Vascular Function, Endothelin, and Inflammation in Pre-diabetic Obesity Versus Lean Healthy Controls
Overview
- Phase
- Phase 1
- Intervention
- Acute Salsalate
- Conditions
- Pre-diabetes
- Sponsor
- Indiana University
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Vascular Function
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
Aims:
- Does inflammation contribute importantly to concurrent defects in vascular and metabolic dysfunction in human pre-diabetic obesity?
- Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin?
- Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with lisinopril?
Detailed Description
We set out to pursue the following Aims: 1. Does inflammation contribute importantly to concurrent defects in vascular and metabolic dysfunction in human pre-diabetic obesity? Pilot studies were performed exploring the acute actions of salsalate on vascular function, the chronic actions of salasate in obese individuals, and actions of chronic salsalate to prevent vascular dysfunction induced by fatty acids in lean individuals. 2. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with metformin? No studies were performed 3. Are there benefits of anti-inflammatory treatment strategies in pre-diabetic obesity in the context of existing treatment with lisinopril? No studies were performed The intent of the current project is to efficiently and at low cost generate preliminary data along each of these lines of questioning, studying the minimum number of subjects required to assess the viability of the question using the current measurement approaches.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Arms & Interventions
Acute Salsalate
Nondiabetic lean and obese subjects will be studied in this arm. Subjects will be studied at baseline and after a single dose of oral salsalate.
Intervention: Acute Salsalate
Chronic Salsalate - Obese
Obese subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months' treatment with oral salsalate.
Intervention: Chronic salsalate
Chronic Salsalate - Lean
Lean subjects will be studied in this arm. Subjects will be studied at baseline and after 2 months' treatment with oral salsalate. The effects of an acute fatty acid infusion on vascular function will be measured on both occasions.
Intervention: Chronic salsalate
Outcomes
Primary Outcomes
Vascular Function
Time Frame: Measured at baseline and after a single oral dose of salsalate (Acute) or 2 months' treatment with salsalate (Chronic)
The primary endpoints of interest is flow-mediated vasodilation