| Background and purposeMetformin, which has been treated as the first-line drug for DM in multiple domestic and overseas guidelines, is a kind of hypoglycemic drugs with good safety that is extensively applied in clinical practice. In recent years, more and more importance has been attached to the research on the connection between metformin and thyroid diseases. Some retrospective studies discovered that metformin inhibited the secretion of thyroid-stimulating hormone(TSH) in the serum of patients with hypothyroidism, and made no difference to thyroid hormone level. However, a majority of these studies came from patients with polycystic ovarian syndrome or obesity, and research on the effects of metformin on the serum TSH level in patients with T2 DM was so little that whether there was gender difference of the effects had not been reported yet, as a result, the way in which metformin affected serum TSH remained to be further explored. The research aims to compare the effects of metformin and non-biguanides on serum TSH levels of patients with T2 MD combined with SCH, analyzes the role of gender difference, and preliminarily discusses the mechanism.Methods97 cases of patients with SCH were selected from the 735 cases of newly-diagnosed patients with T2 MD. Divided the 97 patients with T2 MD combined with SCH into biguanide group(group 1) and non-biguanide group(group 2) on the basis of use of metformin. 35 cases of patients with T2 MD that had matched age and body mass index(BMI) with normal thyroid functions through biochemical and color doppler ultrasound examination were treated as control group(group 3). The same dosage of metformin was applied orally in the control group. All patients received no levothyrocine(L-T4) therapy. A 6-month follow-up was conducted monthly during treatment to study the medication, diet and exercise of patients.The height, weight, waistline, abdominal height, BMI, waist-height ratio(WHtR), fasting plasma glucose(FPG), blood glucose two hours after oral glucose tolerance test(OGTT-2h), glycosylated hemoglobin(HbA1c), insulin, homeoestasis model assessment of insulin resistance(HOMA-IR), blood lipid [total cholesterol(TC), triglyceride(TG) and high density lipoprotein cholesterol(HDL-C)], and thyroid functions [serum TSH, free triiodothyronine(FT3) and free thyroxine(FT4)of the patients before and after treatment were compared.Results(1) There were no statistical differences of the age, weight, BMI, WHtR,abdominal height, blood lipid(TG, HDL-C and TCHO), HbA1 c,FPG and HOMA-IR of patients in the three groups before treatment(F=0.745~2.385,P>0.05). The blood glucose two hours after oral glucose tolerance test in group 1 and group 2 were higher than that in group 3, and the difference was of statistical significance(P<0.05). The difference of the serum TSH levels in group 1 and group 2 was of no statistical significance(P>0.05), and the differences of the serum FT3 and FT4 levels in the three groups were of no statistical significance(P>0.05).(2) The weight and BMI decreased in the three groups after 6-month treatment,however, the differences were of no statistical significance(P>0.05). The WHtR in group 1 reduced to a certain extent, while group 2 and group 3 showed no obviouschanges. The decrease of abdominal height in group 1 was significantly greater than that in group 2 and group 3(P<0.05), and the difference was of statistical significance.(3) The FPG, blood glucose two hours after oral glucose tolerance test, HbA1 c and HOMA-IR in three groups significantly reduced after 6-month treatment when compared with those before treatment(P<0.05), and the differences were of statistical significance.(4) After 6-month treatment, the serum TSH level in group 1 reduced significantly than that before treatment(P<0.01), and it reduced greater in female than in male, with statistical difference(P<0.05), while the FT3 and FT4 levels showed no difference before and after treatment. The serum TSH, FT3 and FT4 levels showed no obvious difference in group 2 and group 3.(5) Relevant analysis indicated that the variation of TSH was negatively correlated with gender and HOMA-IR, but was positively correlated with the variation of abdominal height. Multiple stepwise regression analysis revealed that gender(P<0.01)and abdominal height(P<0.01)were the independent influence factors of TSH variation.Conclusions(1) Metformin may decreased serum TSH levels in patients with type 2 diabetes combined with subclinical hypothyroidism,,and has no significant effects on Free Triiodothyronine(FT3)and Free Thyroxine(FT4).(2) Metformin decreases the serum TSH level in patients with T2 DM combined with SCH, which may be related to reducing the accumulation of visceral fat and improving abdominal obesity. The above-mentioned changes have gender differences,with the serum TSH level decreasing more obviously in female users. |
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