Overview
This study aims to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp).
Description
Drop-outs will be replaced; data will be used as much as can be. Subjects will undergo a Screening visit to assess eligibility and will then be scheduled to undergo 2 outpatient US treatment visits.
On day three subjects first undergo a third ultrasound session and then will either undergo Oral Glucose Tolerance Test (OGTT) with carbon13 (13C-glucose) tracer administration and subsequent NMR spectroscopy OR if enrolled into the HEC study arm will undergo euglycemic clamp testing. Following these procedures there will be an approximately two-week follow-up observational Period (with CGM). A two-week washout period will be followed by another cycle of the same procedures of either OGTT/NMR or HEC study, respectively.
Eligibility
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.
- A past medical history of abnormal glucose control and carry a diagnosis of T2D
according to current ADA criteria:
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.