Extracellular Vesicles, Insulin Action, and Exercise

Eligibility Criteria

• * Male or female 30 - 80 years old.
• * HbA1c \<5.7% and fasting glucose \<100mg/dl to be considered NGT
• * T2D diagnosis or confirmation HbA1c ≥6.5% and fasting glucose ≥126 mg/dl
• * Prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors ≥1 year.
• * Has a body mass index of 20-25 or 28-45 kg/m2.
• * Not diagnosed with Type 1 diabetes.
• * Not currently engaged in \>150 min/wk of exercise.
• * Participants with morbid obesity (BMI \>45 kg/m2) and under-/overweight patients (BMI: ≤18 or 25-27.99 kg/m2).
• * Intolerance to insulin
• * Evidence of type 1 diabetes and diabetics requiring insulin therapy.
• * Participants who have not been weight stable (≥2 kg weight change in past 6 months)
• * Participants who have been recently active in past 6 months via health screening questions (≥150 min of moderate/high intensity exercise)
• * T2D with HbA1c ≥8.0%
• * Participants who are smokers or who have quit smoking ≤5 years ago
• * Participants prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors within 1 year.
• * Hypertriglyceridemic (≥400 mg/dl) and hypercholesterolemic (≥260 mg/dl) participants as determined from LabCorp samples.
• * Kidney dysfunction as determined from LabCorp biochemical outcomes (e.g. creatinine (≥1.0 mg/dl), eGFR (≤59 ml/min/1.73), BUN (≥24 mg/dl) as derived from comprehensive metabolic panels).
• * Hypertensive (≥160/100 mmHg) at time of screening.
• * Abnormal liver function (reflective from comprehensive panel liver enzymes Alk (≥121 IU/L), AST (≥40 IU/L) and ALT (≥32 IU/L) via LabCorp).
• * History of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
• * Pregnant (as evidenced by positive pregnancy test) or nursing women
• * Participants with contraindications to participation in an exercise training program
• * Known hypersensitivity to perflutren (contained in Definity).
• * Anemic as confirmed by hematocrit (HCT) (women ≤36%, Men ≤38%) at time of screening.
• * Suggested infections at time of screening as confirmed by WBC (≥10.8 x10E3/uL) and/or platelets (≥450 x10E3/uL).