmol/L組一般資料比較

2.5 MS組與非MS組血清25-(OH)VD缺乏程度比較 MS組與非MS組血清25-(OH)VD缺乏程度比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05，見(jiàn)表5)。

2.6 血清25-(OH)VD水平與觀察指標(biāo)的相關(guān)性分析 血清25-(OH)VD水平與TG、FPG、HOMA-IR呈負(fù)相關(guān),與HDL-C呈正相關(guān)(P<0.05)，與其余指標(biāo)無(wú)相關(guān)關(guān)系(P>0.05，見(jiàn)表6)。

Table 4 Comparison of biomechanics index between the 25-(OH)VD <31.5 nmol/L group and ≥31.5 nmol/L group

組別例數(shù)25-(OH)VD(nmol/L)TRAP(U/L)BAP(ug/L)Ca(mmol/L)P(mmol/L)<31.5nmol/L組9425.2±4.63.8±1.516.2±6.62.2±0.11.2±0.2≥31.5nmol/L組9446.2±11.13.4±1.014.2±8.32.2±0.11.2±0.2t值32.6201.1150.5340.0000.072P值<0.0010.2920.4661.0001.000

表5 MS組與非MS組血清25-(OH)VD缺乏程度比較〔n(%)〕

Table 5 Comparison of 25-(OH)VD level between the MS group and non-MS group

組別例數(shù)缺乏不足充足非MS組10979(72.5)25(22.9)5(4.6)MS組 79 69(87.3)9(11.4)1(1.3)u值-2.481P值 0.013

表6 血清25-(OH)VD水平與觀察指標(biāo)的相關(guān)性分析

Table 6 Correlation between serum 25-(OH) VD level and observation index

指標(biāo)r值P值年齡-0.1300.075BMI-0.0580.681高血脂病程-0.1250.315高血壓病程-0.0920.217糖尿病病程-0.0270.711TC-0.1490.061LDL-C-0.1300.074TG-0.2500.015HDL-C0.2260.018FPG-0.1680.034SBP-0.0840.684DBP0.0590.354HbA1c0.1050.191FINS-0.0780.668HOMA-IR-0.1520.042

3 討論

MS指一組由遺傳和環(huán)境因素共同作用引起的多代謝異常性疾病，表現(xiàn)為肥胖、血壓升高、血脂和血糖異常。圍絕經(jīng)期及絕經(jīng)后血清性激素水平的變化，引起了圍絕經(jīng)期的一系列癥狀，也使得MS的患病率較絕經(jīng)前明顯增加。絕經(jīng)后女性MS患病率高達(dá)32.6%～37.3%[12-13]，且其CVD的發(fā)病風(fēng)險(xiǎn)明顯增加[14]。絕經(jīng)后肥胖導(dǎo)致日益加重的胰島素抵抗,可能是絕經(jīng)后女性MS發(fā)病風(fēng)險(xiǎn)增高的關(guān)鍵因素[15]。Kip等[16]研究發(fā)現(xiàn)，在女性人群中，MS而不是BMI預(yù)測(cè)了CVD的危險(xiǎn)性。

維生素D是一種脂溶性維生素。由于25-(OH)VD在血中水平相對(duì)較高，t1/2較長(zhǎng)，因此一般認(rèn)為臨床可以通過(guò)測(cè)定血清25-(OH)VD的水平來(lái)了解體內(nèi)維生素D的營(yíng)養(yǎng)狀況[8]。近年來(lái)發(fā)現(xiàn)，維生素D缺乏可能增加MS的發(fā)病風(fēng)險(xiǎn)[6-9,17]。有研究表明，絕經(jīng)后女性MS組維生素D水平與血壓、TG和HDL-C等相關(guān)[10]。本研究結(jié)果顯示，絕經(jīng)后女性MS組患者25-(OH)VD水平低于非MS組，表明血清25-(OH)VD與MS具有一定相關(guān)性。

