Insulin resistance obesity
Conditions
Interventions
All subjects will undergo an intervention consisting of three capsules per day,
during 8 continuous weeks. One group will receive a placebo treatment, another
a dosage of 25 mg pyridoxamine per day,
Sponsors
Universiteit Maastricht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Abdominal obesity: Waist circumference for men should be above 102 cm, for women above 88 cm. - Caucasian (because of skin fluorescence and capillary microscopy measurements) - Aged 18-75 years
Exclusion criteria
Exclusion criteria: - Diabetes mellitus (i.e. using anti-diabetic medication, fasting glucose >7.0 mmol/L, HbA1c >6.5%). - Active or history of cardiovascular disease (e.g. stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death) - Hyperlipidemia (defined as serum total cholesterol > 8 mmol/L or TG > 4 mmol/L) - Smoking will be allowed. Smokers will be excluded only if they smoke >10 cigarettes per day. - High alcohol usage (>4 U/day) or drug abuse - Use of medication known to influence glucose metabolism or vascular function (e.g. glucocorticosteroids, NSAID's) - Exclusion of higher grade hypertension (> 179 mmHg SBP and/or > 109 mmHg DBP) in order not to expose subjects to unnecessary risks. Medication is allowed. - Known allergic reaction to ultrasound contrast-agent - Pulmonary or inflammatory disease - Kidney failure or electrolyte disorders - Use of dietary supplements or an investigational product within the previous month - Unstable body weight (no drastic changes in life style before or during the intervention are allowed, this means no weight gain or loss >3 kg in the last two months) - Pregnancy or lactation - No change in use of oral anticonceptiva or IUD (12 weeks prior of during the intervention) - Unwillingness to give up being a blood donor (or having donated blood) from 8 weeks prior to the start of the study and during the study - Insufficient knowledge of the Dutch language
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measurements at baseline and during the follow-up study day (after the intervention) will be compared to analyse the effect between the study groups. The main study parameters are the evaluation of vascular (dys)function, insulin sensitivity, and adipokine levels. These parameters will be investigated by a series of predominant micro- and macrovascular measurements, a hyperinsulinemic euglycemic clamp, an OGTT, AGE skin readings and blood plasma analysis for several inflammation, endothelial, and adipokine markers, as well as AGE levels. Microvascular tests include skin capillary videomicroscopy, skin flowmotion and heating-response (LDF), sublingual imaging of the endothelial glycocalyx, and contrast-enhanced ultrasound of the skeletal muscle microcirculation. All microcirculation measurements will be performed before and during the hyperinsulinemic euglycemic clamp to study insulin-induced microvascular function. Macrovascular tests include carotid distensibility, pulse wave analysis, pulse wave velocity, brachial artery flow mediated dilatation (FMD). Primary parameters: 1) Micro- and macrovascular function by means of skeletal muscle contrast-enhanced ultrasound (CEUS) measurements and flow mediated dilation (FMD) 2) Whole body insulin sensitivity using a hyperinsulinemic, euglycemic clamp | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Micro- and macrovascular function by means of skin capillary videomicroscopy, skin laser doppler flowmetry (LDF), and arterial stiffness (pulse wave velocity and local stiffness). 2) Glucose metabolism and B-cell function using an OGTT 3) AGE measurements in blood plasma and skin (skin autofluorescence (SAF)). 4) Adipokine, endothelial function marker, and inflammation marker measurements in plasma. | — |
Countries
Netherlands
Outcome results
None listed