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

Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02509858
• Other study ID #: ???? 50/11-02-09
• Status: Completed
• Phase: N/A
• First received: July 26, 2015
• Last updated: July 27, 2015
• Start date: February 2009
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: Attikon Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: July 2015
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• thyroxine
treatment with 50µg of thyroxine once daily for two months.
• Placebo
treatment with 50µg of placebo, once daily, for two months.

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Attikon Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	area under the glucose uptake versus time curve-AUC	Muscle glucose uptake following meal ingestion	Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma glucose levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma insulin levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma triglyceride levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma total cholesterol levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma LDL-cholesterol levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma HDL-cholesterol levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma Apo-A levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma Apo-B levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma Lp(a) levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma NEFA levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma glycerol levels following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Muscle blood flow following meal ingestion	area under the plasma concentration versus time curve-AUC	0, 30, 60, 90, 120, 180, 240, 300 min postmeal	No
Secondary	Plasma thyroid hormones	measure of plasma concentration	baseline	No
Secondary	glucose uptake by peripheral monocytes by the usage of the fluorescent analogue 6-NBDG	area under the curve of 6-NBDG uptake by monocytes under insulin stimulation	baseline to 600 sec	No
Secondary	% GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin.		baseline	No
Secondary	Number of participants with adverse events		300 min postmeal	Yes