Effect Of Metformin On Thyroid Function In Patients With Type 1 Diabetes Mellitus

Objective:To observe the prevalence of thyroid disease,changes in serum thyroid hormones,and thyroid autoantibody before and after treatment with metformin on insulin basis in patients with type 1 diabetes mellitus（T1DM）.To investigate the effect of metformin on thyroid function in patients with T1DM and reveal the role of metformin in addition to lowering blood glucose.Methods:A total of 199 patients with T1DM who met the inclusion criteria and were treated in the outpatient department and inpatient department of the Endocrinology Department of the First Hospital of Lanzhou University from January2014 to June 2019 were selected.The patients’medical history was collected in detail and clinical data such as gender,age,history of diabetes,history of thyroid disease,and diagnosis and treatment of diabetes were collected.Fasting plasma glucose（FPG）,glycosylated hemoglobin（HbA1c）,body mass index（BMI）,liver function,kidney function,serum homocysteine（Hcy）,and Biochemical indicators such as blood lipid metabolism,and serum thyroid hormone and antibody levels are measured at the same time,including serum free triiodothyronine（FT₃）,serum free thyroxine（FT₄）,and thyroid stimulating hormone（TSH）,thyroid peroxidase antibody（TPOAb）,thyroglobulin antibodies（TgAb）.The effects of different genders on the level of thyroid function and the prevalence of thyroid disease in patients with T1DM were analyzed.Based on the use of insulin to control blood glucose,all T1DM patients were divided into insulin+metformin group and insulin group according to whether or not metformin was added.Observe the prevalence of thyroid disease,serum thyroid hormone and related factors in T1DM patients before and after adding metformin treatment.Antibody levels,and further analyze and compare the effects of different doses of metformin on thyroid function in patients,and explore the effect of metformin on thyroid function in patients with T1DM.Statistical analysis was performed using SPSS23.0 statistical software.Results:1.Comparison of general conditions of patients enrolled before treatment:compared with the insulin group,the age,number of diabetes complications,FPG,HbA1c and BMI of patients in the insulin+metformin group were all higher than those in the insulin group（P<0.05）.There was no significant difference in gender,diabetes course,hcy,liver function,kidney function and lipid metabolism between the two groups（P>0.05）.2.Comparison of thyroid function levels and prevalence rates between male and female groups showed that serum TSH level and prevalence of thyroid disease were higher in women than in men（14.3%vs.7.4%）,but there was no statistical significance（P>0.05）.There was no significant difference in serum FT₃ and FT₄ levels between the two groups（P>0.05）.3.The prevalence of thyroid disease was compared between the two groups before and after treatment:the total prevalence of thyroid disease in all the enrolled T1DM patients was 10.6%（21/199）,and the clinical manifestations were mainly subclinical hypothyroidism（8.0%）,with statistically significant difference（P<0.001）.There was no significant difference in thyroid prevalence between the groups of metformin and insulin before treatment,insulin+metformin group and insulin group after treatment,insulin+metformin group before and after treatment,and insulin group before and after treatment（P>0.05）.4.Comparison of thyroid function status between T1DM patients before and after treatment:after treatment,compared with the insulin group,FT₄ and TSH levels in the insulin+metformin group were higher than those in the insulin group（P<0.05）.After treatment,FT₄ level in insulin+metformin group was higher than that before treatment,and TPOAb level was lower than that before treatment（P<0.05）.5.To analyze and compare the effect of thyroid autoantibodies between T1DM patients before and after treatment:the positive rate of TPOAb was 14.6%and the positive rate of TgAb was 17.1%.The positive rate of TPOAb or TgAb antibody in insulin+metformin group after treatment was lower than that in insulin+metformin group before and after treatment（P<0.05）.After treatment,the positive rate of TPOAb or TgAb antibody in insulin+metformin group was lower than that in insulin group（P<0.05）.6.According to the different dose of metformin,the insulin+metformin group was divided into four groups:500 mg,750 mg,1000 mg and 1500 mg,and the effects of different doses of metformin on thyroid function in patients with type 1 diabetes were analyzed and compared.The serum TSH and TgAb levels decreased with the increase of the dose of metformin（P<0.05）.7.Spearman correlation analysis:FT₃ was correlated with gender,number of diabetes complications,HbAlc,Total cholesterol（TC）,and positively correlated with gender and number of diabetes complications（r=0.308,0.414,both P<0.01）,and negatively correlated with HbAlc and TC（r=-0.253,-0.229,P<0.05）.FT₄ was positively correlated with gender and FPG（r=0.247,0.245,both P<0.05）,and negatively correlated with TC（r=-0.191,P<0.05）.TSH was negatively correlated with age,diabetes course and metformin（r=-0.234,-0.210,-0.619,P<0.05）.The correlation between TBOAb and metformin and HbAlc was significant and negative（r=-0.302,-0.291,P<0.01）.TBOAb was positively correlated with TC（r=0.229,P<0.01）.8.Taking FT₃,FT₄,TSH,TBOAb,and TgAb as dependent variables,the correlation between metformin and diabetes status and serum thyroid hormone level in T1DM patients was further analyzed by using multiple linear stepback regression method.Metformin was independently correlated with TSH and TgAb.Metformin was independently correlated with serum TPOAb and TgAb levels（-1.523,-5.754,P=0.001,0.046）.Conclusion:1.The prevalence rate of T1DM patients with thyroid diseases is 10.6%,mainly subclinical hyperthyroidism,followed by hypothyroidism,and finally subclinical hyperthyroidism.The treatment with metformin could reduce the prevalence of hypothyroidism and subclinical hypothyroidism.2.Serum TSH and TgAb levels decreased with the increase of metformin dose.Metformin can affect the thyroid function level of T1DM patients to a certain extent,which will increase the serum FT₄ level and reduce the serum TSH level,suggesting that metformin may be a protective factor for TSH level of T1DM patients.3.Metformin not only has a good effect on reducing blood glucose in T1DM,but also has a certain effect on TSH and TgAb,which may prevent hypothyroidism and reduce the occurrence of hypothyroidism.