ADAM17 and Vascular Function in Diabetes

Targeting ADAM17 Activity for Correction of Vascular Insulin Resistance in Type 2 Diabetes

The objective of this project is to determine the extent to which administration of the dietary supplement phosphatidylserine (PS), a competitive inhibitor of ADAM17 sheddase activity, effects vascular function and insulin-stimulated leg blood flow in subjects with T2D.

As part of a randomized (1:1, experimental/placebo), double-blinded parallel design, each of the 34 subjects will complete 4 weeks (+/-4 days) of supplementation with either 900mg of a PS supplement or placebo. Assessment visits (2) will occur pre-intervention and post-intervention and include: 24-hour ambulatory blood pressure measurement (ABPM), Vitals, DEXA scan for body composition, fasting blood work, carotid-femoral pulse wave velocity (cfPWV), brachial and femoral artery FMDs, Femoral blood flow imaging during passive leg movement (PLM), glycocalyx integrity assessment via Glycocheck, and an oral glucose tolerance test (OGTT) with blood flow measurements and beat-to-beat sphygmomanometry via Finometer.

Inclusion Criteria:

1. Men and women with a BMI of 25-39 kg/m2, who are 45-64 years of age at randomization.
2. T2D patients classified based on physician diagnosis.
3. No vulnerable populations (e.g., prisoners, pregnant, children) will be enrolled.

Exclusion Criteria:

1. Cardiovascular disease including myocardial infraction, heart failure, coronary artery disease, stroke
2. History of chronic renal or hepatic disease
3. Active cancer
4. Autoimmune diseases
5. Immunosuppressant therapy
6. Hormone replacement therapy
7. Excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)
8. Current tobacco use
9. Pregnancy
10. Bodyweight change ≥5% within the last 6 months