Precision Nutrition and Metabolic Function
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- Change in insulin sensitivity
研究概览
简要总结
The purposes of this study are: 1) to determine the mechanisms responsible for the development of cardiometabolic complications in some, but not all people with obesity; 2) determine the best dietary approach for cardiometabolic health; and 3) understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.
详细描述
Excess adiposity causes alterations in metabolic function including impaired glucose homeostasis and insulin resistance, which are important risk factors for type 2 diabetes (T2D) and cardiovascular disease (CVD). Not all people with obesity experience the typical metabolic complications associated with obesity. Approximately 25% of people with obesity are protected from the adverse metabolic effects of excess fat accumulation and are considered to be metabolically healthy based on their normal response to insulin. The mechanism(s) responsible for the differences in metabolic function among people with obesity is not known, but is likely to be multifactorial including dietary intake. The risk for developing T2D and CVD is also well known to increase with age, however, not all people that are metabolically healthy convert to a metabolically unhealthy phenotype over time. The mechanisms responsible for the stability of health status in some, but not all adults, are unclear. The overall goals of this study are to: i) determine the mechanisms responsible for the development of cardiometabolic complications in participants who will be carefully characterized into 3 distinct groups [metabolically normal lean, metabolically normal obese and metabolically abnormal obese], ii) to determine the optimal dietary approach for cardiometabolic health independent of weight change in people with metabolically abnormal obesity, and iii) perform a comprehensive longitudinal assessment of cardiometabolic health to understand why some people have a stable metabolic phenotype over time whereas cardiometabolic health improves or worsens in others.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Metabolically healthy lean subjects must have a body mass index (BMI) 18.5-24.9 kg/m², intrahepatic triglyceride (IHTG) content ≤5%, serum triglyceride (TG) concentration <150 mg/dl, fasting plasma glucose concentration <100 mg/dl, 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
- •Metabolically healthy obese subjects must have a BMI 30-49.9 kg/m²; IHTG content ≤5%, serum TG concentration <150 mg/dl, fasting plasma glucose concentration <100 mg/dl, 2-hr OGTT plasma glucose concentration ≤140 mg/dl, and HbA1C ≤5.6%.
- •Metabolically unhealthy obese subjects must have a BMI 30-49.9 kg/m²; IHTG content ≥5.6% and fasting plasma glucose concentration ≥100 mg/dl or 2-hr OGTT plasma glucose concentration ≥140 mg/dl or HbA1C ≥5.7%.
排除标准
- •medical, surgical, or biological menopause;
- •previous bariatric surgery where the gastrointestinal tract is reconstructed such as Roux-en-Y, sleeve gastrectomy and biliopancreatic diversion surgeries;
- •laparoscopic adjustable gastric band (lab band) surgery within the last 3 years;
- •structured exercise ≥250 min per week (e.g., brisk walking);
- •unstable weight (>4% change during the last 2 months before entering the study);
- •significant organ system dysfunction (e.g., diabetes requiring medications, severe pulmonary, kidney or cardiovascular disease);
- •cancer or cancer that has been in remission for <5 years;
- •polycystic ovary syndrome;
- •major psychiatric illness;
- •conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders);
- •severe anemia;
- •regular use of tobacco products;
- •excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women);
- •use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study;
- •use of antibiotics in last 60 days;
- •pregnant or lactating women;
- •vegans, vegetarians, those with lactose intolerance and/or severe aversions/sensitivities to eggs, fish, nuts, wheat and soy, and/or any individuals with food allergies that induce an anaphylactic response;
- •persons who are not able to grant voluntary informed consent
研究组 & 干预措施
Metabolically unhealthy obese - Mediterranean diet
Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the Mediterranean diet group.
干预措施: Annual follow-up testing for 5 years (Other)
Metabolically healthy obese - Mediterranean diet
Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the Mediterranean diet group.
干预措施: Mediterranean diet (Behavioral)
Metabolically healthy obese - Mediterranean diet
Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the Mediterranean diet group.
干预措施: Annual follow-up testing for 5 years (Other)
Metabolically healthy obese - Low-carbohydrate ketogenic diet
Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-carbohydrate ketogenic diet group.
干预措施: Low-carbohydrate, ketogenic diet (Behavioral)
Metabolically healthy obese - Low-carbohydrate ketogenic diet
Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-carbohydrate ketogenic diet group.
干预措施: Annual follow-up testing for 5 years (Other)
Metabolically normal obese - Low-fat diet
Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-fat diet group.
干预措施: Low-fat diet (Behavioral)
Metabolically normal obese - Low-fat diet
Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-fat diet group.
干预措施: Annual follow-up testing for 5 years (Other)
Metabolically unhealthy obese - Mediterranean diet
Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the Mediterranean diet group.
干预措施: Mediterranean diet (Behavioral)
Metabolically unhealthy obese - Low-carbohydrate ketogenic diet
Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-carbohydrate, ketogenic diet group.
干预措施: Low-carbohydrate, ketogenic diet (Behavioral)
Metabolically unhealthy obese - Low-carbohydrate ketogenic diet
Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-carbohydrate, ketogenic diet group.
干预措施: Annual follow-up testing for 5 years (Other)
Metabolically unhealthy obese - Low-fat diet
Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-fat diet group.
干预措施: Low-fat diet (Behavioral)
Metabolically unhealthy obese - Low-fat diet
Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-fat diet group.
干预措施: Annual follow-up testing for 5 years (Other)
Metabolically healthy lean
Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content.
干预措施: Annual follow-up testing for 5 years (Other)
结局指标
主要结局
Change in insulin sensitivity
时间窗: Performed annually for 5 years
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Insulin sensitivity
时间窗: Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
次要结局
- Change in 24-hour hormone concentrations(Performed annually for 5 years)
- Change in fat mass and fat free mass(Performed annually for 5 years)
- Exosome-mediated intercellular signaling(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in exosome-mediated intercellular signaling(Performed annually for 5 years)
- Intrahepatic triglyceride content(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in intra-hepatic triglyceride content(Performed annually for 5 years)
- Abdominal adipose tissue volumes(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in carotid artery intima media thickness(Performed annually for 5 years)
- Change in transcriptome in blood, muscle and adipose tissue(Performed annually for 5 years)
- Change in abdominal adipose tissue volumes(Performed annually for 5 years)
- Cardiac structure and function(Baseline only (cross-sectional comparison of metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in endothelial function(Performed annually for 5 years)
- Transcriptome in blood, muscle and adipose tissue(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Carotid artery intima media thickness(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in 24-hour glucose concentrations(Performed annually for 5 years)
- 24-hour hormone concentrations(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in Insulin clearance(Performed annually for 5 years)
- Fat mass and fat free mass(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in gut microbiome(Performed annually for 5 years)
- Arterial stiffness(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in arterial stiffness(Performed annually for 5 years)
- 24-hour glucose concentrations(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- β-cell function(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Insulin clearance(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Leg adipose tissue volumes(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in leg adipose tissue volumes(Performed annually for 5 years)
- Gut microbiome(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)
- Change in β-cell function(Performed annually for 5 years)
- Change in cardiac structure and function(Performed annually for 5 years in metabolically healthy obese and metabolically unhealthy obese subjects.)
- Endothelial function(Baseline only (cross-sectional comparison of metabolically healthy lean, metabolically healthy obese and metabolically unhealthy obese subjects).)