Correlation between thyroid stimulating hormone and hyperhomocysteinemia in euthyroid type 2 diabetes mellitus patients

Objective：To investigate the potential correlation between thyroid stimulating hormone and hyperhomocysteinemia (HHcy) in a cohort of euthyroid type 2 diabetes mellitus (T2DM), and explore other related risk factors for HHcy. Methods：From January 2016 to June 2017, 108 patients with euthyroid T2DM (56 males and 52 females) were enrolled in the Department of Endocrinology, the Second People’s Hospital. Fifty age- and gender-matched healthy volunteers were served as controls. Clinical characteristics such as body mass index (BMI), glycosylated hemoglobin (HbA1c), serum biochemistry parameters, thyroid function, fasting C-peptide were recorded. Fasting insulin resistance (HOMA-IR) was derived from C-peptide and estimated glomerular filtration (eGFR) was calculated using CKD-EPI formula. Serum homocysteine (Hcy) level was determined by enzymatic cycling assay. Euthyroid T2DM group was divided into 4 subgroups according to TSH levels: G1 (TSH 0.3-0.99 mU/L), G2(TSH 1.0-1.89 mU/L), G3 (TSH 1.9-2.49 mU/L), G4 (TSH 2.5-4.8 mU/L), and Hcy levels were compared among four subgroups. Differences of means between groups were compared by t-test or one-way ANOVA accordingly. The relationships between serum Hcy and other parameters were assessed by simple correlation analysis and logistic regression. Results：Serum Hcy levels was higher in euthyroid T2DM patients than that in controls (［15.4±4.5］ μmol/L vs ［12.9±4.8］ μmol/L, P<0.01). After adjusting for age, gender, and other confounding factors, across euthyroid T2DM subjects Hcy was positively correlated with HOMA-IR (r=0.215) and lgTSH (r=0.235, P<0.05), while negatively correlated with eGFR (r=-0.310, P<0.01). Hcy was not significantly associated with free thyroxine, free triiodothyronine, or lgTSH in normal control group. In euthyroid T2DM group, serum Hcy levels increased parallel with TSH (P<0.05). Based on logistic regression analysis, Hcy was associated with male gender (OR=4.85, 95%CI 1.92-12.23). The risk of HHcy increased significantly in G3 and G4 subgroups compared with G1 subgroups (OR=6.65, 95%CI 1.50-29.54; OR=6.68, 95%CI 1.93-23.14; all P<0.05). Conclusions：Serum homocysteine level is high in euthyroid T2DM patients. Male and a high normal TSH level may be independent risk factors for the presence of HHcy in euthyroid T2DM patients.