多項(xiàng)研究表明，血清維生素D水平與2型糖尿病的發(fā)病率呈負(fù)相關(guān)[18-21]。并有研究發(fā)現(xiàn)，短期補(bǔ)充維生素D能夠改善胰島β細(xì)胞功能，從而降低HbA1c的上升幅度[22-24]。同時(shí)，胰島素抵抗在糖尿病發(fā)生、發(fā)展中起著重要作用。多項(xiàng)研究表明，當(dāng)血清維生素D水平從缺乏補(bǔ)充至充足時(shí)，其胰島素敏感性將會(huì)明顯升高，甚至在提高胰島素敏感性上明顯優(yōu)于曲格列酮及二甲雙胍[23,25-26]。本研究發(fā)現(xiàn)，絕經(jīng)后女性25-(OH)VD與FPG、HOMA-IR相關(guān)，與上述研究結(jié)論相似。

研究發(fā)現(xiàn)，絕經(jīng)后女性TG水平較絕經(jīng)前女性明顯升高[27]。同時(shí)，絕經(jīng)后HDL-C水平的下降被認(rèn)為會(huì)降低其心血管保護(hù)作用[28]。雖然維生素D與血脂異常間的關(guān)系尚未完全闡明，但有動(dòng)物研究報(bào)道，血清維生素D水平與HDL-C呈正相關(guān)，較低的維生素D與冠狀動(dòng)脈粥樣硬化的主要危險(xiǎn)因子相關(guān)[29]。本研究發(fā)現(xiàn)，絕經(jīng)后女性血清25-(OH)VD與TG呈負(fù)相關(guān)，與HDL-C呈正相關(guān)，提示維生素D缺乏可能在絕經(jīng)后人群相關(guān)代謝異常以及CVD發(fā)病過(guò)程中起重要作用。

有研究發(fā)現(xiàn)，血壓控制水平與血清25-(OH)VD水平有關(guān)[30-32]。但本研究未發(fā)現(xiàn)血壓水平與25-(OH)VD相關(guān)，可能由于本研究患者均為城市中離退休高級(jí)干部，良好的醫(yī)療保健水平使得其血壓受到了較好的控制。

絕經(jīng)被認(rèn)為會(huì)增加中心性肥胖[27]，同時(shí)，絕經(jīng)后女性BMI、腰圍也較絕經(jīng)前明顯增加[33]。歐美有研究發(fā)現(xiàn)，血清維生素D水平與體脂百分比、BMI、腰圍等指標(biāo)呈負(fù)相關(guān)[34-35]，維生素D增加了肥胖的發(fā)病風(fēng)險(xiǎn)[36]。本研究尚未發(fā)現(xiàn)BMI與25-(OH)VD相關(guān)，與韓國(guó)研究結(jié)論相似[10]?？紤]其可能與亞洲人體型較小、BMI波動(dòng)區(qū)間較小有關(guān)。

老年人皮膚維生素D產(chǎn)生減少[37]，因此常認(rèn)為維生素D的減少與年齡相關(guān)。但是，本研究中并未發(fā)現(xiàn)血清25-(OH)VD水平與年齡相關(guān)。這一現(xiàn)象可能與年齡相關(guān)的腎功能降低有關(guān)。動(dòng)物研究表明，隨著鼠齡增加引起腎功能的下降，其代謝清除25-(OH)VD的能力也隨之下降[38]。因此，隨著年齡增加皮膚產(chǎn)生的維生素D減少，但同時(shí)腎臟對(duì)于25-(OH)VD的利用也減少；這些效應(yīng)相互抵消，導(dǎo)致血清25-(OH)VD并未受到年齡的顯著影響。

