Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects

Inclusion criteria

• Age 40-65 years inclusive
• Men and women
• Able to provide written, informed consent
• Weight stable (± 3 kg) during the 3 months prior to enrollment
• BMI ≥ 30 kg/m2; body weight ≤ 106 kg
• Resting blood pressure ≥ 110/60 mmHg and ≤ 150/100 mmHg

Exclusion criteria

• Known coronary artery disease, angina or heart failure
• Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose >125mg/dL)
• Bleeding disorders
• Hemoglobin level < 12.5 g/dL for women; < 13.0 g/dL for men
• Acute or chronic infections
• Hepatitis and/or cirrhosis (AST or Alanine Aminotransferase 2.5 times upper limit of normal)
• Severe asthma or chronic obstructive pulmonary disease
• Renal insufficiency (creatinine > 1.6 mg/dL)
• Prior bariatric surgery
• Inflammatory bowel disease or malabsorption
• Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
• Psychiatric or eating disorders
• Untreated or inadequately controlled thyroid (abnormal TSH) or other endocrine disorders
• Active rheumatoid arthritis or other inflammatory rheumatic disorder
• Pregnant or nursing women
• Presence of clinically significant abnormalities on electrocardiogram
• Smoking (within the last 3 months)
• Known hypersensitivity to nesiritide or any of its excipients
• Poor intravenous access
• Use of medications: a) nitrates, b) beta-blockers, c) digoxin, d) anti-diabetic agents, e) oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable), f) chronic use of aspirin or other non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors, g) other drugs known to affect immune or metabolic function and h) orlistat, phenteramine or other weight loss or anorectic agents.