The Relationship Between Thyroid Function With Atherosclerosis In Type 2 Diabetes Under Different Thyroid Peroxidase Antibody Levels

Objective:Type 2 diabetes mellitus（T2DM）is a common chronic disease.Diabetic macroangiopathy is one of the common chronic complications of T2DM,of which the main pathological change is atherosclerosis（AS）.Foreign epidemiological statistics showed that the prevalence of thyroid dysfunction in T2DM patients ranged from 12.5%to 16.0%,which was about 2 to 3 times than that in non-diabetic patients.Subclinical hypothyroidism（SCH）was the most common disease among thyroid dysfunctions,with a prevalence of 10.2%.Hypothyroidism was known to increase the risk of cardiovascular disease in diabetes,and many studies in recent years had proposed that SCH was also associated with atherosclerosis in patients with T2DM.Hashimoto’s disease is one of the most important causes of hypothyroidism.Thyroid peroxidase antibody（TPOAb）,the hallmark antibody of Hashimoto’s disease,was an important predictor of hypothyroidism.In this study,we retrospectively analyze and compare the clinical datas of T2DM patients with normal thyroid function and SCH.Aming to explore the relationship between TPOAb levels and atherosclerosis in T2DM patients with SCH,that provides a basis to consider an early intervention to mitigate the occurrence and development of diabetic macroangiopathy in SCH and TPOAb positive patients.Methods:839 patients with type 2 diabetes aged between 18 and 75 years who were hospitalized at the First Affiliated Hospital of Dalian Medical University of Endocrinology from January 2017 to December 2019.According to the level of serum TPOAb levels,the patients were divided into TPOAb positive group（TPOAb>60 IU/ml）or TPOAb negative group（TPOAb≤60 IU/ml）.Each group was divided into two sub-groups according to the normal（0.38-4.34μIU/ml）or increased（>4.34μIU/ml）levels of serum thyroid stimulating hormone（TSH）.As a result,the total patients were divided into four groups:（1）TPOAb-negative group with normal thyroid function,which was TPOAb-negative and had normal TSH level;（2）TPOAb-negative group with SCH,which was TPOAb-negative and had increased TSH level;（3）TPOAb-positive group with normal thyroid function,which was TPOAb-positive and had normal TSH level;（4）TPOAb-positive group with SCH,which was TPOAb-positive and had increased TSH level.The patients’characters including gender,age,duration of diabetes mellitus,smoking history,the application rate of lipid-regulating or anti-platelet aggregation drugs,systolic blood pressure（SBP）,diastole pressure（DBP）,body mass index（BMI）,waist hip ratio（WHR）,visceral fat area（VFA）,subcutaneous fat area（SFA）,fasting plasma glucose（FPG）,glycated hemoglobin A1c（Hb A1c）,total cholesterol（TC）,triglyceride（TG）,low-density lipoprotein（LDL-C）,TSH,free triiodothyronine（FT₃）,free thyroxine（FT₄）,carotid intima-media thickness（CIMT）and carotid plaque between groups were compared.SPSS 22.0 was used to statistically analyze the differences in each index between the groups.Multivariate logistic regression was used to analyze the risk factors for atherosclerosis in T2DM.Results:1.Compared with TPOAb-negative group,serum FT₃ levels（4.63±0.62 vs4.72±0.51 pmol/L,P<0.05）of TPOAb-positive group were lower,and serum TSH levels[2.49（1.65～3.74）vs 1.92（1.33～2.70）μIU/ml,P<0.05],serum TC levels[5.05（4.34～5.93）vs 4.79（4.08～5.51）mmol/L,P<0.05],the ratio of CIMT thickening（83.3%vs 74.8%,P<0.05）and the application rate of lipid-regulating or anti-platelet aggregation drugs（58.3%vs 71.9%,P<0.05）were higher.There was no statistical significance in differences of gender ratio,smoking ratio,age,disease duration,SBP,DBP,BMI,WHR,VFA,SFA,FT₄,FPG,Hb A1c,TG,LDL-C or carotid plaque between two groups（P>0.05）.2.Serum TC levels[5.75（5.01～6.15）vs 4.81（4.12～5.56）mmol/L,P<0.05]and LDL-C[3.16（2.68～3.55）vs 2.65（2.15～3.11）mmol/L,P<0.05]of TPOAb-positive group with SCH were significantly higher than those of TPOAb-negative group with normal thyroid function,serum FT₃ levels（4.37±0.55 vs 4.83±0.55 pmol/L,P<0.05）of TPOAb-positive group with SCH was significantly lower than that of TPOAb-negative group with subclinical hypothyroidism.There was no statistical significance in differences of gender ratio,smoking ratio,age,disease duration,SBP,DBP,BMI,WHR,VFA,SFA,FT₄,FPG,Hb A1c,TG,carotid plaque or CIMT thickening ratio among four groups（P>0.05）.3.Binary logistic regression analysis was performed with carotid plaque and CIMT thickening as dependent variables,respectively,and age,gender,duration of diabetes,smoking history,BMI,SBP,DBP,WHR,VFA,SFA,FPG,Hb A1c,TG,TC,LDL-C,TSH,FT₃,FT₄,TPOAb positivity as independent variables.After adjusting for other influencing factors,gender,age,SBP,DBP and serum FT₃ levels were the influencing factors of carotid plaques（P<0.05）.Among these influencing factors,high levels of serum FT₃ within normal ranges,the gender of female and increasing DBP were the protective factors of carotid plaques.Increasing age and SBP were the risk factors of carotid plaques.Gender,age,SBP,Hb A1c and TPOAb positivity were the influencing factors of CIMT thickening（P<0.05）,of which female gender was a protective factor for CIMT thickening.TPOAb positivity,Aging,increasing SBP and Hb A1c were risk factors for CIMT thickening.Conclusions:1.Serum TSH,TC levels and the ratio of CIMT thickening in TPOAb-positive patients are increased compared with with those in TPOAb-negative patients while serum FT₃ levels are decreased.TPOAb-positive is an independent risk factor of CIMT thickening.TPOAb may promote CIMT thickening,and this correlation may be partially independent of thyroid function.2.Patients with T2DM and SCH have significantly lower serum FT₃ levels and significantly higher TC and LDL-C when their TPOAb is positive.Lower serum FT₃levels within the normal range are a risk factor for carotid plaque.TPOAb may promote the formation of carotid plaques by affecting the level of FT₃ and blood lipid.