尉耘翠，祝茸，夏麗莉，劉芬，何燕

(首都醫(yī)科大學(xué)公共衛(wèi)生學(xué)院，北京100069)

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超重及肥胖人群中不同胰島素抵抗計(jì)算指數(shù)準(zhǔn)確性評(píng)價(jià)

尉耘翠，祝茸，夏麗莉，劉芬，何燕

(首都醫(yī)科大學(xué)公共衛(wèi)生學(xué)院，北京100069)

摘要：目的觀察不同胰島素抵抗(IR)計(jì)算指數(shù)評(píng)價(jià)超重及肥胖人群中IR的準(zhǔn)確性，尋找超重及肥胖人群更為理想的判定臨界值。方法研究對(duì)象為406例超重及肥胖的非糖尿病患者，計(jì)算納入者的穩(wěn)態(tài)模型胰島素抵抗指數(shù)(HOMA-IR)、定量胰島素敏感性檢測(cè)指數(shù)(QUICKI)、McAuley指數(shù)(McA)，以空腹胰島素≥12 mIU/L為IR金標(biāo)準(zhǔn)，評(píng)價(jià)各指數(shù)判定IR的準(zhǔn)確性。結(jié)果 406例超重及肥胖者中，IR 114例、非IR 292例。以HOMA-IR≥2.6判定IR時(shí)，IR 138例、非IR 268例，其靈敏度為94.74%、特異度為89.73%，約登指數(shù)為0.84；以HOMA-IR≥2.68作為判定切點(diǎn)時(shí)，其靈敏度為93.3%、特異度為92.9%，約登指數(shù)為0.86。以QUICKI≤0.339判定IR時(shí)，IR 210例、非IR196例，其靈敏度為100%、特異度為67.12%，約登指數(shù)為0.67；以QUICKI≤0.335作為判定切點(diǎn)時(shí)，其靈敏度為79.8%、特異度為99.0%，約登指數(shù)為0.79。以McA≤5.8判定IR時(shí)，IR 403例、非IR3例，其靈敏度為98.25%、特異度為0.34%，約登指數(shù)為-1.41；以McA≤4.29作為判定切點(diǎn)時(shí)，其靈敏度為78.0%、特異度為82.9%，約登指數(shù)為0.61。 結(jié)論在超重及肥胖人群中HOMA-IR能更準(zhǔn)確地評(píng)估IR；在這部分人群中判定IR時(shí)應(yīng)考慮肥胖及脂代謝對(duì)胰島素水平的影響作用，適當(dāng)調(diào)整判定臨界值，以便能提高評(píng)價(jià)IR的準(zhǔn)確性。

關(guān)鍵詞：超重；肥胖；胰島素抵抗；胰島素抵抗指數(shù)；穩(wěn)態(tài)模型胰島素抵抗指數(shù)；定量胰島素敏感性檢測(cè)指數(shù)；McAuley指數(shù)

北京市自然科學(xué)基金資助項(xiàng)目(713202)。

近年肥胖的發(fā)生率逐年上升[1]。研究發(fā)現(xiàn)，其與胰島素抵抗(IR)有關(guān)[2]。目前，IR的判定金標(biāo)準(zhǔn)為高胰島素正葡萄糖鉗夾技術(shù)[3]，但此法操作復(fù)雜，臨床普及困難。目前，大量研究采用空腹胰島素(FINS)≥12 mIU/L作為判定非糖尿病人群IR最為理想的指標(biāo)[4.5]。另外，學(xué)者還提出多項(xiàng)IR簡(jiǎn)易指數(shù)，如穩(wěn)態(tài)模型胰島素抵抗指數(shù)(HOMA-IR)[6]、定量胰島素敏感性檢測(cè)指數(shù)(QUICKI)[7]及McAuley指數(shù)(McA)[8]等。但是，以上指標(biāo)評(píng)價(jià)多基于全人群基礎(chǔ)，超重及肥胖人群仍缺乏準(zhǔn)確的IR效能評(píng)價(jià)標(biāo)準(zhǔn)。2014年5月～2015年8月，我們分析了HOMA-IR、QUICKI、McA評(píng)估超重及肥胖人群IR的靈敏度及特異度，旨在尋找判定IR的理想臨界值，為臨床早期預(yù)防IR提供依據(jù)?，F(xiàn)報(bào)告如下。

