Pioglitazone Influence of triglyceRide Accumulation in the Myocardium In Diabetes

Recruitment & Eligibility

Status: Completed

Sex: Male

Target Recruitment: 90

Inclusion Criteria

Type two diabetes patients:
1. Type two diabetes diagnosed male patients aged 45 to 65 years (diagnosed according to World Health Organisation [WHO] criteria)
2. Treated by monotherapy of sulfanylurea (i.e. unchanged during more than 30 days prior to inclusion)
3. At least three months stable HbA1c (less than 8.5%) under this therapy
4. Sitting blood pressure less than 150/85 mmHg with or without anti-hypertensive drugs
5. Body Mass Index (BMI) less than 32 kg/m^2

Healthy volunteers:
1. Healthy male subjects, 45 to 65 years
2. Normal sitting blood pressure less than 150/85 mmHg
3. BMI less than 32 kg/m^2
4. Normal glucose tolerance as assessed by 75 g oral glucose tolerance test

Exclusion Criteria

Type two diabetes patients:
1. Coronary Artery Disease (CAD)
2. Active malignant disease
3. Impaired renal function (serum creatinine more than 176 mmol/l)
4. Weight greater than or equal to 45 kg (because of 11C-palmitate tracer)
5. Anti-coagulant therapy
6. Severe obstructive lung disease
7. Hereditary lipoprotein disease
8. Impaired hepatic function (defined as Alanine aminotransferase [ALT] more than three Upper Limit of Normal [ULN]) or a history of liver disease
9. Inability to understand study information
10. Inability/unwillingness to sign informed consent
11. Substance abuse
12. Familial polyposis coli
13. Less than three months after participation in other clinical trials or other research projects, whereby radiation is used
14. Haemoglobin less than 8 mmol/l
15. Metal implants and claustrophobia
16. Incompatible with Cardiovascular Magnetic Resonance (CMR)
17. Congestive heart failure (New York Heart Association [NYHA] functional score more than one)
18. Atrial fibrillation or history of sustained ventricular tachycardia
19. Stroke within six months prior to enrolment
20. Microvascular complications including:
a. diabetic nephropathy
b. proliferative retinopathy
c. symptomatic macrovascular complications, and/or
d. (autonomic) neuropathy, except for background diabetic retinopathy, leg ulcers, gangrene, hypersensibility to study medication, current use of Thiazolidinediones (TZD)/fibrates

Healthy volunteers:
1. History or current cardiovascular disease
2. Dyslipidemia, requiring pharmacological treatment according to the Dutch Cholesterol Consensus 1998

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Changes in cardiac function and metabolism following treatment with PPARg agonist versus current state of the art therapy, metformin.

Secondary Outcome Measures

Name	Time	Method
1. Glucose and Free Fatty Acid (FFA) uptake by adipose tissue and skeletal muscle<br>2. Cardiac High-Energy-Phosphate (HEP) metabolism<br>3. Haemodynamic and vascular parameters body composition (Body Mass Index [BMI], waist, adipose tissue distribution, including liver fat content, body fat percentage and fluid retention)<br>4. Plasma parameters of glycemic control and lipoprotein metabolism<br>5. Circulating levels of markers of inflammation, coagulation activation, fibrinolysis and endothelial functions<br>6. Whole-body insulin sensitivity (by clamp)