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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
40
Steno Diabetes Center Aarhus
Aarhus, Aarhus N, Denmark
Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)
Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 milliunits (mU) insulin / m2 • minute, and 50 mg glucose / m2 • minute. At time-point 120 minutes, infusion speeds were increased to to 32 mU insulin / m2 • minute and 267 mg glucose / m2 • minute.
Time frame: 220, 230 and 240 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.
Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)
Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 mU insulin / m2 • minute, and 50 mg glucose / m2 • min.
Time frame: 100, 110 and 120 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose.
Area under the curve for glucose during mixed meal test (mmol/L*min)
Area under the curve for glucose during a mixed meal test.
Time frame: -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves.
Area under the curve for insulin during mixed meal test (pmol/L*min)
Area under the curve for insulin during a mixed meal test.
Time frame: -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves.
Area under the curve for glucagon during mixed meal test (pmol/L*min)
Area under the curve for glucagon during a mixed meal test.
Time frame: -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves.
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Area under the curve for triglycerides during mixed meal test (mmol/L*min)
Area under the curve for triglycerides during a mixed meal test.
Time frame: -15 to 240 minutes from ingestion of standardized meal at time point 0 minutes. Comparison between pre-intervention and end-intervention area under the curves.
Glycated hemoglobin (HbA1c) (mmol/mol)
Glycated hemoglobin (HbA1c) (mmol/mol)
Time frame: 12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels.
Liver fat content (%)
Measured with dixon-sequences scanning the abdomen and MR-Spectroscopy.
Time frame: 12-week change. Comparison between pre-intervention scan and end-intervention scan.
Visceral fat content (ml)
Measured with dixon-sequences scanning the abdomen
Time frame: 12-week change. Comparison between pre-intervention scan and end-intervention scan.
Subcutaneous fat content (ml)
Measured with dixon-sequences scanning the abdomen
Time frame: 12-week change. Comparison between pre-intervention scan and end-intervention scan.
One-week continuous glucose measurement
One-week continuous glucose measurement data.
Time frame: Average glucose measured every 15 minutes for one week prior to study day 1 and 3. 12-week change. Comparison between pre-intervention measurement and end-intervention measurement.
Blood pressure (mmHg)
Average daytime and night-time ambulatory blood pressure. 24-hour ambulatory blood pressure measurement, measured every 20 minutes during daytime and every 30 minutes during nighttime.
Time frame: 12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure.
Food consumption in kilocalories (kcal)
Food consumption is registered for 72-hours prior to study day 1 and 3. Food consumption is measured in kilocalories (kcal).
Time frame: 12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption.