Effect of Moderate Alcohol Consumption on Cephalic Phase Reflex and Gene Expression of Adipose Tissue in Postmenopausal Women
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Gene expression profiles in adipose tissue
研究概览
简要总结
Moderate alcohol consumption has consistently been associated with lowered risk of developing type two diabetes mellitus compared to abstainers and heavy drinkers. However, the underlying mechanism for the lower risk of type two diabetes is not clear.
Hypothesis: moderate alcohol consumption for four weeks changes gene expression pathways of inflammatory status, insulin sensitivity and lipid and carbohydrate metabolism in adipose tissue in both lean and obese postmenopausal women.
Hypothesis: Oral sensory stimulation by means of alcohol in the oral cavity will induce a cephalic phase reflex as indicated by increased autonomic & endocrine responses in postmenopausal women.
详细描述
Moderate alcohol consumption has consistently been associated with lowered risk of developing type two diabetes mellitus compared to abstainers and heavy drinkers. However, the physiological mechanism for this is not known.
Two potential mechanisms will be investigated in this study to explain the findings from observational studies: One concerning more acute changes upon alcohol consumption (cephalic phase reflex) which could explain the observed improvement in postprandial glycemia after alcohol consumption; the other has to do with metabolic changes after more prolonged moderate alcohol consumption in gene expression of adipose tissue which might lead to improved insulin sensitivity. Both mechanisms will be discussed below.
Cephalic phase reflex Mere exposure to smell, sight, taste and textural attributes of foods elicits myriad digestive, endocrinologic, thermogenic, cardiovascular and renal responses. These responses are rapid (generally occurring in minutes of sensory stimulation), small (relative to the magnitude achieved when food is actually being metabolized) and transient (retuning to baseline levels within minutes). They are termed pre-absorptive or cephalic phase reflexes/responses (CPR) and refer to a set of food intake-associated autonomic and endocrine responses to the stimulation of sensory systems mainly located in the oropharyngeal cavity. Their function may be essential adaptive, preparing the digestive system for the reception, digestion and absorption of ingested nutrients.
The release of cephalic phase hormones occurs through activation of vagal efferent fibers in response to food-related sensory stimuli. Pancreatic polypeptide (PP) is a hormone almost exclusively under vagal control increases. Thus, the cephalic phase PP response is a sensitive indicator of vagal activation to food stimuli. PP levels rise up to 100% above baseline when individuals taste, chew and expectorate food while the magnitude of cephalic phase insulin release is relatively small (25% above baseline). The cephalic phase is by some considered as a reflex rather then a response as it is dependent on neural rather than nutrient-induced stimulation.
The physiological significance of the cephalic phase hormonal responses is demonstrated by experimental manipulations which inhibit or bypass cephalic phase insulin release. Under these circumstances, hyperglycemia and hyperinsulinemia are evident.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy as assessed by the health and lifestyle questionnaire (P8009 F02), physical examination and results of the pre-study laboratory tests
- •Caucasian postmenopausal females aged 65 years or younger at Day 01 of the study.
- •Body Mass Index (BMI) of 18 - 26 or 27 - 35 kg/m
- •Postmenopausal as assessed by self reported absence of menstrual periods for at least 12 months.
- •Alcohol consumption ≥ 5 and ≤ 22 standard units/week.
- •Normal Dutch eating habits as assessed by P8009 F
- •Voluntary participation.
- •Having given written informed consent.
- •Willing to comply with the study procedures, including refrain from drinking alcoholic drinks other then the wine provided by TNO during the entire study.
- •Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data for at least 15 years.
- •Willing to accept the disclosure of the financial benefit of participation in the study to the authorities concerned.
排除标准
- •Participation in any clinical trial including blood sampling and/or administration of substances up to 90 days before Day 01 of this study.
- •Participation in any non-invasive clinical trial up to 30 days before Day 01 of this study, including no blood sampling and/or oral, intravenous, inhalatory administration of substances.
- •Having a history of medical or surgical events that may significantly affect the study outcome, particularly metabolic or endocrine disease and gastrointestinal disorders.
- •Use of medication that may affect the outcome of the study parameters.
- •Having a family history of alcoholism.
- •Not having appropriate veins for blood sampling/cannula insertion according to TNO.
- •Reported unexplained weight loss or gain in the month prior to the pre-study screening.
- •Reported slimming or medically prescribed diet.
- •Reported vegan, vegetarian or macrobiotic.
- •Recent blood donation (<1 month prior to the start of the study).
- •Not willing to give up blood donation during the study.
- •Personnel of TNO Quality of Life, their partner and their first and second degree relatives.
- •Not having a general practitioner.
- •Not willing to accept information transfer concerning participation in the study, or information regarding her health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner.
- •Not willing your general practitioner to be notified upon participation in this study
结局指标
主要结局
Gene expression profiles in adipose tissue
时间窗: after four weeks of intervention
Pancreatic Polypeptide (PP)
时间窗: 0, 4, 8, 12, 16, 20 and 30 min after start of modified sham-feeding with either water, white wine or cake
次要结局
- Cytokines excreted from PBMCs after in vitro stimulation with LPS(after four weeks of intervention)