long-term metabolic effects of cafestol

Conditions: Obesity, Abdominal

Summary: twelve-week double-blinded, placebo-controlled, parallel intervention study on 40 participants with a large waist circumference who will ingest cafestol or placebo capsules twice daily. insulin resistance is measured before and after the twelve-week intervention.

participants are randomly allocated to the cafestol intervention group or placebo group. before and after the twelve-week intervention the participants partake in: * a modified two-stage insulin suppression test to determine insulin mediated glucose uptake. fasting participants receive body-surface-area-adjusted octreotide, insulin and glucose infusions for 240 minutes. octreotide is infused with the same rate throughout the test. insulin and glucose infusions are slow for the initial 120-minute stage and increased the final 120-minute stage, simulating fasting and post-postprandial conditions, respectively. steady state measurements of plasma glucose are acquired the final 30 minutes of each stage, at time points 100, 110, 120, 220, 230 and 240 minutes. * a mixed meal test. fasting participants consume 75 g. white bread, 10 g. butter, 30 g. cheese and 200 ml. orange juice. blood samples are drawn at time points -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for glucose-, insulin-, glucagon- and triglyceride measurements. * a magnetic resonance imaging (mri) scan. participants undergo dixon-sequences scanning the abdomen, assessing visceral and sub-cutaneous fat volume and liver fat content. magnetic resonance (mr) spectroscopy is also used to determine fat percentage of the liver. * 24-hour ambulatory blood pressure measurement, every 20 minutes during daytime and every 30 minutes during nighttime. * 1-week continuous glucose measurement using blinded continuous glucose monitor/sensor on upper arm. * fecal and urine sampling * 72-hour food-diary * fasting blood samples: * insulin, c-peptide, hba1c and glucose * total cholesterol, high density lipoprotein (hdl), low density lipoprotein (ldl) and triglycerides * thyroid-stimulating hormone (tsh) * alanine aminotransferase, creatinine, sodium and potassium * high sensitivity c reactive protein (crp) and alpha-hydroxybutyrate * c-terminal telopeptide (ctx) and procollagen type 1 n-terminal propeptide (p1np) * parathyroid hormone (pth), vitamin d and ionized calcium * monocyte chemoattractant protein-1 (mcp-1) * interleukin 1 \& 8 (il-1α, il-1β, il-8) * gastric inhibitory polypeptide (gip), glucagon-like peptide-1 (glp-1) and glucagon- like peptide-2 (glp-2) * growth/differentiation factor 15 (gdf-15) * tumor necrosis factor (tnfα) * fasting assessment of insulin resistance (homeostatic model assessment for insulin resistance by c-peptide). pre-intervention and end-intervention test results will be compared using repeated-measures anova / mixed models.

Eligibility criteria:
inclusion criteria: waist circumference \> 102 cm (men) / 88 cm (women) exclusion criteria: * type 2 diabetes (hba1c \> 48 mmol/mol) or in treatment with antidiabetic drugs * pregnancy * planned pregnancy * breastfeeding * significant comorbidity expected to unable the subject from completing visits