Mechanisms of Ultrasound Neuromodulation Effects in Diabetes

Inclusion Criteria: Type 2 diabetic (T2D) subjects must be aged 18-80 and must be able to provide written informed consent All subjects must have had T2D for at least 3 months prior to study enrollment. All subjects must be either on diet and exercise or oral antidiabetic agents alone, not on insulin or any form of insulin or GLP-1 receptor agonists. Subjects must demonstrate: A past medical history of abnormal glucose control and carry a diagnosis of T2D according to current ADA criteria: A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis or A hemoglobin A1c (HbA1c) level of 6.5% or higher. Be willing to carry a continuous glucose monitor for at least 10 days. Be willing to follow all required instructions by study personnel and appear for the required laboratory assessments, including euglycemic clamps and OGTT. Exclusion Criteria: BMI >40kg/m2. Untreated proliferative retinopathy Creatinine clearance < 60 ml/min/1.73 m2. Serum creatinine ≥1.5 mg/dL Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures Active infection including hepatitis C, hepatitis B, HIV, Any history of Active alcohol abuse History of non-adherence to prescribed regimens Baseline Hgb < 10.5 g/dL in females, or < 13 g/dL in males History of coagulopathy or medical condition requiring long-term anticoagulant therapy (low-dose aspirin treatment is allowed) Co-existing cardiac disease with active medication titration. Patients on stable meds without active cardiac complications permitted. Liver function tests outside of 3xUL of normal range GI disorders potentially interfering with the ability to absorb oral medications and h/o upper GI surgery that might have changed anatomy in the target areas. Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes.