The Effect of Administration of Small Doses of Thyroxine on Glucose and Lipid Metabolism, in Type 2 Diabetes Mellitus.

Attikon University Hospital

Status: Completed

Conditions: Diabetes Mellitus

Treatments: Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein); Drug: Placebo; Drug: thyroxine

Study type: Interventional

Funder types: Other

Identifiers

NCT02509858

ΒΠΠΚ 50/11-02-09

Details and patient eligibility

About

We investigated the effect of the administration of small doses of thyroxine to healthy humans and patients with type 2 diabetes on postprandial forearm muscle glucose uptake, insulin sensitivity indices, lipid metabolism, in vitro glucose uptake and GLUT4 recruitment in the plasma membrane of monocytes.

Full description

The present open-labeled, randomized and placebo-controlled study was undertaken in euthyroid type 2 diabetic patients and healthy humans, to examine the effect of administration of small doses of thyroxine within the euthyroid range, on muscle glucose disposal, postprandial insulin sensitivity, lipid metabolism, in vitro glucose uptake and GLUT4 recruitment in the plasma membrane of monocytes.This was investigated with the arteriovenous-difference technique after the consumption of a mixed meal and the in vitro study of a glucose analogue(6-NBDG) uptake by the peripheral monocytes.

Subjects and Methods: Eleven euthyroid, treatment naive, type-2 diabetic patients with a micronodular texture of the thyroid gland and eleven healthy euthyroid subjects, were studied before and after administration of 50 μg of thyroxine once daily for 2 months. In parallel, a placebo group was also studied. Eleven euthyroid treatment-naïve subjects with type 2 diabetes and a micronodular texture of the thyroid gland, matched for age, sex, BMI, and basal thyroid function, were studied before and after administration of a placebo, once daily for 2 months.

Experimental protocol: All subjects were admitted to the hospital at 0700 h after an overnight fast and had the radial artery (A) and a forearm deep vein (V) catheterized. A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein) was given at least 1 h after catheter insertion and was consumed within 20 min. Blood samples were drawn from both sites before the meal (at -30 and 0 min) and at 30- to 60-min intervals for 300 min thereafter for measurements of thyroid hormones,glucose, total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides, Apolipoprotein A1, Apolipoprotein BII and Lp(a).Forearm blood flow was measured with strain-gauge plethysmography. After the first meal tolerance test, treatment with 50μg of thyroxine or placebo, once daily, was initiated for a 2-month period. Then a second identical test was repeated. Special care was taken in order to avoid the induction of subclinical hyperthyroidism, that is suppression of TSH below 0.27 μU/ml, as it has recently been shown that the latter is also an insulin-resistant condition.

Enrollment: 33 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy or treatment naive type 2 diabetes euthyroid subjects, with a micronodular texture of the thyroid gland.
• Recreationally active
• With stable body weight and diet during the last two months.

Exclusion criteria

• Any systemic disease(besides glucose abnormalities)
• Any medication therapy
• Diabetic complications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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33 participants in 3 patient groups, including a placebo group

thyroxine in eythyroid diabetics

Active Comparator group

Description:

50 μg of thyroxine once daily, for 2 months.

Treatment:

Drug: thyroxine

Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)

thyroxine in euthyroid healthy humans

Active Comparator group

Description:

50 μg of thyroxine once daily, for 2 months.

Treatment:

Drug: thyroxine

Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)

placebo in euthyroid diabetics

Placebo Comparator group

Description:

50 μg of placebo once daily, for 2 months.

Treatment:

Drug: Placebo

Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)