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.
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.