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

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

Sponsors

Lead sponsor: Attikon Hospital

Source Attikon Hospital
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.

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.

Overall Status Completed
Start Date February 2009
Completion Date July 2015
Primary Completion Date February 2014
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
area under the glucose uptake versus time curve-AUC Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Secondary Outcome
Measure Time Frame
Plasma glucose levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma insulin levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma triglyceride levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma total cholesterol levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma LDL-cholesterol levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma HDL-cholesterol levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma Apo-A levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma Apo-B levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma Lp(α) levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma NEFA levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma glycerol levels following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Muscle blood flow following meal ingestion 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Plasma thyroid hormones baseline
glucose uptake by peripheral monocytes by the usage of the fluorescent analogue 6-NBDG baseline to 600 sec
% GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin. baseline
Number of participants with adverse events 300 min postmeal
Enrollment 33
Condition
Intervention

Intervention type: Drug

Intervention name: thyroxine

Description: treatment with 50μg of thyroxine once daily for two months.

Other name: T4

Intervention type: Drug

Intervention name: Placebo

Description: treatment with 50μg of placebo, once daily, for two months.

Arm group label: placebo in euthyroid diabetics

Intervention type: Other

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

Eligibility

Criteria:

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

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
GEORGE DIMITRIADIS, MD, Phd Study Director 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University Medical School, Attikon Hospital
Verification Date

July 2015

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Attikon Hospital

Investigator full name: VAIA LAMBADIARI

Investigator title: Assistant Professor of of Internal Medicine and Clinical Diabetology , University of Athens, Greece

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: thyroxine in eythyroid diabetics

Arm group type: Active Comparator

Description: 50 μg of thyroxine once daily, for 2 months.

Arm group label: thyroxine in euthyroid healthy humans

Arm group type: Active Comparator

Description: 50 μg of thyroxine once daily, for 2 months.

Arm group label: placebo in euthyroid diabetics

Arm group type: Placebo Comparator

Description: 50 μg of placebo once daily, for 2 months.

Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov