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WgÌIՓČWƽ_ǰλãWg > > šTʿՓ > ͬȌWTʿՓ > RtWTʿՓ

נټغIKpP“о

rg2020-02-10 ԴtƴW ߣ ֔10161
ժҪ
 

Ŀģ


1̽ӑ 2 T2DM߁RלpSCHcIKDKDP2̽ӑנٹ T2DM ߼נټc DKDIKpָ˵P

נټغIKpP“о
 



Part


ռ 2017.09-2018.08 tƴWxtԺIסԺķϗl 656 T2DM MЙMоټנټأTSH≤4.2mIU/lTSH4.2mIU/l ֞M SCH MM TSH Ƿ2.5mIU/l ֵ֞MֵM^MRYIСIСܓpָIKСָԼ DKD ʵIJؚwͬˮƽ TSH DKD P׵ΣUSCH cIΣU֌ӵP TSH Bm׃ TSH cIKpָ˵P

Part

һо 74 SCH ų{ļנٹ582T2DM MЙMоǷϲDKD ֞oDKDMDKDM^ɽM߻RYԼנٹܜyԇYIJؚwxԭᣨFT3xנأFT4ķλc DKD׵P FT3FT4 һBm׃cIKpָ˵P

Y

Part


1о 656 סԺ T2DM SCH Ļʞ 10.3ŮԻ SCH Ļʣ16.1%@Իߣ8.4%Mgոo}Ѫ{ѪǣFPGǻѪtףHbAlcTGđ̴TCܶ֬đ̴LDL-C揈DBPףTPȱDøALTȲDøASTᣨUAᵪBUNָѪHBPʲoyӋWxc TSH2.5 uIU/ml MTSH4.2 uIU/ml MŮԻ߱gw|ָBMIտsSBP24 Сr򵰰йʣPERTSH^øwTPO-Ab׵򻼲ҕWĤ׃DRDKD ʸ߲нyӋWxIСV^ʣeGFRALB׵ףFT3FT4 нyӋWxc TSH2.5-4.2 uIU/ml MTSH4.2 uIU/ml M BMIPERTSHTPO-Ab ׵򻼲DR DKD ʸeGFRFT4 нyӋWxֵMcֵMɽMgH TSHԄeڽyӋWָ˲oyӋWx

2Logistic ؚw@ʾ SCH c DKD PδУκΣUؕrΣUȣOR95%CI 2.4081.477-3.927УgԄeBMIHbAlcTGTCHBP OR95%CI 2.1871.244-3.847ֵTSH c DKD PoyӋWx

3MgӳIСܽYԓpָ N--D-øNAGӳIСָܹβ2-΢򵰰ףβ2-MGoyӋWxTSH 2.5-4.2uIU/mlc TSH2.5uIU/mlɽMIKpָ˲oyӋWxoՓc TSH2.5uIU/ml߀ TSH 2.5-4.2uIU/mlMTSH4.2 uIU/mlMIСpָDFףTF򵰰 GIgGIСܹԓpָ RBPҕSYϵףλнyӋWxS TSH ֵpIKLȵľֵʬF½څoyӋWx

4TSH УgԄeBMIHbAlcTGTCHBPeGFRغc TFIgG P r ֵքe 0.1030.124P0.05c PERNAGRBPβ2-MG PoyӋWx

5Logistic ؚw@ʾ SCHOR=2.94495%CI 1.572-5.514c׵PŮ(OR=2.25195%CI 1.327-3.820)IΣU֌ӸΣ(OR=6.774, 95%CI 2.668-17.198)OΣ (OR=6.991, 95%CI 3.245-15.062)T2DM ߺϲ SCH ΣU

Part

1ԓо{ 582 נٹ^ T2DM DKD Ļʞ 32%co DKD MDKD MgBMITGTCSBPUABUNTSHHBP DR ʸeGFRFT3FT4 нyӋWxԄeHbAlcFBGLDL-CDBP ALTASTTPO-AbʲoyӋWx

