Clinical Trials

Inclusion Criteria:

• Age, 18-65 years old.
• Ability to sign informed consent form.
• Body mass index (BMI), 22-25 kg/m^2 (lean subjects), 30-45 kg/m^2 (subjects with obesity).
• Lean subjects are characterized by a BMI of 18 to 25 kg/m^2. However in our experience (Dr. De Filippis’ unpublished data), subjects with BMI < 22 kg/m^2 have small amounts of subcutaneous fat at the abdominal area and collection of 3-5g of adipose tissue becomes challenging.  Clinically, obesity is defined as BMI > 30 kg/m^2. However, research data from our laboratories over the years show more homogenous responses in metabolic responses in subjects with obesity that have higher BMI values. Therefore, studying subjects with BMI > 35 kg/m^2 (i.e., differ considerably in the degree of obesity), enhances our study design, and given also the inconsistent effects of obesity on metabolism resulting from classifying obesity based on BMI alone. We will not study humans with BMI > 45 kg/m2 to minimize variance in the measured responses in the obese subjects group, as well as for practical considerations related to obtaining muscle biopsies from subjects with extreme obesity (we have previously successfully obtained tissue biopsies from subjects with obesity at the BMI range proposed herein).
• Matsuda insulin sensitivity index (ISI), lean > 7, subjects with obesity < 4 (i.e., the greater the ISI value the more insulin sensitive the individual). Although, overall, we expect subjects with obesity to be less insulin sensitive, this response can vary greatly within subjects with obesity. Therefore, we will be able to clearly distinguish in our studies responses between subjects with obesity and insulin resistance and lean, insulin sensitive subjects. Together, the cut off criteria for both BMI and insulin sensitivity provide a robust study design with respect to the aims of our proposed studies, and in a way that will increase the reproducibility of our findings in larger cohorts.

Exclusion Criteria:

• Evidence of diabetes (subjects will be excluded based on hyperglycemia-defined criteria and according to the American Diabetes Association criteria for the diagnosis of diabetes that include fasting plasma glucose > 125 mg/dl, 2-h plasma glucose ≥ 200 mg/dl during OGTT, or A1C ≥ 6.5%; however, subjects with A1C 5.7–6.4%, impaired fasting glucose, or impaired glucose tolerance, indicative of insulin resistance, will be included, because the focus of the proposed studies is on humans with obesity/insulin resistance.
• Use of anti-hyperglycemic medications, anticoagulants including Coumadin, or any antiaggregants. NSAIDs will be asked to be discontinued about 7 days before biopsies procedures.
• Supplements affecting inflammation, lipid or glucose (turmeric, vitamin D, cinnamon, fish oil, red rice yeast, krill oil).
• Presence of acute illness.
• History of liver disease.
• Uncontrolled metabolic disease, including renal disease.
• Heart disease.
• Anemia (Hb 13.5 g/dL in males; 12.0 g/dL in females, or Hct < 38.3% in males; < 35.5% in females).
• Use of anabolic steroids or corticosteroids (within 3 months).
• Not classified as physically inactive/sedentary based on the Stanford Brief Activity Survey (SBAS); physical activity alters metabolic activities and for that reason we will focus our studies only in physically inactive individuals as determined using the SBAS tool.
• Current participation in a weight-loss regimen. Being in a weight-loss regimen alters the metabolic responses, in a way that is not reflective of a frank obese state.
• Recent weight gain or loss (> 10% of total body weight in last 6 months).
• Extreme dietary practices (i.e., vegan, vegetarian).
• Smoking.
• Pregnancy.
• Gastro-intestinal surgery/gastric bypass surgery.
• Any other condition or event considered exclusionary by the study team/physician..