Lipid Biomarkers for Diabetic Heart Disease

Screening procedures include 12-hour fasting blood draw, urine pregnancy testing for females,
completion of medical history questionnaire, and stress echocardiography to rule out coronary
artery disease or cardiomyopathy.

Subjects who meet screening criteria will return for visit 2, which consists of a urine
collection, 12-hour fasting blood draw, dual-energy X-ray absorptiometry (DXA) for body
composition, magnetic resonance spectroscopy analysis of the liver, and resting
echocardiogram for analysis of heart structure and function. Subjects will then be randomized
to treatment with fenofibrate (160 mg/d) or an identical-appearing placebo for 12 weeks. They
will be asked to continue their usual medications, diet and physical activity. Subjects will
receive a pedometer to wear daily to track their physical activity. Subjects will meet with
dietitians from the Lifestyle Intervention Core to complete a 24-hour dietary recall. They
will be instructed to record their daily blood glucose concentrations, distance walked and
any side effects, illnesses or stresses in a study-supplied log. Subjects will be instructed
to either email or fax the log to the study coordinator each week (or discuss by phone).

Subjects will return 6 weeks after starting intervention for visit 3 to ensure their medical
safety. Procedures at this visit include an interim medical history, urine pregnancy test for
females, blood draw to rule out untoward effects of the study drug on liver or kidney
function, pill count to assess compliance, review of logs of blood glucose, distance walked,
and side effects, illnesses or stresses, and meeting with a dietitian for a 24-hour dietary
recall.

Subjects will continue to take their study medication/placebo and keep logs of blood glucose
levels, distance walked, and side effects, illnesses and stresses for another 6 weeks. They
will return for visit 4 after 12 total weeks of intervention. Visit 4 involves a urine
collection, 12-hour fasting blood draw, review of subject logs, pill count, and 24-hour
dietary recall. In addition, magnetic resonance spectroscopy analysis of the liver and
resting echocardiogram analysis of the heart will be performed to determine if there have
been any changes in liver fat or heart function during the 12-week intervention.

Inclusion Criteria:

- Type 2 diabetes mellitus

Exclusion Criteria:

- body weight > 300 lb.

- HIV

- hypothyroid

- steroid medication, fenofibrate

- smoking

- BP > 140/90

- heart disease

- pregnant or lactating

- consumption of > 5 alcoholic drinks/wk

- creatinine > 1.5 mg/dL

- hematocrit < 28