ClinicalTrials.gov
ClinicalTrials.gov Menu

Production of Free Fatty Acids From Blood Triglycerides

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00911482
Recruitment Status : Completed
First Posted : June 2, 2009
Last Update Posted : November 7, 2012
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
Mayo Clinic

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The overall hypothesis of these studies is that circulating triglycerides, coming primarily from fat in the diet, are an important source of free fatty acids. Free fatty acids are the major fat fuel in the body, and when they are elevated in the blood they are thought to raise the risk of cardiovascular disease by causing insulin resistance (in some cases leading to diabetes), raising blood pressure, and other effects. The investigator will use sophisticated methods for tracing triglycerides and free fatty acids in the blood. These methods involve the administration of low doses of radioactive and stable isotopes of naturally occurring fats. The studies will determine the contribution of triglycerides to free fatty acids in normal people and also in people with diabetes.

Condition or disease
Diabetes Mellitus, Type 2 Insulin Resistance Dyslipidemias

Detailed Description:
Lipid energy is transported in the blood in several forms, including chylomicrons and free fatty acids (FFA). Chylomicrons are key elements in the absorption and storage of dietary fat, and also play a role in the pathogenesis of atherosclerosis via the production of remnant particles, but their role as a direct fuel source has not been explored. FFA are the major lipid fuel in the body, and increases in their concentration have been shown to cause insulin resistance, endothelial dysfunction and increases in the production of very low density lipoproteins. FFA are released into the blood through the action of hormone sensitive lipase on triglyceride stores in fat cells. Very little is known about the role of chylomicrons in FFA metabolism, but the potential contribution of chylomicrons to FFA is considerable, especially in people who consume high fat diets. Initial studies indicate that in addition to the role of chylomicrons in fat storage, a portion of chylomicron fatty acids are released as FFA in a process called "spillover". These studies indicate that the contribution of chylomicrons to FFA is increased in type 2 diabetes. A study of spillover in the splanchnic bed found very high rates of splanchnic spillover in overweight and obese individuals with hypertriglyceridemia. Extremely accurate and precise methods have been developed by the investigator for the measurement of the concentration and specific activity of FFA and chylomicron triglyceride fatty acids in plasma. In addition, a tracer method for accurately determining the kinetics of chylomicrons has been developed. In the proposed studies, the tracer technique will be used to systematically investigate the contribution of chylomicrons to total FFA availability. The technique will be applied to normal subjects at rest and after exercise, as well as subjects with type 2 diabetes mellitus and hypertriglyceridemia. Specifically, these studies will: 1) determine whether weight loss in people with type 2 diabetes reduces spillover from chylomicrons; 2) determine whether acute lowering of FFA with insulin infusion reduces spillover in nondiabetic individuals with dyslipidemia; 3) determine whether noninsulin-mediated lowering of FFA reduces spillover in diabetic individuals with dyslipidemia, and 4) determine whether obese, insulin-resistant individuals have increased spillover in the splanchnic bed.

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Observational
Actual Enrollment : 16 participants
Time Perspective: Cross-Sectional
Official Title: FFA Production From Triglyceride-Rich Lipoproteins
Study Start Date : June 2008
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012
Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
Diabetes/weight loss
12 individuals with type 2 diabetes and hypertriglyceridemia
Nondiabetic/hypertriglyceridemic
10 insulin resistant nondiabetic individuals with dyslipidemia
Normotensive/nondiabetic
10 insulin resistant, normotensive, nondiabetic individuals
Insulin resistant/dyslipidemic
14 insulin resistant nondiabetic individuals with dyslipidemia


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Spillover of free fatty acids from chylomicrons [ Time Frame: Measured at 1 to 6 days ]

Biospecimen Retention:   Samples Without DNA
Plasma samples obtained during the study are stored for lipid analysis.

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   35 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Volunteers from the region around Rochester, Minnesota who meet the inclusion criteria will be recruited.
Criteria

Inclusion Criteria:

  • Type 2 diabetes
  • Atherogenic dyslipidemia
  • Obesity

Exclusion Criteria:

  • Kidney disease
  • Liver disease
  • Coronary artery disease
  • Retinopathy
  • Neuropathy
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00911482


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: John M. Miles, MD Mayo Clinic
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: John M. Miles, MD, Mayo Foundation
ClinicalTrials.gov Identifier: NCT00911482     History of Changes
Other Study ID Numbers: 08-001493
R01HL067933 ( U.S. NIH Grant/Contract )
First Posted: June 2, 2009    Key Record Dates
Last Update Posted: November 7, 2012
Last Verified: November 2012

Keywords provided by Mayo Clinic:
Type 2 Diabetes
Dyslipidemia
FFA
Triglycerides
Tracers

Additional relevant MeSH terms:
Diabetes Mellitus
Insulin Resistance
Diabetes Mellitus, Type 2
Dyslipidemias
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Hyperinsulinism
Lipid Metabolism Disorders
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs