Association Of Thyroid Hormones With Diabetic Kidney Disease

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 T2 DM patients with normal thyroid function.MethodsPart I: A cross-sectional study was conducted on 656 patients with T2 DM 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,and582 T2 DM 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 T2 DM patients was 10.3%,andthe 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 TSH<2.5 uIU/ml group,patients in TSH>4.2 uIU/ml group were older,longer diabetic duration,and the proportion of female,BMI,systolic blood pressure,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 ?2-MG.Interestingly renal injury index did not differ between TSH 2.5-4.2 uIU/ml and TSH<2.5 uIU/ml groups.Whether compared with TSH<2.5uIU/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,?2-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 ofstratification of kidney disease(OR=6.774,95% CI)2.668-17.198),T2 DM 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 T2 DM 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 FT3 and 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)were0.483(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 factors,including 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 FT3,kidney injury index(TF,IgG)median in the third and fourth quartile FT3 were significantly high,while RBP and ?2-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 ?2-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,P<0.05).(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 T2 DM 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.Conclusion1.T2 DM 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 T2 DM 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 T2 DM patients with normal thyroid function.