| BackgroundThyroid diseases and diabetes mellitus are the two most common endocrine disorders encountered in clinical.The prevalence rate of thyroid dysfunction is much higher among diabetic population and estimated to be from 6.9%to 16%.However,many researchers have reported that most of T2DM patients have normal thyroid function.Thyroid hormone has multiple effects on the regulation of lipid metabolism.Studies have shown that subclinical hypothyroidism(SCH)can increase the risk of dyslipidemia and atherosclerotic cardiovascular disease.A series of studies reported that variations of serum thyroid stimulating hormone(TSH)levels within the normal reference range were related to triglycerides(TGs),total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C).Latest research found that TSH may increase the expression of hepatic3-hydroxy-3-methyl-glutaryl coenzymeA reductase(HMGCR),suggesting a potential direct role of TSH in cholesterol synthesis in the liver.Furthermore,numerous studies have found the serum free thyroxine(FT4)levels within the reference range were associated with different metabolic markers in euthyroid patients.Recently,several researches have reported that relative low thyroid functions within normal range were more frequent and might lead to blood lipid metabolism disorders,insulin resistance in diabetic patients.However,the prevalence of diabetes is increasing in our country,only a few studies which concerned the relationship between thyroid within the normal range and lipids in T2DM can be found,In addition,in most reports,TSH,FT4 and free triiodothyronine(FT3)were not studied together.Therefore,the purpose of this study is to study the underlying association between thyroid hormone levels,antithyroid antibody and dyslipidemia in euthyroidnew-diagnosed type 2 diabetic patients.We hoped this study would lead to a better understanding the role of thyroid parameters and antithyroid antibody in blood lipid metabolism in diabetes mellitus.Objective1.To explore correlations between serum thyroid stimulating hormone(TSH)concentration within the normal range and lipids metabolism in new-diagnosed type 2 diabetic patients.2.To explore correlations between free thyroxine(FT4)and free triiodothyronine(FT3)concentration within the reference range,FT3/FT4 ratio and lipids metabolism in new-diagnosed type 2 diabetic patients.3.To observe the effect of positive antithyroid antibody on thyroid hormone and lipids metabolism in new-diagnosed type 2 diabetic patients.Subjects and Methods1.SubjectsAll of the patients were from inpatients of Department of Endocrinology,the Affiliated YantaiYuhuangding Hospital of Qingdao University.A total of 1106 patients participated in the investigation.According to the study criteria of New-diagnosed T2DM and Euthyroidism,404 individuals(212males and 192 females)were included in the study.We divided diabetic patients with normal thyroid function into four categories:G1(TSH 0.27-1.19mIU/L),G2(TSH 1.2-1.89mIU/L),G3(TSH 1.9-2.49mIU/L)and G4(upper limits of TSH 2.5-4.2mIU/L)according to epidemic ecological studies.All the euthyroid patient were also categorized into two groups according to the levels of FT4:Lowest(12-16.9pmol/L),Highest(17-22pmol/L).2.Anthropometric measurementsThe height,weight of each group were measured in the fasting state.The body mass index(BMI)was calculated as the weight in kilograms divided by the height squared in meters.Each patient had a rest for 15 minutes in a supine state.The blood pressure of the right upper limb was measured by the desk sphygmomanometer.The interval was 2-3 minutes,and two times were taken.The mean value was used as the result of systolic blood pressure(SBP)/diastolic blood pressure(DBP).The laboratory test was used to collect blood for more than 8 hours on the patient’s empty stomach.3.Laboratory measurementsThe levels of TSH,FT4,FT3,thyroglobulin antibody(TGAb)and thyroid peroxidase antibody(TPOAb)were measured by usingchemilumines-cence tests.Glycosylated HemoglobinA1c(HbA1c)levels were measured by high pressure liquid chromatography.Triglycerides(TGs),total cholesterol(TC),,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),apolipoproteinB(ApoB),apolipoproteinAl(ApoAl)andfasting plasma glucose(FPG)were determined using an Auto Biochemical Analyzer.FFA(Free fatty acid)was measured by ELSIA Fatty Acid Assay Kit.4.Statistical analysisData are presented as mean ± standard deviation(SD)for continuous variables.Differences in proportions of variables were determined by chi-squared analysis.Statistical analysis was performed to a multiple comparison for subgroup analysiswith ANOVA.Pearson’s correlation analyses was used to examine the relationships between thyroid hormones and lipid parameters.A partial correlation analysis were performed while evaluating the relationship between TSH,FT4 and lipid after adjustment for sex,age and FPG.Multiple linear regression analysis was used to estimate the impact of TSH and FT4 on lipid metabolism.The statistical analyses were performed using SPSS software.Statistical significance was defined as P<0.05.Results1.56%of the participants were moderately overweight(BMI>25 kg/m2)and 13.7%were obese(BMI>30 kg/m2).Fasting blood glucose levels in 83.5%of patients were less than 10mmol/L.The average HbAlc level was 8.56 ± 1.39%.Forty-six subjects were positive for either TGAb orTPOAb.Nineteen of these subjects were positive for TPOAb only,twenty-one of subjects were positive forTGAb only and six subjects were positive for both TPOAb and TGAb.2.Pearson’s correlation analyses showed that TSH levels were positively associated with serum TC,LDL-C,ApoAl and ApoB levels.Significant negative correlations were identified between FT4 and serum TC,TG,LDL-C and ApoB levels.The correlations remained significant after we adjusted for age,gender and FPG.FT3/FT4 ratio was correlated with TC,TG and ApoB.Different from the results of the FT4,there was no correlation between the FT3/FT4 ratio and LDL-C.There was no significant relationship between FT3 and lipid.3.A multiple linear regression analysis results revealed that in type 2 diabetic patients with euthyroidism,within the normal range,TSH significantly associated with TC(β = 0.258,P<0.001),LDL-C(β = 0.226,P<0.001),ApoA1(β = 0.132,P = 0.006)and ApoB(β= 0.263,P<0.001),while FT4 significantly associated with TC(β =-0.105,P = 0.030),TG(β =-0.104,P = 0.029)and ApoB(β =-0.106,P = 0.030).The FT3/FT4 ratio was independently associated with TC,TG and ApoB.4.Comparison of Clinical characteristics among different TSH categories within the normal range.The results showed no significant differences existed concerning age,sex,levels of FBG,HbA1c,SBP,DBP,FT4 and FT3 among the four TSH categories.BMI in G3 was significantly higher than that in G2.The levels of TC,LDL-C,ApoA1 and ApoB in G4 and G3 were significantly higher compared to G1 and G2 respectively.TG in G3 was significantly higher than that in Gland G2.With the elevated of TSH levels within the normal range,TC,LDL-C,ApoA1 and ApoB levels also showed a gradual increasing trend.This trend maintained substantially in HDL-C levels,which in G4 were higher than that in G1,but no significant differences among the TSH categories.No significant differences existed among the levels of FFA of the four TSH categories.5.All the subjects were categorized into two groups according to levels of FT4,Lowest group(12-16.99 pmol/L),Highest group(17.0-22.0 pmol/L).The results showed that serum TC,TG,LDL-C and ApoB were higher in Lowest group than those in Highest Group.FT4 in highest group accompanied by a marked increase in FT3 levels(4.78 ± 0.75 vs.4.42 ± 0.74 pmol/L,P<0.01),but no difference in TSH between two groups.There were no difference between the two groups such as gender,age,blood pressure,HbAlc,HDL-C,ApoA1 and FFA.6.Comparison the changes of thyroid hormone and serum lipids in patients with anti-thyroid antibody positive and negative.Of the 404 patients,46(11.38%)were antithyroid antibody positive and 358(88.62%)were negative.FT4 levels in antibody positive patients were significantly lower than those in antibody negative patients(15.87 ± 2.32pmol/L vs.16.63 ± 2.20pmol/L;P<0.05).TSH and FT3 levels were not significantly different between two groups.Lipid including TC,LDL-C,TG,ApoA1 and ApoB levels in antibody positive patients were higher than those in antibody positive patients.However,there was no significant difference.Conclusions1.High-normal TSH level was positively correlated with the hypercholesterolemia and elevated apolipoproteinslevels in new-diagnosed type 2 diabetic patients.2.Low serum FT4 level was associated with hypertriglyceridemia and elevated apolipoprotein B,increased FT3/FT4 ratios are associated with TC,TG and ApoBin euthyroid new-diagnosed type 2 diabetic patients..3.Along with significantly lower FT4 and slightly elevated TSHlevelsin antithyroid antibody positive groups.Higher lipid concentrations were also observed inantibody positive groups,but the differences were not significant.4.Higher TSH with lower FT4 in normal range and the higher FT3/FT4 ratio could also exert adverse effects on the lipid profile and increase atherosclerosis susceptibility innew-diagnosed type 2 diabetic patients. |
