Vaia Lambadiari, Filio Spanoudi, Eirini Maratou, Evangelina Vassilatou, Erifili Hatziagelaki, Panagiota Mitrou, George Matsangouras, George Dimitriadis
Purpose: Variation of plasma thyroid hormone levels influences insulin sensitivity and peripheral glucose disposal. High thyroxin dose administration to healthy humans induces insulin resistance, whereas moderate doses increase peripheral glucose disposal. An open-labeled, randomized and placebo-controlled intervention was performed in euthyroid type 2-diabetic patients, to examine the effect of a small thyroxin dose within the euthyroid range on postprandial forearm muscle glucose uptake, insulin sensitivity, in vitro glucose uptake and GLUT4 recruitment in the plasma membrane of monocytes. Methods: A meal was given to eleven euthyroid, treatment-naive, type-2 diabetic patients (aged 43 ± 3.8 yrs, BMI 27.48 ± 1.39 kg/m2, T3 119 ± 5.7 ng/dl, T4 8,13 ± 0.46 μg/dl, TSH 1.51 ± 0.14 μU/ml, FT4 1.272 ± 0.047 ng/dl) before and after administration of 50 μg of thyroxin once daily for 2 months. Similarly, a placebo was given to eleven age, sex and BMI-matched euthyroid, type-2 diabetic patients. Blood was drawn for 300 min from a forearm deep vein and the radial artery for measurements of glucose, insulin, and GLUT4 abundance in peripheral monocytes. Forearm blood flow (BF) was measured with strain-gauge-plethysmography. Forearm glucose-uptake, and insulin sensitivity were assessed. After the first meal-tolerance-test, daily treatment with 50 μg of thyroxin or placebo was initiated for a 2-month period. Then a second identical test was repeated. Results: TSH, glucose, insulin levels and HbA1c reduced significantly in the treatment group. Peak-baseline BF and Glucose-uptake (AUC0-300 min) increased significantly (1.685 ± 0.3 vs. 3.07 ± 0.15 ml/min per 100 cc tissue, p=0.0018) and (587 ± 68 vs. 1015 ± 131 μmol per 100 cc tissue, p=0.0051), respectively. All insulin-sensitivity indices improved post-treatment. Glucose uptake and GLUT4 abundance in monocytes also improved. The placebo group exhibited no change in all variables. Conclusion: Administration of small, subthyrotoxic doses of thyroxin to euthyroid diabetic patients improves peripheral glucose disposal, blood flow responses and overall insulin sensitivity. This could be of therapeutic importance by reducing the burden of hyperglycaemia and possibly the long term complications of diabetes.