Diabetes Mellitus
Conditions
Keywords
Diabetes mellitus, thyroxine
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.
Interventions
DRUGthyroxine
treatment with 50μg of thyroxine once daily for two months.
DRUGPlacebo
treatment with 50μg of placebo, once daily, for two months.
OTHERA meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein)
Sponsors
Attikon Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events | 300 min postmeal | — |
| 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 |
| 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 |
| 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 |
| 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 |
| Plasma thyroid hormones | baseline | measure of plasma concentration |
| 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 |
| % GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin. | baseline | — |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Outcome results
None listed