Extracellular Vesicles, Insulin Action, and Exercise

Inclusion 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 ≥6 year.

• Has a body mass index of 20-24.99 or 25.0-45 kg/m2.

• Not diagnosed with Type 1 diabetes.

• Not currently engaged in >150 min/wk of exercise.

Exclusion Criteria:

• Participants with morbid obesity (BMI >45 kg/m2) and underweight patients (BMI: ≤18kg/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 screeningquestions (≥150 min of moderate/high intensity exercise)

• T2D with HbA1c ≥10.0%

• Participants who are smokers or who have quit smoking ≤2 years ago

• Participants prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IVinhibitors, Acarbose, SGLT-2 inhibitors within 6 year.

• Hypertriglyceridemic (≥400 mg/dl) and hypercholesterolemic (≥260 mg/dl) participantsas 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 comprehensivemetabolic panels).

• Hypertensive (≥160/100 mmHg) at time of screening.

• Abnormal liver function (reflective from comprehensive panel liver enzymes Alk (≥121IU/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 inthe investigator's opinion would interfere with or alter the outcome measures, orimpact 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).