Study On The Correlation Between Thyroid Hormone Levels In Early Pregnancy And Gestational Diabetes Mellitus

Objective To investigate the association of first trimester levels of thyroid stimulating hormone（TSH）,free thyroxine（FT4）,thyroid peroxidase antibody（TPOAb）and thyroid diseases with gestational diabetes mellitus（GDM）and blood glucose levels of oral glucose tolerance test（OGTT）,providing a scientific basis for the prevention and treatment of GDM.Methods A nested case-control study method was used based on a birth cohort.Pregnant women who completed registration,antenatal care,and delivery at the Gansu Maternal and Child Health Hospital from October 2018 to December 2020 were selected as the study subjects.General demographic characteristics were collected through a questionnaire survey.The thyroid hormone levels in early pregnancy were measured by electrochemical luminescence immunoassay（ECLIA）.The results of the OGTT were followed up during 24～28 weeks of pregnancy.1.Logistic regression models were applied to estimate the associations of the levels of thyroid hormones with GDM.2.Generalized linear regression models were applied to analyze the relationship between the thyroid hormones and blood glucose levels of OGTT.3.Restricted cubic spline（RCS）models were used to establish the dose-response association curves of the levels of thyroid hormones with the risk of GDM and blood glucose levels of OGTT.4.Stratified analysis was performed to estimate the potential impact of different characteristics on the relationship between the thyroid hormones and GDM.Results 1.A total of 3158 pregnant women were included in this study,and the prevalence of GDM was 10.13%.There were 320 GDM pregnant women and 2838non-GDM pregnant women.The TSH and TPOAb levels of the GDM group were higher than those of the non-GDM group,while the FT4 levels of the GDM group was slightly lower than those of the non-GDM group,and the differences were statistically significant（P<0.05）.2.Compared with the group with the lowest TSH level（≤2.50 mIU/L）,the risk of GDM increased in both the group with 2.50 mIU/L<TSH≤4.00mIU/L and the group with TSH>4.00 mIU/L,while the adjusted OR values（95%CI）were 1.51（1.15～1.99）and 2.61（1.89～3.74）,respectively.The results of the RCS curves analysis showed a positive linear dose-response relationship between TSH concentration and the risk of GDM(P_overall<0.001,P_nonlinear=0.857).In addition,the risk of GDM increased by 24%for each 1-unit increase in TSH,and the fasting blood glucose,1-hour blood glucose,and 2-hour blood glucose levels of pregnant women in the OGTT increased by 0.02,0.10,and 0.07 mmol/L,all with statistically significant differences（P<0.05）.3.Compared with the lowest quartile of FT4 concentration（Q1）,the highest quartile（Q4）showed a 35%reduction in the risk of GDM（OR=0.65,95%CI=0.37～0.75）.The results of the RCS curves analysis showed a non-linear dose relationship between FT4 levels and the risk of GDM(P_overall<0.007,P_nonlinear=0.027).In addition,for each 1-unit increase in FT4 concentration,maternal OGTT 1-hour glucose decreased by 0.02 mmol/L,with a statistically significant difference（P<0.05）,and OGTT fasting glucose and 2-hour glucose both decreased by 0.01 mmol/L,but the differences were not statistically significant（P>0.05）.4.Compared with TPOAb-negative pregnant women,pregnant women with TPOAb-positive showed an increased risk of GDM,with an adjusted OR value（95%CI）of 1.55（1.04～2.29）.The 1-hour and 2-hour blood glucose levels of pregnant women in the OGTT increased by 0.21 and 0.16 mmol/L,and the differences were statistically significant（P<0.05）.But there was no significant difference in OGTT fasting blood glucose levels（P=0.303）.In addition,the combination of TPOAb positivity and elevated TSH（>2.50 mIU/L）further increased the risk of GDM,with an adjusted OR value（95%CI）of 2.49（1.51～4.14）.5.The risk of GDM was increased in pregnant women with clinical hypothyroidism and subclinical hypothyroidism（SCH）,with adjusted OR values（95%CI）of 2.90（1.35～6.23）and 2.42（1.69～3.47）.No association was found between hypothyroidism and GDM.Conclusions 1.There was a linear positive correlation between early pregnancy TSH concentration and the risk of GDM.In addition,fasting blood glucose,1-hour blood glucose,and 2-hour blood glucose levels in the OGTT all increased with increasing TSH concentration in early pregnancy.2.There was a non-linear dose-response relationship between FT4 concentration and the risk of GDM in early pregnancy,and higher FT4 levels（≥17.91 pmol/L）reduced the risk of GDM.In addition,elevated FT4 concentrations in early pregnancy were associated with lower OGTT 1-hour glucose levels.3.TPOAb positivity increased the risk of GDM,and TPOAb positivity combined with elevated TSH（>2.50 mIU/L）further increased the risk of GDM.In addition,TPOAb positivity was associated with elevated OGTT 1-hour and 2-hour glucose levels.4.Both clinical hypothyroidism and SCH increased the risk of GDM.In addition,clinical hypothyroidism was associated with elevated OGTT fasting glucose and 1-hour glucose levels,while SCH was associated with elevated OGTT fasting glucose,1-hour glucose and 2-hour glucose levels.