樊金夢(mèng),齊昊
摘要 綜述三酰甘油-葡萄糖(TyG)指數(shù)與2型糖尿病(T2DM)及其并發(fā)癥的關(guān)系。胰島素抵抗(IR)是T2DM的主要發(fā)病機(jī)制,早期識(shí)別IR對(duì)于預(yù)測(cè)及預(yù)防T2DM的發(fā)病、延緩疾病進(jìn)展具有重要意義。TyG指數(shù)可作為IR的替代指標(biāo),且其與T2DM及其并發(fā)癥存在不同程度的關(guān)系。
關(guān)鍵詞2型糖尿病并發(fā)癥;三酰甘油-葡萄糖指數(shù);胰島素抵抗;2型糖尿??;綜述
doi:10.12102/j.issn.1672-1349.2024.04.017
2021年國際糖尿病聯(lián)盟組織發(fā)布的全球糖尿病最新數(shù)據(jù)顯示,全球20~79歲糖尿病病人5.37億例,其中,我國糖尿病病人1.4億例,居世界首位[1]。糖尿病已成為威脅我國的公共衛(wèi)生問題,盡早發(fā)現(xiàn)糖尿病及其并發(fā)癥的高危人群并予以干預(yù),對(duì)于減輕社會(huì)醫(yī)療負(fù)擔(dān)具有重要意義。胰島素抵抗(insulin resistance,IR)在2型糖尿?。╰ype 2 diabetes mellitus,T2DM)的發(fā)病機(jī)制中具有重要作用。三酰甘油-葡萄糖(triglyceride-glucose,TyG)指數(shù)可作為IR的替代指標(biāo)。本研究就TyG指數(shù)與T2DM及其并發(fā)癥的關(guān)系進(jìn)行綜述。
1IR與TyG指數(shù)
高胰島素-正葡萄糖鉗夾試驗(yàn)是測(cè)定IR的金標(biāo)準(zhǔn),但其費(fèi)用昂貴、操作復(fù)雜,臨床適用性有限[2]。近年來,研究者陸續(xù)提出各種方法評(píng)估IR,其中胰島素抵抗的穩(wěn)態(tài)模型評(píng)估(homeostatic model assessmentofinsulin resistance,HOMA-IR)在臨床中的應(yīng)用最廣泛[3]。然而,HOMA-IR計(jì)算時(shí)需測(cè)定空腹胰島素水平,這在基層衛(wèi)生機(jī)構(gòu)難以實(shí)現(xiàn),并且HOMA-IR對(duì)糖尿病的預(yù)測(cè)受年齡影響較大[4]。內(nèi)臟脂肪指數(shù)(visceral adiposity index,VAI)、脂質(zhì)積累產(chǎn)物(lipid accumulation product,LAP)、TyG指數(shù)等IR評(píng)估指標(biāo)中,TyG指數(shù)的評(píng)估效能明顯優(yōu)于HOMA-IR,且檢測(cè)成本低、獲取方便,在臨床實(shí)用性更強(qiáng)[5-6]。
2TyG指數(shù)與T2DM
盡管關(guān)于T2DM的發(fā)病機(jī)制尚未明確,但普遍認(rèn)為是遺傳因素、環(huán)境因素、生活方式及行為因素共同作用的結(jié)果,其中,IR與β細(xì)胞功能下降是T2DM發(fā)病的重要過程。機(jī)體三酰甘油過多使脂肪組織存儲(chǔ)脂肪酸減少,循環(huán)中游離脂肪酸增多,積聚在肌肉、肝臟、胰島β細(xì)胞等胰島素敏感的非脂肪組織中,形成異位脂質(zhì)沉積,引起相應(yīng)組織細(xì)胞損傷,即脂毒性。過量的脂肪酸產(chǎn)生有毒的酯化產(chǎn)物如二?;视秃蜕窠?jīng)酰胺,阻礙胰島素信號(hào)轉(zhuǎn)導(dǎo)通路,減少機(jī)體葡萄糖攝取并導(dǎo)致IR;過多的脂質(zhì)及其引起的脂毒性使胰島β細(xì)胞產(chǎn)生應(yīng)激反應(yīng),如線粒體功能障礙、內(nèi)質(zhì)網(wǎng)應(yīng)激和細(xì)胞自噬,這些應(yīng)激反應(yīng)又可導(dǎo)致胰島β細(xì)胞損傷及胰島素分泌減少[7]。同時(shí),機(jī)體長(zhǎng)期處于高糖環(huán)境時(shí),由于氧化應(yīng)激作用導(dǎo)致線粒體損傷,產(chǎn)生大量的氧自由基,影響胰島素基因的轉(zhuǎn)錄與表達(dá),使胰島β細(xì)胞功能受損,促進(jìn)其凋亡,進(jìn)而導(dǎo)致IR及胰島素分泌減少[8]。
