Lipid Biomarkers for Diabetic Heart Disease

Study Overview
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Brief Summary
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This study will test whether lowering the delivery of excess fats to the heart in persons with type-2 diabetes mellitus improves heart muscle function. The investigators will also test whether specific lipid molecular species in plasma can serve as biomarkers for diabetic heart disease.

Detailed Description
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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.

Official Title
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Lipid Biomarkers for Diabetic Heart Disease

Conditions
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Type II Diabetes Mellitus, Diabetes Complications

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: Placebo for fenofibrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenofibrate<br>One fenofibrate 160 mg capsule per day for 12 weeks | Drug: Fenofibrate<br> <br> * Other names: Lipofen;|
| Placebo Comparator: Placebo for fenofibrate<br>One inert sugar pill per day for 12 weeks | Drug: Placebo for fenofibrate<br> <br> * Other names: Sugar pill manufactured to mimic Fenofibrate 160 mg capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiac Diastolic Function as Measured by E' (cm/s) | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. | Baseline and 12 weeks | 
| Change in Cardiac Systolic Function as Measured by Fractional Shortening Percent | Change was measured by echocardiography and was calculated as the value at 12 weeks minus the value at baseline. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in C24:0/C16:0 Ceramide Ratio | Mass spectrometry-based quantification of the ratio of C24:0 ceramide to C16:0 ceramide in plasma. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Diabetic Cardiomyopathy, Triglycerides