Free Fatty Acids and Vascular Function in Subjects With Diabetes
| Status: | Completed |
|---|---|
| Conditions: | Diabetes, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 9/27/2018 |
| Start Date: | September 2005 |
| End Date: | March 2013 |
The Impact of Free Fatty Acid Reduction on Vascular Function and Skeletal Muscle Glucose Utilization in Type 2 Diabetes Mellitus
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.
adipocytes will restore insulin-mediated endothelium-dependent vasodilation and skeletal
muscle glucose metabolism in subject with type 2 diabetes.
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.
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.
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
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