1資料與方法

1.1臨床資料納入標(biāo)準(zhǔn)：年齡≥20歲，BMI≥24 kg/m2，自愿參加，未口服影響糖、脂代謝藥物，近3個(gè)月內(nèi)未進(jìn)行任何節(jié)食或減肥者。排除標(biāo)準(zhǔn)：患有內(nèi)分泌疾病、肝腎疾病者。研究對(duì)象為406例超重及肥胖的非糖尿病患者，其中男252例、女154例，年齡20～67(43.97±10.28)歲；超重395例，肥胖11例； BMI 24.00～30.86 kg/m2，腰圍/臀圍比0.70～1.01。

1.2HOMA-IR、QUICKI、McA判定IR的效能分析10 h過(guò)夜禁食后于次日清晨抽取靜脈血2 mL,采用葡萄糖氧化酶方法測(cè)定空腹血糖(FBG)，采用標(biāo)準(zhǔn)酶分光光度技術(shù)測(cè)定HDL-C、LDL-C、TC、TG，采用ELISA法測(cè)定FINS。根據(jù)上述結(jié)果計(jì)算HOMA-IR、 QUICKI、McA。計(jì)算公式：HOMA-IR= FINS×(FBG/22.5)；QUICKI= 1/(logFINS+logFBG)；McA=exp(2.63-0.28lnFINS-0.31lnTG)。當(dāng)HOMA-IR≥2.6、QUICKI≤0.339、McA≤5.8被認(rèn)定為IR。以FINS≥12 μU/L值為金標(biāo)準(zhǔn)[4,5]評(píng)價(jià)HOMA-IR、 QUICKI、McA指數(shù)判定IR的靈敏度及特異度。

1.3統(tǒng)計(jì)學(xué)方法采用SPSS17.0統(tǒng)計(jì)軟件。采用ROC曲線分析法判定診斷界限值。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2結(jié)果

以FINS≥12 μU/L值為金標(biāo)準(zhǔn)，406例超重及肥胖者中IR 114例、非IR 292例。以HOMA-IR≥2.6判定IR時(shí)，IR 138例、非IR 268例；其靈敏度為94.74%、特異度為89.73%，約登指數(shù)為0.84，ROC曲線下面積(AUC)為0.98(95%CI：0.97～0.99,P≤0.001)。當(dāng)以HOMA-IR≥2.68作為判定切點(diǎn)時(shí)，其靈敏度為93.3%、特異度為92.9%，約登指數(shù)為0.86。以QUICKI≤0.339判定IR時(shí)，IR 210例、非IR196例；其靈敏度為100%、特異度為67.12%，約登指數(shù)為0.67,AUC為0.96(95%CI：0.95～0.98,P<0.01)。當(dāng)以QUICKI≤0.335作為判定切點(diǎn)時(shí)，其靈敏度為79.8%、特異度為99.0%，約登指數(shù)為0.79。以McA≤5.8判定IR時(shí)，IR 403例、非IR3例；其靈敏度為98.25%、特異度為0.34%，約登指數(shù)為-1.41；AUC為0.96(95%CI：0.95～0.98，P<0.01)。當(dāng)以McA≤4.29作為判定切點(diǎn)時(shí)，其靈敏度為78.0%、特異度為82.9%，約登指數(shù)為0.61。