2.1TyG指數(shù)預(yù)測(cè)T2DM發(fā)病風(fēng)險(xiǎn)
目前,已有多項(xiàng)研究證實(shí)TyG指數(shù)與T2DM發(fā)病風(fēng)險(xiǎn)存在相關(guān)性。研究顯示,TyG指數(shù)預(yù)測(cè)T2DM的發(fā)生優(yōu)于HOMA-IR[6]。Zou等[9]研究顯示,在內(nèi)臟脂肪肥胖和(或)異位脂肪肥胖、體質(zhì)指數(shù)(BMI)<25 kg/m2的人群中,TyG指數(shù)與T2DM發(fā)病獨(dú)立相關(guān),而在BMI值超標(biāo)時(shí)這種關(guān)系不再呈正相關(guān)。Zhang等[10]進(jìn)行的前瞻性隊(duì)列研究發(fā)現(xiàn),TyG指數(shù)對(duì)于體重正常人群T2DM的發(fā)生也有預(yù)測(cè)價(jià)值。Yoon等[5]對(duì)超重或肥胖兒童與青少年的研究顯示,TyG指數(shù)與IR顯著相關(guān),且其預(yù)測(cè)價(jià)值優(yōu)于HOMA-IR。然而,TyG指數(shù)與T2DM發(fā)病風(fēng)險(xiǎn)的關(guān)系目前尚無定論,有研究顯示二者之間呈線性相關(guān)[11],而Pranata等[12]研究發(fā)現(xiàn),TyG指數(shù)>8.6時(shí),TyG指數(shù)與T2DM發(fā)病的劑量-反應(yīng)曲線變得更陡峭。Xuan等[13]研究指出,TyG指數(shù)與T2DM的發(fā)病風(fēng)險(xiǎn)為U型相關(guān),TyG指數(shù)在閾值內(nèi)(男性為7.97,女性為7.27)時(shí)T2DM發(fā)病風(fēng)險(xiǎn)最低,高于閾值時(shí)二者呈正相關(guān),反之呈負(fù)相關(guān);我國的一項(xiàng)研究也發(fā)現(xiàn)了這種U型相關(guān)關(guān)系,但閾值(8.51)有差異[14]。
2.2TyG指數(shù)與T2DM診斷
目前,口服葡萄糖耐量試驗(yàn)是診斷糖尿病的金標(biāo)準(zhǔn),但其抽血次數(shù)多,病人依從性差,因此,迫切需要探索可替代口服葡萄糖耐量試驗(yàn)的易獲得的臨床指標(biāo)[15]。美國糖尿病協(xié)會(huì)推薦將糖化血紅蛋白作為診斷糖尿病前期或糖尿病的指標(biāo),且已有研究證實(shí)糖化血紅蛋白預(yù)測(cè)糖尿病或糖尿病前期的效能[16]。一項(xiàng)對(duì)TyG指數(shù)、VAI、LAP鑒別糖尿病前期或糖尿病準(zhǔn)確性的研究發(fā)現(xiàn),與VAI及LAP相比,TyG指數(shù)的曲線下面積(AUC)較大,男性閾值為8.75,女性閾值為8.53,此結(jié)果表明TyG指數(shù)診斷糖尿病前期或糖尿病的效能與糖化血紅蛋白一致性較高,且該研究發(fā)現(xiàn)TyG指數(shù)的閾值最穩(wěn)定,不隨年齡波動(dòng)[17]。因此,TyG指數(shù)可作為早期診斷糖尿病前期及糖尿病的精確簡(jiǎn)便的指標(biāo)。然而,國內(nèi)尚缺乏相關(guān)研究,因此其是否適用于我國人群尚有待研究。
2.3TyG指數(shù)與T2DM血糖控制
糖化血紅蛋白是臨床公認(rèn)的評(píng)估血糖控制的標(biāo)志,可反映近2~3個(gè)月血糖控制水平,但糖化血紅蛋白檢測(cè)價(jià)格較高、實(shí)驗(yàn)室質(zhì)控差異往往會(huì)導(dǎo)致測(cè)量誤差[18]。Hameed[19]研究發(fā)現(xiàn),TyG指數(shù)與糖化血紅蛋白及IR獨(dú)立相關(guān),此與Selvi等[20]的研究結(jié)果一致,且AUC面積均>0.8,表明TyG指數(shù)同樣可用于評(píng)估血糖控制的情況。
3TyG指數(shù)與T2DM并發(fā)癥
3.1TyG指數(shù)與T2DM心血管病變
心血管疾病的發(fā)生是全球疾病死亡率升高的重要原因,T2DM及IR是引起心血管事件的重要因素[21]。早期風(fēng)險(xiǎn)檢測(cè)對(duì)預(yù)防心血管事件具有重要意義。Si等[22]對(duì)T2DM合并或不合并冠心病人群的研究發(fā)現(xiàn),TyG指數(shù)是T2DM合并冠心病的獨(dú)立危險(xiǎn)因素。Tai等[23]對(duì)我國T2DM病人平均隨訪7.7年發(fā)現(xiàn),在傳統(tǒng)心血管風(fēng)險(xiǎn)因素調(diào)整后,TyG指數(shù)與T2DM病人發(fā)生心血管事件顯著相關(guān),且TyG指數(shù)每升高1個(gè)標(biāo)準(zhǔn)差,病人主要不良心血管事件(major adverse cardiovascular events,MACEs)的風(fēng)險(xiǎn)增加19.00%。2021年一項(xiàng)橫斷面研究提出TyG指數(shù)升高是冠狀動(dòng)脈狹窄的高危因素,且與冠狀動(dòng)脈狹窄的數(shù)量及嚴(yán)重程度相關(guān)[24]。此外,多項(xiàng)研究也表明TyG指數(shù)與T2DM病人行經(jīng)皮冠狀動(dòng)脈介入治療(PCI)術(shù)或冠狀動(dòng)脈搭橋術(shù)的預(yù)后顯著相關(guān),TyG指數(shù)越高,發(fā)生MACEs的風(fēng)險(xiǎn)越大[25-26]。因此,TyG指數(shù)可作為T2DM病人發(fā)生心血管事件的預(yù)測(cè)指標(biāo)。
3.2TyG指數(shù)與T2DM足潰瘍
足潰瘍是T2DM常見的嚴(yán)重并發(fā)癥,具有高致殘率、高致死率的特點(diǎn)[15]。目前,對(duì)于T2DM足潰瘍尚無有效的治療方法,因此早期篩查及預(yù)防十分重要。研究發(fā)現(xiàn),IR與T2DM足潰瘍的起病及嚴(yán)重程度相關(guān)[27]。李航等[28]研究了作為IR替代指標(biāo)的TyG指數(shù)對(duì)T2DM足潰瘍的影響,發(fā)現(xiàn)TyG指數(shù)是T2DM足潰瘍的影響因素,其預(yù)測(cè)T2DM足潰瘍的AUC為0.680~0.742。目前,國內(nèi)外關(guān)于TyG指數(shù)與T2DM足潰瘍關(guān)系的研究較少,需進(jìn)一步研究證實(shí)。
3.3TyG指數(shù)與T2DM腎病
糖尿病腎?。╠iabetic kidney disease,DKD)是糖尿病常見的微血管并發(fā)癥之一,我國T2DM中DKD的患病率已達(dá)21.8%[29]。IR與T2DM病人發(fā)生DKD有關(guān),嚴(yán)重的IR會(huì)導(dǎo)致T2DM病人出現(xiàn)微量白蛋白尿和估算腎小球?yàn)V過率(estimated glomerular filtration rate,eGFR)下降[30]。TyG指數(shù)作為IR的替代指標(biāo),與DKD相關(guān)。Lv等[31]研究發(fā)現(xiàn),高TyG指數(shù)的病人出現(xiàn)微量白蛋白尿及eGFR<60 mL/(min·1.73 m2)的比例更高,且發(fā)生DKD的風(fēng)險(xiǎn)也更高。