Precision Nutrition and Metabolic Function
Precision Nutrition and Metabolic Function
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.
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.
Inclusion Criteria:

 -  Metabolically normal 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 normal 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 abnormal 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%.

 Exclusion Criteria:

 -  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