Free Fatty Acids and Vascular Function in Subjects With Diabetes

Mass General Brigham

Status and phase

Completed

Phase 2

Phase 1

Conditions

Type 2 Diabetes Mellitus

Treatments

Drug: placebo

Drug: acipimox

Study type

Interventional

Funder types

Other

Identifiers

NCT00153179

2005P-000088

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

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