Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- peak decrease in overnight respiratory exchange ratio
研究概览
简要总结
This study is designed to test the reliability of a novel procedure for measuring metabolic flexibility, i.e., the ability to quickly adapt macronutrient oxidation to macronutrient availability, in a respiratory chamber. The investigators will compare paired measurements of metabolic flexibility determined 5-7 days apart in a metabolic chamber to assess reliability. The investigators will also compare their novel method of measuring metabolic flexibility in a respiratory chamber with a more convention method, metabolic flexibility during a hyperinsulinemic clamp.
详细描述
Metabolic flexibility (METFLEX) is the ability to adapt fuel oxidation to fuel availability and energy demands. Impaired METFLEX is associated with weight gain, ectopic lipid deposition, insulin resistance, and the potential development of type 2 diabetes. Even if impaired METFLEX shows promise as an early predictor of future metabolic dysfunction, longitudinal studies have been lacking because of the absence of simple methods for assessing METFLEX. This project will further validate (reproducibility and comparison with hyperinsulinemic-euglycemic clamps) a novel approach for measuring METFLEX recently developed by the PI.
METFLEX is commonly measured during a hyperinsulinemic-euglycemic clamp. Yet, this technique is questioned because it relies on a non-physiological stimulus (intravenous glucose and insulin) and inherently suppresses fat oxidation via non physiological hyperinsulinemic conditions. In contrast, impaired fat oxidation in response to a high-fat meal is a more physiological indicator of metabolic inflexibility. The investigators have recently developed a method for measuring METFLEX by assessing the dynamics in respiratory exchange ratio (RER) in response to a high-fat standardized dinner in a whole-body room indirect calorimeter. Securing extramural funding for the aforementioned longitudinal studies employing this novel methodology is presently limited due to a lack of the following preliminary data: 1) quantification of the intra-subject variability of this novel METFLEX measure to perform power calculations (sample size) in large-scale prospective clinical trials, and 2) comparison of our method to a more accepted measurement of METFLEX. The overarching goal of this method development project is to generate reproducibility and validity data of The investigators' new assessment of METFLEX in a whole-body room indirect calorimeter against the METFLEX measured by a hyperinsulinemic-euglycemic clamp.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between 18.5 kg/m^2 and 35 kg/m^2 (±0.5 kg/m^2 will be accepted)
- •Willing to consume pre-prepared meals
- •Non pregnant
- •Bilateral oophorectomy or use of the following contraceptive methods (females only):
- •monophasic oral contraceptives
- •progesterone-only oral contraceptives
- •injectable or implantable progesterone-only contraceptives
排除标准
- •Unstable weight in the last 3 months [gain or loss >7 lb (or 3.2 kg)]
- •Currently working shift work
- •Smoking or use of tobacco products within the last 3 months
- •History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL
- •Average screening blood pressure >140/90 mmHg
- •Previous bariatric surgery (or other surgeries) for obesity or weight loss
- •Use of medications affecting metabolism or sleep**
- •History of cardiovascular disease, neurological disease, or other chronic diseases that affect sleep or metabolism
- •Pregnant, planning to become pregnant, or breastfeeding
- •Adherence to special restrained diets (e.g., low-carbohydrate, low-fat, or vegetarian/vegan diets) over the last 3 months.
- •Sporadic use of these medications is acceptable (however, enrollment will be evaluated on a case-by-case basis). If taking sporadically, participants should not be taking the medication for 1-month prior to the first visit.
- •NOTE: Participants may also be excluded if deemed medically necessary by study Medical Investigator.
结局指标
主要结局
peak decrease in overnight respiratory exchange ratio
时间窗: 12 hours
mean of peak decrease in respiratory exchange ratio (baseline values -nadir values) following the test meal during an overnight stay in a respiratory chamber. Peak values are defined as the lowest respiratory exchange ratio value measured during the sleep period, 11pm-5am Baseline values are measured 1h prior to meal (5:00-5:45pm) An increase in this value indicates increased metabolic flexibility.
change in respiratory exchange ratio during high-dose insulin infusion
时间窗: 4.5 hours
mean of peak increase in respiratory exchange ratio during a 80 mU/m\^2/min insulin infusion (insulin stimulated - baseline values) that is conducted during an hyperinsulinemic-euglycemic clamp procedure.. Insulin-stimulated values are defined as the mean respiratory exchange ratio value measured during the final 30 min of a 2 hour 80 mU/m\^2/min insulin infusion. Baseline values are measured 30 min prior to the start of the hyperinsulinemic-euglycemic clamp procedure. An increase in this value indicates increased metabolic flexibility.
次要结局
- respiratory exchange ratio/food quotient (RER:FQ ratio)(12 hours)
- slope of respiratory exchange ratio(12 hours)
- change in respiratory exchange ratio during low-dose insulin infusion(4.5 hours)
- Time to nadir respiratory exchange ratio(12 hours)
- Time to food quotient(12 hours)
研究者
David McDougal
Assistant Professor - Research
Pennington Biomedical Research Center