Liu等[32]進(jìn)行的橫斷面研究表明,TyG指數(shù)預(yù)測(cè)DKD發(fā)病風(fēng)險(xiǎn)的最佳閾值為9.66,高于此值時(shí)發(fā)病風(fēng)險(xiǎn)顯著升高。同樣,Shang等[33]通過納入950例經(jīng)活檢確診DKD的病人進(jìn)行研究,發(fā)現(xiàn)TyG指數(shù)預(yù)測(cè)DKD發(fā)病風(fēng)險(xiǎn)的潛在閾值為9.05~9.09,當(dāng)T2DM病人TyG指數(shù)高于此閾值時(shí),可將其歸為DKD的高危人群,盡早進(jìn)行預(yù)防。
3.4TyG指數(shù)與T2DM視網(wǎng)膜病變
糖尿病視網(wǎng)膜病變(diabetic retinopathy,DR)也是糖尿病的一種常見并發(fā)癥,研究表明,血清三酰甘油控制不佳與增生性視網(wǎng)膜病變進(jìn)展相關(guān)[34];在調(diào)整了年齡、性別、血壓等影響因素后,TyG指數(shù)與DR獨(dú)立相關(guān)[35]。Yao等[36]進(jìn)行的一項(xiàng)巢式病例對(duì)照研究結(jié)果顯示,TyG指數(shù)與不同嚴(yán)重程度的DR均顯著相關(guān)。然而,Pan等[37]的研究卻未發(fā)現(xiàn)上述相關(guān)性。目前,關(guān)于TyG指數(shù)與糖尿病視網(wǎng)膜病變關(guān)系的研究較少,且不同種族人群間存在差異,因此需更多的研究判斷二者的相關(guān)性。
3.5TyG指數(shù)與T2DM神經(jīng)病變
糖尿病神經(jīng)病變發(fā)病機(jī)制尚不明確,可能與氧化應(yīng)激、微循環(huán)障礙、IR、神經(jīng)營(yíng)養(yǎng)因子缺乏等有關(guān)[38-39]。研究表明,胰島素具有營(yíng)養(yǎng)神經(jīng)的作用,胰島素缺乏是糖尿病神經(jīng)病變的主要原因[40]。目前,有研究建議將TyG指數(shù)作為IR替代指標(biāo)預(yù)測(cè)糖尿病神經(jīng)病變[41-42]。Akbar等[41]研究發(fā)現(xiàn),有心臟自主神經(jīng)病變病人的TyG指數(shù)較高,因此TyG指數(shù)可能是早期篩查糖尿病神經(jīng)病變高危病人的指標(biāo)。田福璐[42]通過多因素分析發(fā)現(xiàn),TyG指數(shù)與糖尿病神經(jīng)病變顯著相關(guān)(OR值為8.641,AUC為0.773)。但以上研究均屬于橫斷面研究,無法明確TyG指數(shù)與2型糖尿病神經(jīng)病變之間的因果關(guān)系,尚需進(jìn)一步的隊(duì)列研究確定。
4小結(jié)與展望
TyG指數(shù)綜合了空腹血糖及三酰甘油的代謝狀況,其檢測(cè)方便、經(jīng)濟(jì),病人依從性好,便于基層醫(yī)院實(shí)施,可作為IR的替代指標(biāo)用于臨床預(yù)測(cè)T2DM及其并發(fā)癥的進(jìn)展。TyG指數(shù)的發(fā)現(xiàn)與應(yīng)用有利于減輕T2DM病人的就醫(yī)負(fù)擔(dān),減輕國家及社會(huì)的醫(yī)療重?fù)?dān)。目前,缺乏針對(duì)不同種族、不同人群、不同性別的TyG指數(shù)的統(tǒng)一閾值,且臨床上將TyG指數(shù)作為干預(yù)指標(biāo)預(yù)防T2DM及其并發(fā)癥的發(fā)生或控制病程進(jìn)展的可靠性尚未可知,未來還需進(jìn)行大量的前瞻性隊(duì)列研究論證。
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(收稿日期:2022-11-11)
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