3討論

大量研究表明，肥胖、高血壓、糖尿病等與IR相關(guān)的多種疾病均與FINS水平密切相關(guān)[9]。在非糖尿病人群中，F(xiàn)INS與高胰島素正糖鉗夾技術(shù)測(cè)定的葡萄糖代謝率相關(guān)性較好，可用以準(zhǔn)確預(yù)測(cè)機(jī)體IR的程度[4]。權(quán)威研究將FINS作為最簡(jiǎn)單有效的IR指標(biāo)，但糖尿病患者FINS與金標(biāo)準(zhǔn)相關(guān)性較差。其主要原因是FINS水平由胰島素分泌和胰島素敏感性二者共同決定，而糖尿病患者即使已呈顯著IR狀態(tài)，但會(huì)由于胰島素分泌缺陷而使胰島素水平不高。因此，糖尿病人群不宜采用FINS作為IR判定標(biāo)準(zhǔn)。以往研究發(fā)現(xiàn)，F(xiàn)INS水平與BMI及TG水平均存在顯著正相關(guān)?，F(xiàn)有研究表明，這種相關(guān)性不僅與BMI相關(guān)，還在很大程度上與脂肪分布情況相關(guān)。因此，向心性肥胖的患者更容易患代謝綜合征[10]。成年人降低體質(zhì)量可降低胰島素水平，增加胰島素敏感性，提示減輕體質(zhì)量對(duì)防止IR的發(fā)生具有一定作用[11]。目前,幾種IR計(jì)算指標(biāo)的標(biāo)準(zhǔn)設(shè)定均基于全人群基礎(chǔ)，未考慮脂代謝的作用。因此,超重及肥胖人群IR臨界值的選擇應(yīng)更為保守。

HOMA-IR是另一種被廣泛使用的IR指標(biāo)。既往研究[12，13]在大樣本中驗(yàn)證了HOMA-IR與胰島素鉗夾技術(shù)測(cè)定結(jié)果具有較好相關(guān)性，可較好地用于臨床和流行病學(xué)調(diào)查[14]。目前，國(guó)內(nèi)多項(xiàng)IR相關(guān)研究以所研究人群HOMA-IR 的P75值作為IR判定界值，發(fā)現(xiàn)其臨界變化很大，也有研究認(rèn)為其參考值應(yīng)因性別、年齡而異[15]。國(guó)外研究常以HOMA-IR≥2.6或近似值作為IR的參考值，變化范圍較小。本研究發(fā)現(xiàn)，相對(duì)于QUICKI及McA指數(shù)，HOMA-IR判定IR的準(zhǔn)確性更好。多項(xiàng)研究顯示，HOMA-IR在檢驗(yàn)IR程度具有較高的靈敏度和特異度，且比QUICKI更為可靠[16]。Conwell等[17]也報(bào)道了相似結(jié)果，不同時(shí)點(diǎn)的HOMA-IR與胰島素敏感性呈現(xiàn)顯著負(fù)相關(guān)。兒童及青少年人群中FINS、HOMA-IR、QUICKI與靜脈葡萄糖耐量實(shí)驗(yàn)結(jié)果也具有強(qiáng)相關(guān)性。本研究發(fā)現(xiàn)，超重及肥胖人群中HOMA-IR判定IR準(zhǔn)確定最好，而當(dāng)HOMA-IR≥2.68時(shí)其判定IR的準(zhǔn)確性最佳。

前期研究表明，QUICKI在不同時(shí)間點(diǎn)與敏感性呈顯著正相關(guān)[17]。本研究中以常用標(biāo)準(zhǔn)QUICKI≤0.339來(lái)判定IR時(shí)特異度較低。進(jìn)一步分析我們發(fā)現(xiàn)，在超重及肥胖人群中以QUICKI≤0.335作為IR判定切點(diǎn)為時(shí)，其準(zhǔn)確性最好。因此，超重及肥胖人群判定IR時(shí)應(yīng)考慮降低臨界值。而McA指數(shù)也是檢驗(yàn)IR較為準(zhǔn)確的間接指標(biāo)，尤其是在葡萄糖代謝最小估計(jì)模型下其靈敏度和特異度都很高[8,18]。以目前常用標(biāo)準(zhǔn)McA≤5.8判定超重及肥胖人群IR時(shí)，特異度僅為0.34%，提示在中國(guó)超重及肥胖人群中此IR判定界值偏高，特異度較低，應(yīng)合理下調(diào)判定切點(diǎn)。我們發(fā)現(xiàn)在超重及肥胖人群中，當(dāng)以McA≤4.29作為判定切點(diǎn)時(shí)其判定IR準(zhǔn)確性最好，能更可靠地判定IR人群，有助于開(kāi)展代謝性疾病的早期預(yù)防。