2DKD ĻS FT3FT4 ķλ߳½څݣքe 41.535.425.528.9P=0.00641.135.928.625.7P=0.002cנټ(FT3FT4)ķֽ֔MנټصĂķλֽM DKD ĻʵнyӋWxc FT4 ķ֔FT4 ĂķλֽM׵ĻʵнyӋWxͬc FT3 ķ֔FT3 ĂķλֽM׵ĻʵнyӋWxc FT3 ķλFT3 Ăķλc DKD POR95%CI֞ 0.4830.295-0.7900.5720.351-0.933c FT4 ķλFT4 Ăķλc DKD P OR95%CI֞ 0.5730.352-0.9330.4960.3010-0.816УgԄeBMIHbAlcTGTCHBP H FT3 ķλ4.72-5.16 pmol/Lc DKD POR95%CI 0.5310.303-0.930

3 FT3FT4 ķλֽMMIKpָ˲Y@ʾcFT3 ķλֽMFT3 ĂķλֽMIKpָ TFIgGRBPβ2-MG нyӋWxc FT4 ķλֽMFT4ĂķλֽMIKpָ TFIgGRBP нyӋWxNAGָнMgoyӋWƫPУgԄeBMIHbAlcTGTCHBPeGFR FT3 c IgGTFRBPβ2-MG ؓPr ֵքe-0.168-0.152-0.137-0.142P0.01FT4 c IgG ؓPr ֵ-0.013P0.05

4FT3 ķλFT4 ķλc׵ĻؚwY@ʾУgԄeBMIHbAlcTGTCHBP غc FT3 ķλFT3 Ăķλc׵POR95%CIքe0.1520.063-0.3710.2420.111-0.531^ķλ FT4 c׵PoyӋWx



1ŮI֌ӸΣOΣ T2DM ߺϲ SCH ΣU

SCH gԄeBMIHbAlcTGTCHBP c DKD׵P

2נٹ T2DM FT3 c DKD׵PFT4 c DKD׵oP

3נٹ T2DM נټcIKpָؓP

PI~2 IK ټנټጷż נټ
Abstract
 

Objective


(1) To investigate the correlation between SCH and DKD  renal injury in patients with T2DM; (2) To explore the relationship between thyroid hormone and DKD, kidney injury indicators in T2DM patients with normal thyroid function.

Methods

Part I: A cross-sectional study was conducted on 656 patients with T2DM who were admitted to the Department of Diabetic Nephrology, Tianjin Medical University from September 2017 to February 2018. According to whether TSH>4.2mIU/l,patients were divided into normal group and SCH group, furthermore the normal group was divided into the normal low value group and the normal high value group according to whether TSH was <2.5 mIU/l. The general clinical data, glomerular damage, tubular damage, kidney size index, and the prevalence of DKD were compared in those three groups. Regression analysis of the correlation between different levels of TSH and DKD. The risk factors of macroalbuminuria. The relationship between SCH and risk stratifications of nephropathy. In addition, TSH was treated as a continuous variable to analyze the correlation with renal injury indicators.

Part II: 74 patients with SCH in the first part of the study were excluded, and 582 T2DM patients with normal thyroid function were included in this cross-sectional study. According to whether or not complicated DKD, patients were divided into non-DKD and DKD group, comparing clinical data and thyroid function test between groups. Regression analysis the relation of FT3, FT4 quartile and DKD,macroalbuminuria. Similarly, FT3 and FT4 were treated as a continuous variable to approach the relationship between thyroid hormones and renal injury indicators.

Results

Part I:

(1) The prevalence of SCH in 656 hospitalized T2DM patients was 10.3%, and the prevalence of SCH in female patients (16.1%) was significantly higher than males (8.4%). There was no significant difference in FPG, HbAlc, TG, TC, LDL-C, DBP,ALT, AST, TP, UA, BUN and the prevalence of HBP among these three groups.Compared with TSH2.5 uIU/ml grouppatients in TSH>4.2 uIU/ml group were older, longer diabetic duration, and the proportion of female, BMI, systolic bloodpressure,PER, TSH, TPO-Ab positive rate, prevalence of macroalbuminuria,DR,DKD was significant high; eGFR, ALB, FT3, FT4 were significant low. Compared with TSH 2.5-4.2 uIU/ml group, TSH>4.2 uIU/ml group BMI, PER,TSH, TPO-Ab positive rate, prevalence of albuminuria, DR, DKD were significant high; eGFR, FT4 was significant low. Except for TSH and the ratio of gender, other indicators were no significant difference between the normal low-value group and the normal high-value

group.

