Clinical trial NCT00153179: Free Fatty Acids and Vascular Function in Subjects With Diabetes
Official title: The Impact of Free Fatty Acid Reduction on Vascular Function and Skeletal Muscle Glucose Utilization in Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: insulin resistance
insulin signaling
endothelium-dependent vasodilation
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2005-09-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility 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 alternative 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

Primary outcomes:
measure: Flow-mediated Dilation After Placebo or Acipimox Treatment Between Healthy Controls and Those With Metabolic Syndrome
timeFrame: 7 days
measure: Difference in Insulin-mediated Skeletal Muscle Glucose Utilization Between Test Agent and Placebo
timeFrame: baseline, 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Mark Creager, M.D.
role: PRINCIPAL_INVESTIGATOR
References: