Does the Bioactive Substance in Coffee, Cafestol, Have Preventive Properties on Type-2-diabetes? (Long-term Substudy)
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)
研究概览
简要总结
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.
详细描述
Participants are randomly allocated to the cafestol intervention group or placebo group. Before and after the twelve-week intervention the participants partake in:
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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.
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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.
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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.
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24-hour ambulatory blood pressure measurement, every 20 minutes during daytime and every 30 minutes during nighttime.
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1-week continuous glucose measurement using blinded continuous glucose monitor/sensor on upper arm.
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Fecal and urine sampling
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72-hour food-diary
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Fasting blood samples:
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Insulin, c-peptide, HbA1c and glucose
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Total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides
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Thyroid-stimulating hormone (TSH)
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Alanine aminotransferase, creatinine, sodium and potassium
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High sensitivity C reactive protein (CRP) and alpha-hydroxybutyrate
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C-terminal telopeptide (CTX) and Procollagen type 1 N-terminal propeptide (P1NP)
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Parathyroid hormone (PTH), Vitamin D and Ionized calcium
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Monocyte Chemoattractant Protein-1 (MCP-1)
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Interleukin 1 & 8 (IL-1α, IL-1β, IL-8)
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Gastric inhibitory polypeptide (GIP), Glucagon-like peptide-1 (GLP-1) and Glucagon- like peptide-2 (GLP-2)
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Growth/differentiation factor 15 (GDF-15)
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Tumor necrosis factor (TNFα)
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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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Waist circumference > 102 cm (men) / 88 cm (women)
排除标准
- •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
研究组 & 干预措施
Cafestol
Participants in this arm ingest 6 mg cafestol capsules twice daily with breakfast and dinner.
干预措施: Cafestol (Dietary Supplement)
Placebo
Participants in this arm ingest placebo capsules twice daily with breakfast and dinner.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)
时间窗: 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)
时间窗: 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)
时间窗: -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.
次要结局
- 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 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 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.)
- Glycated hemoglobin (HbA1c) (mmol/mol)(12-week change. Comparison between pre-intervention and end-intervention glycated hemoglobin levels.)
- Liver fat content (%)(12-week change. Comparison between pre-intervention scan and end-intervention scan.)
- Visceral fat content (ml)(12-week change. Comparison between pre-intervention scan and end-intervention scan.)
- Subcutaneous fat content (ml)(12-week change. Comparison between pre-intervention scan and end-intervention scan.)
- 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.)
- Blood pressure (mmHg)(12-week change. Comparison between pre-intervention average ambulatory blood pressure and end-intervention average ambulatory blood pressure.)
- Food consumption in kilocalories (kcal)(12-week change. Comparison between pre-intervention food consumption and end-intervention food consumption.)