(2) SCH was significantly correlated with DKD, OR (95% CI) was 2.408(1.477-3.927) when no risk factors were corrected. After futher adjustments for confounding factors including age, gender, duration, BMI, HbAlc, TG, TC, HBP, OR(95%) CI) is 2.187 (1.244-3.847). normal higher TSH value was not significantly correlated with DKD.

(3) There was no significant difference among three groups in reflecting the renal tubular structural damage index NAG and reflecting the renal tubular reabsorption index β2-MG. Interestingly renal injury index did not differ betweenTSH 2.5-4.2 uIU/ml and TSH<2.5 uIU/ml groups. Whether compared with TSH<2.5 uIU/ml or TSH 2.5-4.2 uIU/ml group, TSH>4.2 uIU/ml group glomerular injury index TF, IgG, renal tubular functional injury index RBP median were significantly high. With the increase of TSH, the mean values ??of length, width and thickness of bilateral kidneys showed a downward trend, but had no significant difference.

(4) TSH was positively correlated with urinary TF and IgG after adjusting for age, gender, disease duration, BMI, HbAlc, TG, TC, HBP and eGFR factors (r values ??were 0.103, 0.124 respectively, P<0.05); While PER, NAG, RBP, β2-MG were not significantly associated with TSH.

(5) SCH (OR=2.944, 95% CI 1.572-5.514) was independently associated with macroalbuminuria; female (OR=2.251, 95% CI 1.327-3.820), high risk of stratification of kidney disease (OR=6.774, 95% CI) 2.668-17.198), T2DM patients with very high risk (OR=6.991, 95% CI 3.245-15.062) with SCH increased risk.

Part II:

(1) In this part study, the prevalence of DKD were 32% among 582 T2DM patients with normal thyroid function. Compared with non-DKD group, the DKD group patients were significant older, longer diabetic duration , higher BMI, TG, TC,SBP, UA, BUN, TSH, HBP prevalence and DR; eGFR, FT3, FT4 were significant lower. However there was no significant difference in gender ratio, HbAlc, FBG,LDL-C, DBP and ALT,AST and TPO-Ab positive rate between two groups.

(2) The prevalence of DKD shows a declining trend with the increase of FT3and FT4 quartiles (41.5, 35.4, 25.5, 28.9, P=0.006 for the trend; 41.1, 35.9, 28.6, 25.7,P =0.002 for the trend). Compared with the lowest quartile of FT3, the third and fourth quartiles of FT3 were associated with DKD, the crude OR (95% CI) were 0.483 (0.295-0.790), 0.572 (0.351-0.933) respectively.Similarly compared with the lowest quartile of FT4, third and fourth quartiles of FT4 were associated with DKD,the crude OR (95% CI) were 0.573 (0.352-0.933) and 0.496 (0.3010-0.816)respectively. After adjusting the potential factorsincluding age, gender, diabetes duration, BMI, HbAlc, TG, TC, HBP, only the third quartile of FT3 (4.72-5.16pmol/L) was associated with DKD, and the adjusted OR (95% CI) was 0.531 (0.303-0.930).

(3)Analysis of kidney injury indexes in different thyroid hormone quartiles levels showed that compared with the lowest quartile FT3kidney injury index (TF,IgG) median in the third and fourth quartile FT3 were significantly high, while RBPand β2-MG were not significantly different. Compared with the lowest quartile of FT4, third and fourth quartile of F4, which kidney injury index (TF, IgG, RBP) were significantly high. There were no significant differences in the NAG index among all groups. After adjustment for age, gender, disease duration, BMI, HbAlc, TG, TC,HBP, and eGFR, FT3 was negatively and significantly associated with IgG, TF, RBP,and β2-MG (r values ??were -0.168, -0.152, -0.137, -0.142 respectively, P<0.01);FT4 only negatively and significantly correlated with IgG (r value was -0.013

(4) Logistic regression analysis after futher adjustments for other potential confounding factors including age, gender, diabetes duration, BMI, HbAlc, TG, TC,HBP showed that the third and fourth quartile of FT3 were associated with low prevalence of macroalbuminuria in T2DM patients with normal thyroid function.

When comparing with the lowest quartile of FT3, the adjusted OR (95% CI) for macroalbuminuria were 0.152 (0.063-0.371), 0.242 (0.111-0.531) respectively.While FT4 quartile was not significantly associated with macroalbuminuria.

