Long-term Metabolic Effects of Cafestol

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.