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

July 27, 2015 updated by: VAIA LAMBADIARI, Attikon Hospital

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

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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: thyroxine in eythyroid diabetics
50 μg of thyroxine once daily, for 2 months.
treatment with 50μg of thyroxine once daily for two months.
Other Names:
  • T4
Active Comparator: thyroxine in euthyroid healthy humans
50 μg of thyroxine once daily, for 2 months.
treatment with 50μg of thyroxine once daily for two months.
Other Names:
  • T4
Placebo Comparator: placebo in euthyroid diabetics
50 μg of placebo once daily, for 2 months.
treatment with 50μg of placebo, once daily, for two months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
area under the glucose uptake versus time curve-AUC
Time Frame: Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Muscle glucose uptake following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma glucose levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma insulin levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma triglyceride levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma total cholesterol levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma LDL-cholesterol levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma HDL-cholesterol levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma Apo-A levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma Apo-B levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma Lp(α) levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma NEFA levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma glycerol levels following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Muscle blood flow following meal ingestion
Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
area under the plasma concentration versus time curve-AUC
0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma thyroid hormones
Time Frame: baseline
measure of plasma concentration
baseline
glucose uptake by peripheral monocytes by the usage of the fluorescent analogue 6-NBDG
Time Frame: baseline to 600 sec
area under the curve of 6-NBDG uptake by monocytes under insulin stimulation
baseline to 600 sec
% GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin.
Time Frame: baseline
baseline
Number of participants with adverse events
Time Frame: 300 min postmeal
300 min postmeal

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: GEORGE DIMITRIADIS, MD, Phd, 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University Medical School, Attikon Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

July 26, 2015

First Submitted That Met QC Criteria

July 27, 2015

First Posted (Estimate)

July 28, 2015

Study Record Updates

Last Update Posted (Estimate)

July 28, 2015

Last Update Submitted That Met QC Criteria

July 27, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diabetes Mellitus

Clinical Trials on thyroxine

3
Subscribe