Conclusion

1. T2DM patients who were women, kidney disease stratification as both high risk and very high risk increased the prevalence of SCH. SCH independently of traditional risk factors was associated with DKD and macroalbuminuria.

2. In T2DM patients with normal thyroid function, FT3 was independently associated with DKD and macroalbuminuria, and FT4 was not independently associated with DKD and macroalbuminuria.

3. Thyroid hormone is negatively associated with kidney injury indicators in T2DM patients with normal thyroid function.

Keywordstype 2 diabetes, diabetic kidney disease, thyroid stimulating hormone,thyroid hormone
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^ȥĎʮDMȫ򻼲@ DM P΢ѪܺʹѪܲlYȫ򷶇ȼ[1]IKDKD DM һҪ΢ѪܲlYȺи_ 50%ĽKĩIESRD҇S򲡻ʵDKD ѳ^IСIɞIKCKDҪδпܳɞ ESRD Ҫ[2]DKD ѪܲҪΣUǺϲѪrθõķ DKD DKD ߵAǃȷڿtVPעĆ}

Ѫ DKD lMչҪQz׸ͳwصҲһנټأTHֱӰwIB|ĴxcѪǼȍuܵ{VwȵĶϵyֱӰIKLͰlIСV^ʣGFRIKD\ϵycˮwƽTH ΢С׃T TSH ָ׃TSH JǼנٹخָנٹܜp˰YSCHͨȱ@RYwϱxѪټנˮƽTSH߶Ѫ FT4TT 4 ˮƽ[3]2010 ҇ʮмנټ{@ʾ, TSH>4.2mIU/L \c,נٹܜp˵Ļʞ 17.8, SCH ʞ 16.7,Rנٹܜp˵Ļʞ 1.1[4]RtPע SCH ҪѪܼLUȫ[5]һ헰 11 ǰհоCͷ@ʾSټנˮƽԺͷԹڠ}K¼LU TSH 4.5 6.9 mIU/l 酢TSH 7.0 9.9mIU/L Լ TSH 10.0 19.9mIU/L ֮gĻOR 95CI քe 1.170.961.431.891.282.80[6]

SCH c΢Ѫܲ׃PоԽԽYasuda [7]оlF SCH ׵cֵUACRڼנٹTSH T2DM ΢׵ĪΣUIKIСƤϵK΢Ѫͨ͸F΢׵΢׵ϵyѪ܃ƤϵKָҲ DKD һҪ־헙MоY֧ SCH c DKD PnW Kim [8]о SCH cضҕWĤ׃DRPc DKD oPһCͷ@ʾSCH cDKD P OR 95CI 1.741.342.28 DKD \ȱخԵĘ˜ʺָ󲿷оHÆδΰ׵x DKD@оY|Եԭ֮һ

Sנٹܮ΢Ѫܲ׃PԽԽܵPע˂ߵPעєUչנٹIWu [9] 421 נT2DM ߵęMоlFנٹ T2DM Ѫ FT3 ˮƽcDKDUACR ʪؓPc DR oPZou [10]оּ֧נٹ T2DM FT3 ˮƽc DKD ؓPȻڌԄeMз֌ӺFT3 DKD PŮԻвRﻯWоԺlČָ@ʾ95%ϵ TSH ˮƽ 2.5 mIU/Lֵ^ߵĮֵǘ򱾼נ׻ԭ TSH [11]ЌWԓ TSH ޶x飼2.5mIU/L[12]Qi [13]оlFȵĸ TSH c DKD PĿǰֹȵĵ FT3 TSH c DKDPԵоH 4 MSCH DKDIp֮gPϵ^ȥĎȵõԔuYՓδyһȵļנPغ DKDIpָ֮gPC^߀ҪRCC
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DKD llչҪԭǸѪ҂Mһנٹܺ򲡵PϵԼנټIKFPīIоṩPՓ֧

