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

Sponsor
Attikon Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02509858
Collaborator
(none)
33
Enrollment
3
Arms
76.9
Duration (Months)

Study Details

Study Description

Brief 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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: thyroxine
  • Drug: Placebo
  • Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)
N/A

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 Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Effect of Administration of Small Doses of Thyroxine on Glucose and Lipid Metabolism, at All Stages of Type 2 Diabetes Mellitus.
Study Start Date :
Feb 1, 2009
Actual Primary Completion Date :
Feb 1, 2014
Actual Study Completion Date :
Jul 1, 2015

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: thyroxine in eythyroid diabetics

50 μg of thyroxine once daily, for 2 months.

Drug: thyroxine
treatment with 50μg of thyroxine once daily for two months.
Other Names:
  • T4
  • Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)

    Active Comparator: thyroxine in euthyroid healthy humans

    50 μg of thyroxine once daily, for 2 months.

    Drug: thyroxine
    treatment with 50μg of thyroxine once daily for two months.
    Other Names:
  • T4
  • Other: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)

    Placebo Comparator: placebo in euthyroid diabetics

    50 μg of placebo once daily, for 2 months.

    Drug: 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)

    Outcome Measures

    Primary Outcome Measures

    1. area under the glucose uptake versus time curve-AUC [Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      Muscle glucose uptake following meal ingestion

    Secondary Outcome Measures

    1. Plasma glucose levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    2. Plasma insulin levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    3. Plasma triglyceride levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    4. Plasma total cholesterol levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    5. Plasma LDL-cholesterol levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    6. Plasma HDL-cholesterol levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    7. Plasma Apo-A levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    8. Plasma Apo-B levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    9. Plasma Lp(α) levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    10. Plasma NEFA levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    11. Plasma glycerol levels following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    12. Muscle blood flow following meal ingestion [0, 30, 60, 90, 120, 180, 240, 300 min postmeal]

      area under the plasma concentration versus time curve-AUC

    13. Plasma thyroid hormones [baseline]

      measure of plasma concentration

    14. glucose uptake by peripheral monocytes by the usage of the fluorescent analogue 6-NBDG [baseline to 600 sec]

      area under the curve of 6-NBDG uptake by monocytes under insulin stimulation

    15. % GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin. [baseline]

    16. Number of participants with adverse events [300 min postmeal]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Attikon Hospital

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    VAIA LAMBADIARI, Assistant Professor of of Internal Medicine and Clinical Diabetology , University of Athens, Greece, Attikon Hospital
    ClinicalTrials.gov Identifier:
    NCT02509858
    Other Study ID Numbers:
    • ΒΠΠΚ 50/11-02-09
    First Posted:
    Jul 28, 2015
    Last Update Posted:
    Jul 28, 2015
    Last Verified:
    Jul 1, 2015
    Keywords provided by VAIA LAMBADIARI, Assistant Professor of of Internal Medicine and Clinical Diabetology , University of Athens, Greece, Attikon Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 28, 2015