Effects of Eicosapentaenoic Acid on Endothelial Function in Diabetic Subjects

Thirty adults aged 30-75 y will be randomized to either 4 g/d of eicosapentaenoic acid or no
drug for 12 weeks. Endothelial function will be measured at baseline and after 12 weeks. in a
secondary aims, we will evaluate effects of eicosapentaenoic acid (EPA) on plasma levels of
c-reactive protein, oxidized low-density lipoprotein cholesterol, and endothelin-1.

Inclusion Criteria:

- Age 30+ years

- Hypertriglyceridemia (150-400 mg/dl)

- Statin use for at least six months at the time of screening

- Type 2 diabetes treated with diet and/or oral hypoglycemic agents diagnosed 1+ year

- Ability to provide informed consent and provide blood samples

- Willingness to abstain from fish oil, EPA, over the counter niacin, and other omega-3
fatty acid supplements during the study period (12 weeks)

- Ability to travel to the study site at Brigham and Women's Hospital for 3 study visits

- Reactive hyperemia index (RHI) of ≤ 2.0

Exclusion Criteria:

- Eating disorder or heavy drinkers

- Treatment with chronic prescription pharmacotherapy for metabolic or cardiovascular
disease management or risk factor modification

- Pregnant or lactating women

- Statin use <6 months at the time of screening

- Allergy to EPA, fish oil, or other omega-3 fatty acids

- Current use of insulin, cyclophosphamide, estrogen, fibrates, niacin, hormone
replacement therapy, testosterone, oral contraceptives, growth hormones, insulin-like
growth factor-1, and other systemic steroids.

- Inability to provide informed consent or blood samples

- History or prevalent diagnosis of cancer, asthma, kidney insufficiency, stroke,
seizures, allergic disorders, or congestive heart failure

- Diagnosis of diabetes < 1 year prior to enrollment

- Intention to move out of greater Boston area within one year

- Current use of omega-3 supplements, fish oil, or >2 servings of fish per week

- Bleeding disorder or uncontrolled endocrine (i.e., thyroid) or metabolic disorders

- Treatment with blood thinning drugs (i.e. warfarin and clopidogrel)

- Major surgical operation 3 months before or after screening

- Organ transplantation

- Current participation in another trial or plan to do so during the study

- Inability to give informed consent or to travel to the study center at Brigham and
Women's Hospital

- RHI of >2.0

- Triglycerides <150 mg/dl or >400 mg/dl

- Body mass index of 40+ kg/m2