1. נٹܺ

һЩǰհԵоlFנٹԇѪ TSH ͣ򣩼נټصˮƽ׃c T2DM İlP¹صһȺAĴǰհоlFƽSL 7.9 נٹܜp򲡵İlLUʹנٹڅ^ߵ TSH 򲡵İlLU(HR1.2495% CI 1.06–1.45log TSH)^ߵ FT4 򲡵İlLU(HR 0.96;95%CI 0.93–0.99, ÿ 1 pmol/L)[14]nһԼנٹĽwzߞоMеǰհоlF TSHנټصIJ T2DMlLUλ TSHנټˮƽc T2DM oP[15]ͬנټˮƽ T2DM ֮gPϵдڠh[16]נټc֮g“ϵĝڲCδõU^쵽ļנٹܵcLU֮gPϵܿͨ^ŽׂCƽŔRנٹܜpcȍuԽȍuصֿPנټίԻ֏ȍuԺȍu׿صķ[17,18]C{ĤD\wֱӰȍuؽ[17]נٰ(T3)ѱCЅcoȍuβ-[20]נٹܜpcxCPgӵ򲡵İlLU[21]

෴оlFT2DM Ѫǿ^Ļ߻ SCH LU^ˮƽߌX-w-נSĴ̼T2DM PװYcנټخPwȵÓøĻʧⅢc[22]נٹc T2DM ֮gǏs໥õpPϵ[23]

2.נټIKF

נټ؎׺ӰwȵÿϵyXጷŵ TRH ͨ^wT}ϵy̼ٴw TSHTSH ̼נٞVנټغϳcɼנٞVݺϳɷڵѪѭhеĻҪмנ (T4)ԭ (T3)քeռڿ 937߀ИOoԵĻ-ԭ (rT3)T4 Hɼנٮa T3 ǼנټصʽҪMаIK T4 ͨ^ 5-ÓøֲÓaѪҺ 80 T3 Դ T4 ÓנֱӷנټҪͨ^cנټغwYϰl]Ȼͨ^cлļנټطԪYρӰ푻DנټҲͨ^c|Ĥ|򼚰ȲλĸH TH Yϵλcl]ǻMЧ[24]

2.1 נټIKLlӰ

ڄנټؿڰlڼAӰIKСͽYMWоנټ،Ƥ||IСܹ܏aӰ؄e漰Сֶ֧cIСS๲D\ϵyİl{נٹܜp˰YIĴССLȺֱԼijN̶ϵIСwe[25]چ΂IгgIKģנٹܜp˰YҲpԷʴ[26]

2.2 נټIСӰ

נټͨ^׃ѪWIKYֱӐIנٹܜpͰSGRFGRFһmIСǰѪտsڽIСcˮղĞVҺ^d GFRшڼנٹܜp˰YIѪܔUѪ܃ƤLӣVEGFȍuؘL-1IGF-1ı_[27]IѪտsܽIѪIܐڄנٹܜpcIK/CwwָpٺIС׃ԼIСYIJ׃PRоڼנٹܜp˰YIСëѪ܌׵׵ĝB͸נٿwԵĻcנٿwԻ׵й[28]ߏͺeIСĤ׃IԙCƿ܅cIСēp
ڱƪžTʿՓȫՈcײdȫ朽ӡ

1.1.3 yӋW

1.2 Y
1.2.1 TSH ֽͬMRYϱ^
1.2.2 TSH ͬˮƽ DKD P
1.2.3 TSH ֽͬMIKpָ˱^
1.2.4 TSH ֽͬMpIKС^
1.2.5 TSH cIKpָ˵PԷ
1.2.6 ׵ΣU
1.2.7 SCH cIΣU֌ӵP

1.3 ӑՓ

1.4 СY

2נټcIKIpָ˵Pԣנٹ T2DMߣ

2.1 ͷ

2.1.1 о
2.1.2 о
2.1.3 yӋW

2.2 Y
2.2.1 DKD co DKD ߵR^
2.2.2 נټķλֽM DKD׵򻼲r
2.2.3 נټķλֽMc DKD PԷ
2.2.4 נټķλֽMIKpָ˱^
2.2.5 נټcIKpָ˵PԷ
2.2.6 נټc׵PԷ

2.3 ӑՓ

2.4 СY

1ŮI֌ӸΣOΣ T2DM ߺϲ SCH ΣUSCH gԄeBMIHbAlcTGTCHBP c DKD׵P

2נٹ T2DM FT3 c DKD׵PFT4 c DKD׵oP

3נٹ T2DM נټcIKpָؓP

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