綜上所述，超重及肥胖人群中HOMA-IR具有更好的IR判定準(zhǔn)確性，在這部分人群中判定IR時(shí)應(yīng)考慮肥胖及脂代謝對(duì)胰島素水平的影響作用，適當(dāng)調(diào)整判定臨界值，以便為IR的早發(fā)現(xiàn)、早預(yù)防提供準(zhǔn)確依據(jù)。

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Evaluation of different indices of insulin resistance in overweight and

obese population

YUYun-cui,ZHURong,XIALi-li,LIUFen,HEYan

(CapitalMedicalUniversity,Beijing100069,China)

Abstract:ObjectiveTo observe the accuracy of several indices in assessing insulin resistance (IR) in the overweight/obesity population and to find more desirable cut-off point of IR. Methods This study involved 406 overweight/obesity participants without overt diabetes. Homeostasis model assessment of insulin resistance (HOMA-IR) index, Quantitative insulin sensitivity check index (QUICKI) and McAuley index (McA index) were calculated and compared with fasting insulin levels (FINS) (≥12 mIU/L, which was the reference criteria for determined IR). ResultsOf the 406 participants, 114 cases of IR and 292 cases of non-IR were found. When using HOMA-IR≥2.6 as the cut-off point of IR, there were 138 cases of IR and 268 cases of non-IR. The sensitivity was 94.74% and the specificity was 89.73%. Youden index was 0.84. When using HOMA-IR≥2.68 as the cut-off point, the sensitivity and specificity was 93.3% and 92.9%, respectively. Youden index was elevated to 0.86. When using QUICKI≤0.339 as the cut-off point of IR, there were 210 cases of IR and 196 cases of non-IR. The sensitivity was 100% and the specificity was 67.12%. Youden index was 0.67. When using QUICKI≤0.335 as the cut-off point, the sensitivity and specificity was 79.8% and 99.0%, respectively. Youden index was increased to 0.79. When using McA≤5.8 as the cut-off point of IR, there were 403 cases of IR and 3 cases of non-IR. The sensitivity was 98.25% and the specificity was only 0.34%. Youden index was -1.41. When using McA≤4.29 as the cut-off point, the sensitivity and specificity was 78.0% and 82.9%, respectively. Youden index was increased to 0.61. ConclusionsHOMA-IR is more accurate in detecting IR in overweight/obese population. The thresholds of these three indices in overweight/obese population should be adjusted appropriately considering the influence of obesity and lipid metabolism on insulin levels to increase the accuracy in evaluating IR.

Key words:overweight; obesity; insulin resistance; insulin resistance index; homeostasis model assessment of insulin resistance index; quantitative insulin sensitivity check index; McAuley index

收稿日期：(2015-09-10)

通信作者簡(jiǎn)介：何燕(1962-)，女，博士，教授，博士生導(dǎo)師，主要研究方向?yàn)槁圆×餍胁W(xué)。E-mail： yanhe1220@126.com

作者簡(jiǎn)介：第一尉耘翠(1990-)，女，碩士研究生在讀，主要研究方向?yàn)槁圆×餍胁W(xué)。E-mail： yuyuncui7@126.com

基金項(xiàng)目：國(guó)家自然科學(xué)基金資助項(xiàng)目(30971178, 30670778)；“十二五”國(guó)家科技支撐計(jì)劃重點(diǎn)資助項(xiàng)目(2015BAI09B01)；

中圖分類號(hào)：R181.3

文獻(xiàn)標(biāo)志碼：A

文章編號(hào)：1002-266X(2015)46-0014-03

doi：10.3969/j.issn.1002-266X.2015.46.005