Effects of thyroid hormone treatment on mitochondrial function, ectopic fat accumulation, insulin sensitivity and brown adipose tissue in type 2 diabetes mellitus

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 33

Inclusion Criteria

- Male or postmenopausal females
- Age 40-65 years
- Body mass index (BMI) < 40 and > 27 kg/m2
- Stable dietary habits (no weight loss/gain >3 kg in the last 6 months)
- Stable physical activity levels for at least six months ;- Newly diagnosed hypothyroid, non-insulin dependent type 2 diabetic patients having TSH values higher then > 4.0 mU/l and lowered concentrations of free T4 < 8.0 pmol/l
- Inclusion of patients who developed overt hypothyroidism due to subtotal thyroidectomy (strumectomy), except for those who underwent thyroidectomy because of thyroid carcinoma,
- Type 2 diabetic patients using sulphonylurea and or metformin therapy for at least six months with a constant dose for at least two months
- Hypothyroid diabetic patients due to Hashimoto disease (TPO > 100 IE/ml; Tg > 344 IE/ml), should have no auto-antibodies against glutamic acid decarboxylase (GAD), IA-2 and insulin to exclude type 2 polyglandular autoimmune syndrome (PGAII) (to exclude type 1 diabetes).
- Type 2 diabetic patients should have a HbA1c level < 8.0%
- Type 2 diabetic patients will be included when having no diabetes-related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy. ;Inclusion criteria for non-diabetic de novo hypothyroid patientsMale or postmenopausal females
- Age 18-65 years
- Body mass index (BMI) < 40 and > 27 kg/m2
- Stable dietary habits (no weight loss/gain >3 kg in the last 6 months)
- Stable physical activity levels for at least six months ;- Newly diagnosed hypothyroid, patients having TSH values higher then > 4.0 mU/l (and lowered concentrations of free T4 < 8.0 pmol/l)

Exclusion Criteria

- Unstable body weight
- Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study
- Medical history including active cardiovascular disease, i.e. history of coronary artery disease (i.e. history of angina pectoris, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting) or cardiac arrhythmias.
- Liver disease of liver dysfunction (ALT>2.5 x increased)
- Impaired renalfunction (Kreat >100 umol/L)
- Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg
- Hb <7.4 mmol/l (12 g/dl) in women, and <8.1 mmol/l (13 g/dl) in men
- Abuse of drugs and/or alcohol
- Contraindications for MRI scanning (please see appendix III: MRI contraindication questionnaire);- Patients with history of thyroid cancer
- patients using a and/or β blockers
- Severe diabetes which requires application of insulin or patients with diabetes-related complications
- History of psychiatric disease
- Diabetes related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy.
- Use of medications known to interfere with glucose homeostasis (i.e. corticosteroids, thiazolidendiones)
- Hypothyroid diabetic patients due to Hashimoto disease with positive test values for auto-antibodies against GAD, IA-2 and insulin to exclude type 1 diabetes

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>For the diabetes-group: Thyroidhormone induced changes in insulin sensitivity<br /><br>and mitochondrial function of skeletal muscle.<br /><br>For the non-diabetic group: Thyroidhormone induced changes is brown adipose<br /><br>tissue activity. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Diabetics: Thyroid hormone-induced change of lipid content in skeletal muscle<br /><br>and liver and brown adipose tissue activity.<br /><br>Non-diabetics: thyroid hormone induced changes in energy expenditure. </p><br>