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一鑒二查三治療，新一代長(zhǎng)效胰島素有妙招,！ HbA1c以外的血糖維度究竟該如何精確度量,？科技發(fā)展使得動(dòng)態(tài)血糖監(jiān)測(cè),、掃描式葡萄糖監(jiān)測(cè)等血糖監(jiān)測(cè)手段愈加豐富，但血糖控制狀況評(píng)價(jià)指標(biāo)呼喚全面,、有效、簡(jiǎn)單,、直觀(guān)的統(tǒng)一標(biāo)準(zhǔn),。 TIR就是時(shí)下研究火熱的新標(biāo)準(zhǔn)。狹義的TIR是指24小時(shí)內(nèi)葡萄糖在目標(biāo)范圍內(nèi)（通常為3.9~10.0 mmol/L,，或?yàn)?.9~7.8 mmol/L）的時(shí)間（一般用min表示）或其所占的百分比[12],。在CGM報(bào)告中，TIR可以餅圖的形式直觀(guān)表示,。通常所說(shuō)的TIR為狹義的TIR,，而廣義的TIR可以指葡萄糖處于不同范圍內(nèi)（低值、高值）的時(shí)間[12,13],，臨床中亦應(yīng)對(duì)廣義的TIR進(jìn)行定量,。當(dāng)然，在臨床應(yīng)用中可以將TIR與其他血糖指標(biāo)結(jié)合起來(lái)綜合反映個(gè)體血糖全貌,。 一項(xiàng)納入18項(xiàng)隨機(jī)對(duì)照研究的系統(tǒng)性綜述顯示,，TIR和HbA1c之間存在線(xiàn)性關(guān)系[14]，TIR能更好的反映相同HbA1c時(shí)低血糖的發(fā)生狀況和血糖變異程度[15],。TIR與糖尿病并發(fā)癥的關(guān)系如何呢,？美國(guó)Jaeb健康研究中心Beck教授利用DCCT數(shù)據(jù)，分析TIR與糖尿病并發(fā)癥進(jìn)展的相關(guān)性,，以驗(yàn)證TIR是否可以作為臨床試驗(yàn)的結(jié)局指標(biāo),，結(jié)果發(fā)現(xiàn),，TIR越短，糖尿病患者微量白蛋白尿,、視網(wǎng)膜病變發(fā)生率越高[16],。中國(guó)首個(gè)TIR與糖尿病并發(fā)癥研究亦證實(shí)，TIR與糖尿病患者視網(wǎng)膜病變嚴(yán)重程度呈顯著負(fù)相關(guān)（圖1）[17],。另一項(xiàng)納入9028例糖尿病或非糖尿病的危重癥患者的回顧性研究表明,，TIR越短，糖尿病危重癥患者死亡風(fēng)險(xiǎn)越大[18],。 圖1 中國(guó)證據(jù)：TIR與糖尿病患者視網(wǎng)膜病變嚴(yán)重程度呈顯著負(fù)相關(guān) 2019年《TIR國(guó)際共識(shí)推薦》針對(duì)1型糖尿?。═1DM）/T2DM、老年或高風(fēng)險(xiǎn)T1DM/T2DM,、T1DM合并妊娠,、T2DM合并妊娠/妊娠糖尿病四類(lèi)人群，確定了個(gè)體化的TIR目標(biāo)值（圖2）[1],，為臨床實(shí)踐提供了依據(jù),。 圖2 TIR國(guó)際共識(shí)推薦推薦的個(gè)體化TIR目標(biāo)值 血糖管理已經(jīng)邁入新維度，我們有沒(méi)有辦法來(lái)積極應(yīng)對(duì),？ 新型長(zhǎng)效基礎(chǔ)胰島素類(lèi)似物德谷胰島素上市后,，已成為臨床醫(yī)生的得力助手。德谷胰島素在皮下能夠形成可溶性的多六聚體長(zhǎng)鏈,，這是其主要延長(zhǎng)作用機(jī)制,；血液中胰島素單體的緩慢釋放并與白蛋白結(jié)合是其次要延長(zhǎng)作用機(jī)制[19]。德谷胰島素半衰期約25小時(shí),，可實(shí)現(xiàn)24小時(shí)平穩(wěn)控糖（圖3）[20,21],。研究表明，在同樣給藥間隔的條件下,，半衰期長(zhǎng)的藥物波峰/波谷波動(dòng)更?。▓D4）。 圖3 德谷胰島素24小時(shí)平穩(wěn)控糖 圖4 同樣給藥間隔,，半衰期長(zhǎng)的藥物波峰/波谷波動(dòng)更小 研究證實(shí),，德谷胰島素不僅改善HbA1c、空腹血糖,，還能減少低血糖風(fēng)險(xiǎn),，減少胰島素劑量[22]。與甘精胰島素相比,，德谷胰島素降糖療效的日內(nèi)變異性和降糖療效的日間變異性更低[23],，其中降糖療效的日間變異性為甘精胰島素的1/4（圖5）[21]。一項(xiàng)多中心、隨機(jī)對(duì)照,、開(kāi)放標(biāo)簽的研究表明,，對(duì)于新起始胰島素治療的T2DM患者，德谷胰島素降糖療效的日間變異性較甘精胰島素更低[24],；另一項(xiàng)研究采取動(dòng)態(tài)血糖監(jiān)測(cè)系統(tǒng)（CGMS）評(píng)估轉(zhuǎn)換為德谷胰島素治療的血糖變異性,，結(jié)果由其他基礎(chǔ)胰島素轉(zhuǎn)換為德谷胰島素治療后，降糖療效的日內(nèi)變異性及降糖療效的日間變異性也均顯著降低[25],?？梢?jiàn)德谷胰島素是多維度優(yōu)化血糖管理的有效手段。 圖5 德谷胰島素降糖療效的日間變異性為甘精胰島素的1/4 血糖變異性,、低血糖和HbA1c互相關(guān)聯(lián),，共同影響糖尿病患者管理目標(biāo)?？萍及l(fā)展使得血糖控制的精確度量成為可能,，TIR作為新型的血糖評(píng)估指標(biāo)，可幫助改善糖尿病患者血糖管理,。而新型長(zhǎng)效基礎(chǔ)胰島素類(lèi)似物——德谷胰島素,，具有獨(dú)特的延長(zhǎng)作用機(jī)制，實(shí)現(xiàn)24小時(shí)平穩(wěn)控糖,。研究證實(shí),，德谷胰島素在有效降糖同時(shí)，血糖變異性更低,、低血糖風(fēng)險(xiǎn)更小,，可更好地助力多維度優(yōu)化血糖管理。 參考文獻(xiàn) [1]Battelino T, Danne T, Bergenstal RM, et al. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus>[2]Skyler J S. Diabetic complications. The importance of glucose control.[J]. Endocrinology & Metabolism Clinics of North America, 1996, 25(2):243-54. [3]Stratton IM, et al. Association of glycaemia with macrovas- cular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study[J]. BMJ, 2000, 321(7258):405-12. [4]Hirsch IB. Glycemic variability and diabetes complications: does it matter? Of course it does![J]. Diabetes Care, 2015, 38:1610-4. [5]Patel A, MaeMbaon S, Chalmers J, et al. The ADVANCE collaboartive gorup. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes[J]. N Engl J Med, 2008, 358: 2560-72. [6]Gerstein HC, Miller ME, Byington RP, et al. The action to control cardiovascular risk in diabetes study group. Effects of intensive glucose lowering in type 2 diabetes[J]. N Engl J Med, 2008, 358: 2545-2559. [7]Beck R W, Connor C G, Mullen D M, et al. The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading[J]. Diabetes Care, 2017, 40(8):994-999. [8]Lipska K J, Margaret W E, Huang E S, et al. HbA1cand Risk of Severe Hypoglycemia in Type 2 Diabetes[J]. Diabetes Care, 2013, 36(11):3535-3542. [9]Oskarsson P, Antuna R, Geelhoed-Duijvestijn P, et al. Impact of flash glucose monitoring>[10]Penckofer S, Quinn L, Byrn M, et al. Does glycemic variability impact mood and quality of life?[J]. Diabetes Technology & Therapeutics, 2012, 14(4):303-10. [11]Tang X, Li S, Wang Y, et al. Glycemic variability evaluated by continuous glucose monitoring system is associated with the 10-y cardiovascular risk of diabetic patients with well-controlled HbA1c[J]. Clinica Chimica Acta, 2016, 461:146-150. [12]戴冬君. 持續(xù)葡萄糖監(jiān)測(cè)新指標(biāo):葡萄糖在目標(biāo)范圍內(nèi)時(shí)間的臨床意義解析[J]. 中華糖尿病雜志, 2019, 11(2):139-142. [13]Danne T, Nimri R, Battelino T, et al. International Consensus>[14]Vigersky RA, et al. The Relationship of Hemoglobin A1C to Time-in-Range in Patients with Diabetes[J]. Diabetes Technol Ther, 2019, 21(2):81-85. [15]Vigersky RA, et al. Going beyond HbA1c to understand the benefits of advanced diabetes therapies[J]. J Diabetes, 2019, 11(1)23-31. [16]Beck RW, et al. Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials[j]. Diabetes Care, 2019, 42(3):400-405. [17]Lu J, et al. Association of Time in Range, as Assessed by Continuous Glucose Monitoring, With Diabetic Retinopathy in Type 2 Diabetes[J]. Diabetes Care. 2018, 41(11):2370-2376. [18]Lanspa MJ, et al. Chest. 2019 Jun. [19]Ib J, Svend H, Thomas H J, et al. Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin[J]. Pharmaceutical Research, 2012, 29(8):2104-2114. [20]Heise T, H?velmann U, Nosek L, et al. Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine[J]. Expert Opinion>[21]Heise T, Hermanski L, Nosek L, et al. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady‐state conditions in type 1 diabetes[J]. Diabetes Obesity & Metabolism, 2012, 14(9):859-864. [22]Evans M, Mcewan P, Foos V. Insulin degludec early clinical experience: does the promise from the clinical trials translate into clinical practice-a case-based evaluation[J]. J Med Econ, 2015, 18(2):96-105. [23]Heise Tim,，Kaplan Kadriye，Haahr Hanne L. Day-to-Day and Within-Day Variability in Glucose-Lowering Effect Between Insulin Degludec and Insulin Glargine (100 U/mL and 300 U/mL): A Comparison Across Studies[J]. J Diabetes Sci Technol, 2018, 12(2):356-363. [24]Aso Y, Suzuki K, Chiba Y, et al. Effect of insulin degludec versus insulin glargine>[25]Henao-Carrillo DC, et al. J Clin Transl Endocrinol. 2018 Mar 26;12:8-12 |
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