The Effect of Administration of Small Doses of Thyroxine on Glucose and Lipid Metabolism, at All Stages of Type 2 Diabetes Mellitus.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 主要终点
- area under the glucose uptake versus time curve-AUC
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •Any systemic disease(besides glucose abnormalities)
- •Any medication therapy
- •Diabetic complications
研究组 & 干预措施
thyroxine in euthyroid healthy humans
50 μg of thyroxine once daily, for 2 months.
干预措施: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein) (Other)
thyroxine in eythyroid diabetics
50 μg of thyroxine once daily, for 2 months.
干预措施: thyroxine (Drug)
thyroxine in eythyroid diabetics
50 μg of thyroxine once daily, for 2 months.
干预措施: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein) (Other)
thyroxine in euthyroid healthy humans
50 μg of thyroxine once daily, for 2 months.
干预措施: thyroxine (Drug)
placebo in euthyroid diabetics
50 μg of placebo once daily, for 2 months.
干预措施: Placebo (Drug)
placebo in euthyroid diabetics
50 μg of placebo once daily, for 2 months.
干预措施: A meal (730kcal, 50%carbohydrate, of which 38% was starch, 40% fat, and 10% protein) (Other)
结局指标
主要结局
area under the glucose uptake versus time curve-AUC
时间窗: Time Frame: 0, 30, 60, 90, 120, 180, 240, 300 min postmeal
Muscle glucose uptake following meal ingestion
次要结局
- 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 LDL-cholesterol 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 thyroid hormones(baseline)
- Plasma glycerol 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 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 NEFA levels following meal ingestion(0, 30, 60, 90, 120, 180, 240, 300 min postmeal)
- % GLUT4 increment from baseline (0mU/l) to maximal concentration (200mU/l) of insulin.(baseline)
- Plasma Apo-B 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)
- glucose uptake by peripheral monocytes by the usage of the fluorescent analogue 6-NBDG(baseline to 600 sec)
- Number of participants with adverse events(300 min postmeal)
研究者
VAIA LAMBADIARI
Assistant Professor of of Internal Medicine and Clinical Diabetology , University of Athens, Greece
Attikon Hospital