Insulin Resistance in the Control of Intestinal Lipid Metabolism
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Meal triglyceride (TG) absorption
研究概览
简要总结
America's preferential consumption of high-fat/high-sugar foods is a driving force in the current epidemic of obesity and insulin resistance. Recent scientific observations suggest that the taste of food may play a role in how the body processes the food eaten in a meal. The intestine may play a central role in all aspects of dietary fat metabolism, from initial encounter with taste buds in the mouth to eventual triglyceride (TG) storage in the body.
The investigators hypothesize that elevated blood fats in insulin resistance are a result of elevated intestinal-TG secretion and poor communication of this organ to the rest of the body after meals.
In this study, meal feeding and sensory studies will be performed to determine whether the mechanism of taste-associated intestinal signaling leads to higher levels of blood fats after meals in 24 healthy, insulin resistant and type 2 diabetic subjects. Individuals will consume special meals the night before the tests and participate in sensory tests in the morning to analyze the effect of taste.
The goal of this work is to understand how insulin resistance may cause impaired signaling between the taste buds and the intestine to result in an elevation in blood lipids, which increases the risk for other chronic diseases. This study will generate data for a future study to understand how diabetes treatment affects this process.
详细描述
Subjects will participate in two screening visits to determine insulin resistance status and then participate in a single in-patient, clinical research center test.
There are no drugs used in this study. The goal is to test the physiological response to eating.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects (age 18-50y) will be categorized as:
- •lean/insulin sensitive (IS) (n=8, BMI </= 24 kg/m2 and SI ≥ 2.5 min-1 10-4 * per uU/mL)
- •overweight/obese IS (n=8, BMI 26-35 and SI >2.5 min-1 10-4 * per uU/mL)
- •overweight/obese insulin resistant (n=8, BMI 26-35 and SI <2.5 min-1 10-4 * per uU/mL).
- •Overweight/obese insulin resistant subjects will have a family history of diabetes as defined as at least one parent or grandparent with type 2 diabetes, or at least one other family member with type 2 diabetes.
- •Type 2 diabetic patients (BMI 26-35, and OGTT 2h glucose >/= 140 mg/dL.
排除标准
- •BMI over 35 kg/m2: We felt it prudent to limit the additional variability that could be caused by morbid obesity (and by diabetes), given the early stages of this research area.
- •Unusual eating habits (dietary fat< 30% or >40% of energy, skipping breakfast, day-long fasting, or allergies to milk). Habitual food intake can influence taste acuity and milk is used in the formulas to dissolve the isotopes.
- •Uncontrolled hypertension, or occasional or regular smoker, use of supplements or medications that interfere with lipid, protein, or carbohydrate metabolism or impact taste. For example, the hypertensive drugs thiazides or the supplement chondroitin sulfate or niacin, can be associated with impaired glucose tolerance. ACE inhibitors and beta-blockers and smoking can affect taste. Use of insulin in the case of type 2 diabetics.
- •Pregnancy (urine test), breastfeeding, or anemia (CBC with diff): Limitations of blood that can be drawn. Postmenopausal women frequently have increases in blood lipids since lack of estrogen influences lipid metabolism.
- •Alcohol intake: Males >140 g/week, females > 70 g/week. Excess EtOH increases lipid synthesis and secretion in the liver and whether it also has an impact on intestinal TG metabolism is unknown.
- •Fasting plasma TG >300 mg/dL. Extreme hypertriglyceridemia could be due to either elevations in VLDL or chylomicrons, either of which would impair our ability to resolve dietary metabolic processes.
- •Exclude those who need to consume acetaminophen-containing medications on a regular basis. Acetaminophen is administered with meals to assess gastric emptying.
- •Postmenopausal women.
结局指标
主要结局
Meal triglyceride (TG) absorption
时间窗: Change in plasma TG concentrations over 24 hr after meals and in response to an acute sensory stimulus
In vivo measurement of meal TG absorption is made using stable isotope administration into sequential meals (lunch and dinner) and analysis of plasma samples by GS/MS
次要结局
未报告次要终点
研究者
Elizabeth Parks
Professor
University of Missouri-Columbia