維生素D缺乏已成為全球性問(wèn)題，并且日益嚴(yán)重[39]。當(dāng)體內(nèi)維生素D不足時(shí)，不僅會(huì)引起骨密度下降、骨折發(fā)生率明顯增加[40]，而且可導(dǎo)致微生物感染、代謝性疾病和CVD的發(fā)病率和病死率明顯升高[41-42]。國(guó)內(nèi)研究發(fā)現(xiàn)，我國(guó)老年人維生素D整體水平減低，維生素D缺乏者約占69.2%[8]。本研究發(fā)現(xiàn)，絕經(jīng)后女性維生素D缺乏率為78.7%，明顯高于我國(guó)普通老年人；在絕經(jīng)后MS患者中，維生素D缺乏率甚至高達(dá)87.3%。VD缺乏普遍存在于老年女性患者中，考慮可能與其戶外活動(dòng)較少、受太陽(yáng)照射時(shí)間減少、肝腎功能生理性減退及消化道對(duì)于營(yíng)養(yǎng)吸收較差有關(guān)。此外，隨年齡增加使肥胖者脂溶性維生素D分布容積增加，生物活性下降，也導(dǎo)致維生素D水平下降。提示對(duì)于絕經(jīng)后女性特別是合并MS者，適當(dāng)增加陽(yáng)光照射或者補(bǔ)充維生素D類似物有益健康。

綜上所述，本研究表明在絕經(jīng)后女性中，血清25-(OH)VD與MS具有一定相關(guān)性，提示維生素D缺乏可能在絕經(jīng)后人群相關(guān)代謝異常以及CVD發(fā)病過(guò)程中起重要作用。這為指導(dǎo)絕經(jīng)后女性合理補(bǔ)充維生素D提供依據(jù)與參考。本研究樣本量較少，其結(jié)論需要擴(kuò)大樣本量的重復(fù)研究來(lái)進(jìn)一步證實(shí)。

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(本文編輯：李婷婷)

Changes of Serum 25-hydrocyvitamin D Level in Elderly Women With Metabolic Syndrome and Its Clinical Significance

CHULin，SUNFang，LIUJie,etal.

DepartmentofGeriatrics,PekingUniversityPeople′sHospital,Beijing100044,China

Objective To investigate the relationship between serum 25-hydrocyvitamin D〔25-(OH)VD〕evel and occurrence of metabolic syndrome(MS) in elderly women.Methods 188 elderly post-menopausal female patients(60-94 years old) who were admitted to the department of geriatrics of Peking University People′s Hospital from September 2011 to November 2013,were selected as study subjects.79 cases with MS were included in MS group,109 without MS were included in non-MS group.According to the median serum 25-(OH)VD level(31.5 nmol/L),94 cases were included in <31.5 nmol/L group,94 cases were included in ≥31.5 nmol/L group.Blood pressure,body weight,body height,body mass index(BMI) were measured and calculated.Serum levels of fasting plasma glucose(FPG),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),glycosylated hemoglobin(HbA1c),serum fasting insulin(FINS)，calcium(Ca),phosphorus(P),25-(OH)VD，bone-specific alkaline phosphatase(BAP) and tartaric-resistant phosphatase(TRAP) were measured.The degree of 25-(OH)VD deficiency was compared between MS group and non-MS group,the correlation between serum level of 25-(OH)VD and observation indicators was analyzed.Results There were significant differences in duration of hypertension and diabetes,levels of TG,HDL-C,FPG,HbA1c,FINS and HOMA-IR between MS group and non-MS group(P<0.05).Serum level of 25-(OH)VD in MS group was significantly lower than that in non-MS group(P<0.05).There were significant differences in duration of hyperlipidemia,levels of TG,HDL-C,FPG,HbA1c,FINS and HOMA-IR between <31.5 nmol/L group and ≥31.5 nmol/L group(P<0.05).Serum level of 25-(OH)VD in ≥31.5 nmol/L group was significantly higher than that in <31.5 nmol/L group(P<0.05).There was significant difference in degree of 25-(OH)VD deficiency between MS group and non-MS group(P<0.05).Serum level of 25-(OH)VD was negatively correlated with level of TG,FPG and HOMA-IR,respectively,but was positively correlated with level of HDL-C(P<0.05).Conclusion Serum level of 25-(OH)VD is relatively low in elderly women and is related to levels of blood lipid and FPG.

Metabolic syndrome X；Elderly women；Vitamin D

100044 北京市，北京大學(xué)人民醫(yī)院老年科

劉杰，100044 北京市，北京大學(xué)人民醫(yī)院老年科；E-mail:doctortruly@163.com

R 589

A

10.3969/j.issn.1007-9572.2015.12.006

2014-07-21；

2014-11-21)