Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls
Condition: Pre-diabetes; Obesity
MeSH terms: Obesity; Prediabetic State; Glucose Intolerance; Inflammation
Intervention: Chronic salsalate; Acute Salsalate
Intervention description: Subjects will receive 2 months of treatment with 4 gram/day of oral salsalate divided into 3 doses.; Subjects will receive a single oral dose of 2 gram of oral salsalate
Intervention MeSH terms: Salicylsalicylic acid; Sodium Salicylate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Vascular function; Glucose tolerance; Obesity; Pre-diabetes

Summary:

      Aims:

        1. Does inflammation contribute importantly to concurrent defects in vascular and metabolic
           dysfunction in human pre-diabetic obesity?

        2. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in
           the context of existing treatment with metformin?

        3. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in
           the context of existing treatment with lisinopril?
    

Eligibility criteria:

        Inclusion Criteria:

          -  healthy

          -  normotensive (BP<140/95 mmHg)

          -  lean and obese

          -  18 and 55 years

          -  women must be premenopausal

        Exclusion Criteria:

          -  use of pharmacologic agents or recreational drugs, with the exception of occasional
             use of non-narcotic pain medications

          -  blood pressure (>140/90 mmHg)

          -  elevated cholesterol (LDL >130 mg/dL)

          -  diabetes mellitus (by ADA criteria)

          -  evidence of coronary and/or peripheral vascular disease by history and physical exam

          -  >5 kg change in weight in the preceding 3 months

          -  chronic systemic illness with recognized metabolic effects

          -  hepatitis C and HIV

          -  recognized systemic inflammatory or autoimmune processes such as rheumatoid arthritis
             or systemic lupus erythematosis

          -  Raynaud's phenomenon or other abnormalities of hand or finger perfusion

          -  regular participation in endurance or high-performance athletic activity

          -  history of aspirin or salsalate sensitivity including aspirin-induced asthma

          -  prior treatment with salsalate, pentoxyfilline, or monoclonal anti-TNFalpha antibodies

          -  pregnancy

          -  liver transaminase levels >3 times the upper limit of normal

          -  creatinine >1.5 mg/dL

          -  history of a cellular immunodeficiency-related opportunistic infections, such as an
             endemic mycosis (eg. histoplasmosis) or mycobacterial infection (eg tuberculosis)

          -  reactive tuberculin skin test

          -  history of malignancy except for basal cell carcinoma of the skin