Obesity, Abdominal
Conditions
Brief 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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTPlacebo
Capsule without cafestol twice daily
DIETARY_SUPPLEMENTCafestol
Capsule with 6 mg cafestol twice daily
Sponsors
Aarhus University Hospital
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L) | 220, 230 and 240 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose. | 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. |
| Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L) | 100, 110 and 120 minutes after test-start. Comparison between pre-intervention and end-intervention steady state plasma glucose. | 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. |
| Area under the curve for glucose during mixed meal test (mmol/L*min) | -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 glucose during a mixed meal test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve for triglycerides during mixed meal test (mmol/L*min) | -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 triglycerides during a mixed meal test. |
| Glycated hemoglobin (HbA1c) (mmol/mol) | 12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels. | Glycated hemoglobin (HbA1c) (mmol/mol) |
| Visceral fat content (ml) | 12-week change. Comparison between pre-intervention scan and end-intervention scan. | Measured with dixon-sequences scanning the abdomen |
| Liver fat content (%) | 12-week change. Comparison between pre-intervention scan and end-intervention scan. | Measured with dixon-sequences scanning the abdomen and MR-Spectroscopy. |
| One-week continuous glucose measurement | 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. | One-week continuous glucose measurement data. |
| Blood pressure (mmHg) | 12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure. | 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. |
| Food consumption in kilocalories (kcal) | 12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption. | Food consumption is registered for 72-hours prior to study day 1 and 3. Food consumption is measured in kilocalories (kcal). |
| Subcutaneous fat content (ml) | 12-week change. Comparison between pre-intervention scan and end-intervention scan. | Measured with dixon-sequences scanning the abdomen |
| Area under the curve for insulin during mixed meal test (pmol/L*min) | -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 a mixed meal test. |
| Area under the curve for glucagon during mixed meal test (pmol/L*min) | -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 a mixed meal test. |
Other
| Measure | Time frame |
|---|---|
| Fasting procollagen type 1 N-terminal propeptide (µg/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting parathyroid hormone (pmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting vitamin D (nmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting ionized calcium (mmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting interleukin 8 (pg/ml) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting interleukin 1 (pg/ml) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting glucagon-like peptide-2 (pmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting growth/differentiation factor 15 (ng/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting tumor necrosis factor (TNFα) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting Homeostatic Model Assessment for Insulin Resistance by C-peptide (arbitrary unit). | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting gastric inhibitory polypeptide (pmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting glucose (mmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting insulin (pmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting total cholesterol (mmol/l), | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting HDL (mmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting monocyte chemoattractant protein-1 (pg/ml) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting LDL (mmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting triglycerides (mmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting thyroid-stimulating hormone (international unit (IU)/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting alanine aminotransferase (unit(U)/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting high sensitivity c reactive protein (mg/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting alpha-hydroxybutyrate (mmol/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
| Fasting C-terminal telopeptide (µg/l) | Measured on study day 1 and 3. 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples. |
Countries
Denmark
Outcome results
None listed