Subclinical hypothyroidism contributes to poor glycemic control in patients with type 2 diabetes mellitus, and ellagic acid attenuates methimazole-induced abnormal glucose metabolism in mice model

Abstract

Subclinical hypothyroidism (SCH) as mild thyroid disorder or comorbidity in patients with endocrine disorders is closely related with insulin resistance (IR) and poor glycemic control. The present study attempted to investigate the effect of SCH on IR and glycemic control in patients with type 2 diabetes mellitus (T2DM). In addition, the effects of ellagic acid (EA) on SCH C57BL/6J and db/db mice were also investigated to explore potential therapeutic drug against SCH-induced abnormal glucose metabolism. T2DM patients were recruited in our study and categorized into two groups according to thyroid stimulating hormone (TSH) value: T2DM without SCH group (TSH ≤4 μIU/ml; n = 30) and T2DM with SCH group (TSH >4μIU/ml; n = 60). Methimazole (MMI; 0.08 mg kg^-1 day^-1 ) was intragastrically administrated for 12 weeks to establish SCH in C57BL/6J and db/db mice. Compared with T2DM patients without SCH, poor glycemic and cholesterol control were emerged in T2DM patients with SCH and that were prominent in patients with TSH more than 10 μIU/ml. In addition, a significant positive correlation between serum TSH and fasting plasma-glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), or glycated hemoglobin (HbA1c) was observed in T2DM patients with SCH. Moreover, abnormal glucose metabolism in C57BL/6J and db/db mice with SCH has been attenuated by EA administration. Our findings provided data regarding the positive correlation between high TSH level with poor glycemic control in T2DM patients with SCH. EA might be a supportive strategy for preventing SCH-induced abnormal glucose metabolism. PRACTICAL APPLICATIONS: Subclinical hypothyroidism (SCH) is a potential risk factor associated with abnormal glucose metabolism in patients with type 2 diabetes mellitus (T2DM). A clinical theory of a positive correlation between high TSH level and poor glycemic control was validated in type 2 diabetes mellitus patients and mouse models. Ellagic acid (EA) might be a supportive strategy for preventing SCH-induced abnormal glucose metabolism that provided a treatment option in T2DM patients with subclinical hypothyroidism in clinical practice.

Keywords: ellagic acid; glucose metabolism disorders; hypothyroidism; insulin resistance; type 2 diabetes mellitus.