This study will test the hypothesis that reduction in release of free fatyy acids from adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal muscle glucose metabolism in subject with type 2 diabetes.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: acipimox	Phase I Phase II

Further Study Details: 

Primary Outcomes: difference in endothelium-dependent vasodilation between test agent and placebo; difference in flow-mediated, endothelium-dependent brachial artery vasodilation between test agent and placebo; difference in insulin-mediated skeletal muscle glucose utilization between test agent and placebo
Expected Total Enrollment:  100

During the past two decades, there has been a steady increase in the incidence of diabetes mellitus, such that nearly 17 million people are now afflicted. The vast majority of these have type 2 diabetes. Over the next 40 years, the type 2 diabetic population in the United States is expected to increase to nearly 30 million.

Diabetes substantially increases the risk of atherosclerosis, and thereby, cardiovascular morbidity and mortality. Indeed, cardiovascular disease causes more than 50% of the mortality in patients with diabetes. People with type 2 diabetes manifest two cardinal signs of dysmetabolism: hyperglycemia and insulin resistance. Insulin resistance is a progressive phenomenon that occurs well before the onset of frank diabetes, and results in alterations in insulin signaling. Experimental studies suggest that insulin signaling is required for vascular homeostasis, and its impairment is associated with endothelial dysfunction. In the clinical setting, insulin resistance is associated with atherosclerosis and predicts cardiovascular events independent of hyperglycemia. Therefore, we will study the importance of insulin signaling in endothelial biology in humans and the effects of free fatty acids on endothelial function in people with type 2 diabetes.

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• type 2 diabetes mellitus (as defined by the National Diabetes Data Group)
• normal cardiovascular exam
• non smoker (for 1 year prior to entry)
• Healthy volunteers
• no known medical problems
• normal cardiovascular exam
• fasting glucose < 110 mg/dL
• non-smoker (for 1 year prior to entry)

Exclusion Criteria:

Type 2 Diabetics

• untreated hypertension (>140/90 mmHg)
• untreated hypercholesterolemia (LDL > 75th percentile for age)
• cigarette smoking within 1 year
• neuropathy requiring medication
• nephropathy (> 300mg/24 hour urinary albumin, or serum creatinine > 1.4 mg/dL
• abnormal cardiovascular exam
• treatment with thiazolidinedione within 1 year
• post-menopausal women taking hormone replacement therapy

(Note: subjects taking angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) must stop these medications for 2 weeks prior to taking study drug. If blood pressure rises to >140/90, subjects will be prescribed an alternitive medication or be withdrawn from the study.

Healthy Volunteers

• abnormal cardiovascular exam
• use of prescription medications
• fasting glucose > 110mg/dL
• cigarette smoking within 1 year

Please refer to this study by ClinicalTrials.gov identifier  NCT00153179

Alison Goldin, BA      617 732-6320    agoldin@partners.org
Adnan Prsic, BA      617 732-6320    aprsic@partners.org

Massachusetts
      Brigham & Women''''s Hospital, Boston,  Massachusetts,  02115,  United States; Recruiting

Study chairs or principal investigators

Mark Creager, M.D.,  Principal Investigator,  Brigham and Women''''s Hospital   

Study ID Numbers:  2005P-000088
Last Updated:  September 12, 2005
Record first received:  September 8, 2005
ClinicalTrials.gov Identifier:  NCT00153179
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-09-13