Modulation of Free Fatty Acids in Heart Failure Patients With Diabetes: Effect on Left Ventricular Function

Study Overview
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Brief Summary
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The investigators wish to investigate the the short term effect of low circulating free fatty acids in congestive heart failure patients with type 2 diabetes. Hypothesis: Low levels of circulating free fatty acids decrease myocardial and peripheral muscle lipid content, improves cardiac performance and exercise capacity.

Official Title
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Short Term Modulation of Circulating Free Fatty Acids in Heart Failure Patients With Type 2 Diabetes: Effect on Myocardial Lipid Content, Left Ventricular Function and Exercise Capacity

Conditions
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Heart Failure, Diabetes

Intervention / Treatment
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* Other: Metabolic substrate modulation
* Other: metabolic substrate modulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ejection fraction at or lower than 45% type 2 diabetes Exclusion Criteria: known s-creatinine >220mM known S-alanine aminotransferase >3 times normal upper limit other disabilitating conditions pregnancy insulin treatment

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High circulating free fatty acids<br>using Heparin af intralipid infusion for 8 hours | Other: Metabolic substrate modulation<br>* for high circulation free fatty acids: Heparin (250IE/hour) + intralipid (20%, 62 ml/hour).<br>|
| Active Comparator: Low circulation free fatty acids<br>using hyperinsulinaemic euglycemic clamp for 8 hours | Other: metabolic substrate modulation<br>* low circulating free acids: hyperinsulinaemic euglycemic clamp (0,8 mUkg/min) with venous blood glucose at 4,5-6,5 mM.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular function | Left ventricular systolic function (Ejection fraction, tissue velocity, Strain and strain rate). Left ventricular diastolic funtion (E/A ratio, E/e' ratio, IVRT) Cardiac output. All parameters measured at rest and peak exercise and outcome is difference between low and high ciculating free fatty acids. | 1-6 weeks | 
| intracellular lipid content | Magnetic Resonans proton spectroscopy (septal myocardial intracellular lipid content) Magnetic Resonans proton spectroscopy (Tibialis anterior muscle intracellular lipid content). Outcome is difference between low and high ciculating free fatty acids. | 1-6 weeks | 
| Exercise capacity and oxygen consumption | Using treadmill and continues oxygen consumption measurement. Outcome is difference between low and high ciculating free fatty acids. | 1-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional left ventricular function | regional speckle tracking during rest and peak exercise. Outcome is difference between low and high ciculating free fatty acids. | 1-6 weeks | 
| 6 minutes hall walk test | distance difference between low and high levels of circulating FFA. Outcome is difference between low and high ciculating free fatty acids. | 1-6 weeks | 
| metabolic and hormonal profile | bloodsamples | 1-6 weeks |