A breakthrough-like effect of metformin reduces peripheral resistance to triiodothyronine in euthyroid, non-insulin-resistant, type 2 diabetic patients

Abstract

Background: Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as wel l. Methods: In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newl y diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructo samine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulat ory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphory lation among normal (5 mM) and high (25 mM) glucose levels with or without metformi n treatment in a human embryonal kidney cell line. Results: Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweig ht, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect. Conclusion: Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

Keywords

• insulin resistance
• metformin
• ratio of t3/t4
• triiodothyronine resistance
• type 2 diabetes mellitus