Ciprofibrate and Pre-diabetes

Objectives: The main objective of the study is to investigate whether ciprofibrate treatment can improve myocardial insulin sensitivity in subjects with IGM. As secondary objectives we want to investigate whether ciprofibrate treatment also improves diastolic and myocardial mitochondrial function and decreases intracardiomyocellular lipid content. Futhermore, since ciprofibrate could also affect cardiac metabolism indirectly, we want to investigate the effect of ciprofibrate on skeletal and hepatic glucose uptake, hepatic lipid storage and composition.

Study design: In a randomized, double-blind, cross-over design, the effects of ciprofibrate supplementation on myocardial insulin sensitivity will be compared to placebo in humans with IGM.

Study population: Twelve male, overweight (BMI > 27 kg/m2), insulin-resistant subjects, aged between 40 and 70 years, without cardiac disease, will participate in this study.

Intervention: Subjects will be asked to take one pill of ciprofibrate 100mg, or placebo, once daily (at dinner), for 35 days.

Main study parameters/endpoints: The main study endpoint is the difference in myocardial insulin sensitivity (measurement of glucose uptake using radio-active labeled 18F-FDG tracer in PET-MRI) after ciprofibrate administration compared to the placebo trial.

Inclusion criteria

• Race: caucasian
• Sex: male
• Age: 40-70 years
• BMI: 27-35 kg/m2
• Stable dietary habits: no weight gain or loss > 5kg in the last three months
• Insulin resistant: glucose clearance rate below < 360 ml/kg/min, as determined using OGIS120

Exclusion criteria

• Patients with a cardiac disease or with instable angina
• Patients with hepatic or renal failure
• Haemoglobin <7.8 mmol/l
• In case of an abnormal ECG in rest: this will be discussed with the responsible medical doctor
• HbA1c > 6.5%
• Diagnosed with type 1 or type 2 diabetes mellitus
• Patients with alcohol abuse
• Use of a fibrate
• Medication use known to interfere with glucose homeostasis/metabolism
• Use of anti-coagulants, excluding platelet aggregation inhibitors
• Subjects who do not want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed, cannot participate in the study.
• Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention.
• Participation in another biomedical study within 1 month before the first screening visit
• Any condition, disease or abnormal laboratory test result that, in the opinion of the Investigator, would interfere with the study outcome, affect trial participation or put the subject at undue risk
• Any contra-indication to MRI scanning. These contra-indications include patients with following devices:

• Electronic implants such as pacemakers or defibrillator or neurostimulator
• Central nervous system aneurysm clip
• Some hearing aids (such as cochlear implant) and artificial (heart) valves which are contraindicated for MRS
• Iron containing corpora aliena in the eye or brains
• Claustrophobia
• Participation in earlier research or medical examinations in the past 3 months that included PET/MRI scanning