Thyroid Study Type 2 Diabetes Mellitus (T2DM)
Information source: Maastricht University Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes; Hypothyroidism
Intervention: Euthyrox (levothyroxine) (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Maastricht University Medical Center Overall contact: Evie Broeders, MD, Phone: +31 43 3884254, Email: e.broeders@maastrichtuniversity.nl
Summary
Background of the study:
Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are known to promote weight
loss, which could be beneficial for treating obesity, and type 2 diabetes. Thyroid hormone
treatment stimulates energy expenditure resulting in increased body heat production, in
which brown adipose tissue play an important role. It is hypothesized that thyroid hormones
would induce increased energy expenditure via a process called mitochondrial uncoupling,
thereby creating an inefficient energy status. Indeed, an in vivo study showed a 70%
increased flux through the tricarboxylic acid cycle (TCA) and an unchanged ATP synthesis
rate upon T3 treatment in lean, healthy young men. The disproportionate increase in TCA flux
compared with ATP synthesis suggests increased mitochondrial uncoupling. It is however
unknown whether increased mitochondrial uncoupling would increase fat oxidation and exerts
favorable effects on insulin sensitivity. There is compelling evidence that type 2 diabetic
patients have high levels of fat accumulation in non-adipose tissues, such as skeletal
muscle, heart and liver. Ectopic fat accumulation is related to insulin resistance, however,
why this fat accumulates in peripheral organs is not known. Recently, studies reported
compromised mitochondrial oxidative capacity in type 2 diabetic patients and first-degree
relatives of diabetic patients, suggested to play an important role. Therefore, subjects
suffering from overweight and/or type 2 diabetes with overt hypothyroidism form an
interesting group for examining the metabolic effects of thyroid hormone treatment, as less
is known about the effects of thyroid hormone treatment in these groups.
Objective of the study:
The purpose of this study is to evaluate whether thyroid hormone replacement therapy in type
2 diabetic patients suffering from overt hypothyroidism, will improve muscular mitochondrial
function, lower ectopic fat accumulation in muscle and liver, increase brown adipose tissue
activity and enhance insulin sensitivity.
Study design:
Type 2 diabetic patients diagnosed with hypothyroidism will undergo 3 months of thyroid
hormone replacement therapy (THRT) (Euthyrox®, Merck, Germany). Patients will be
metabolically characterized (such as insulin sensitivity and fat accumulation in peripheral
tissues) before and after this thyroid hormone replacement therapy.
Study population:
17 type 2 diabetic patients diagnosed with overt hypothyroidism (9 from the Netherlands, 8
from Germany which will only do the PET-CT)
Primary study parameters/outcome of the study:
Thyroid hormone-induced change in whole body insulin sensitivity (change in
insulin-stimulated glucose disposal) and muscle mitochondrial function.
Secondary study parameters/outcome of the study (if applicable):
Thyroid hormone-induced change of lipid content in skeletal muscle and liver and brown
adipose tissue activity.
Clinical Details
Official title: Effects of Thyroid Hormone Treatment on Mitochondrial Function, Ectopic Fat Accumulation, Insulin Sensitivity and Brown Adipose Tissue in Type 2 Diabetes Mellitus
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Thyroid hormone-induced change in whole body insulin sensitivity (change in insulin-stimulated glucose disposal) and muscle mitochondrial function
Secondary outcome: Thyroid hormone-induced change of lipid content in skeletal muscle and liver and brown adipose tissue activity
Eligibility
Minimum age: 40 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
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.
- 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.
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 or liver dysfunction (ALT>2. 5 x increased)
- Impaired renal function (creatinine > 120 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 α 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,
thiazolidinediones)
- 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.
- Use of anticoagulants, other than platelet aggregation inhibitors.
- Patients that have donated blood in the past 6 months
Locations and Contacts
Evie Broeders, MD, Phone: +31 43 3884254, Email: e.broeders@maastrichtuniversity.nl
Maastricht University Medical Centre, Maastricht, Limburg 6200MD, Netherlands; Recruiting Evie Broeders, MD, Phone: +31 43 3884254, Email: e.broeders@maastrichtuniversity.nl
Additional Information
Starting date: June 2011
Last updated: May 13, 2013
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