Clinical trial NCT02509858: The Effect of Administration of Small Doses of Thyroxine on Glucose and Lipid Metabolism, in Type 2 Diabetes Mellitus.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Keywords: Diabetes mellitus, thyroxine
Lead sponsor: Attikon Hospital
Sponsor class: OTHER
First posted: 2015-07-28
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: area under the glucose uptake versus time curve-AUC
timeFrame: Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Secondary outcomes:
measure: Plasma glucose levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma insulin levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma triglyceride levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma total cholesterol levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma LDL-cholesterol levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma HDL-cholesterol levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma Apo-A levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma Apo-B levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma Lp(α) levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma NEFA levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma glycerol levels following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Muscle blood flow following meal ingestion
timeFrame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
measure: Plasma thyroid hormones
timeFrame: baseline
measure: glucose uptake by peripheral monocytes by the usage of the fluorescent analogue 6-NBDG
timeFrame: baseline to 600 sec
measure: % GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin.
timeFrame: baseline
measure: Number of participants with adverse events
timeFrame: 300 min postmeal
Other outcomes:
Locations:
Study officials:
affiliation: 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University Medical School, Attikon Hospital
name: GEORGE DIMITRIADIS, MD, Phd
role: STUDY_DIRECTOR
References: