FFA Hypertension and Inflammation in Lean and Obese Subjects (FFAADA)

• ClinicalTrials.gov Identifier: NCT00721617
• Recruitment Status: Completed
• First Posted: July 24, 2008
• Results First Posted: July 27, 2015
• Last Update Posted: July 27, 2015
• Sponsor: Emory University
• Collaborator: American Diabetes Association
• Information provided by (Responsible Party): Guillermo Umpierrez, Emory University

Study Description

Brief Summary:

Although a large number of obese patients develop high blood pressure, the cause is unknown. The purpose of this study is to look at the effect of high fatty acids (a type of fat) in the development of high blood pressure in obese people.

Condition or disease	Intervention/treatment	Phase
Diabetes; Hypertension; Obesity	Other: Intralipid 20%; Other: Normal Saline; Other: Oral fat load	Not Applicable

Detailed Description:

Recent studies indicate that increased levels of a circulating fat (free fatty acids or FFAs) increases blood pressure, impairs endothelial (vascular) function, and increases inflammatory markers in subjects with and without diabetes. The effects of FFA on blood pressure and vasculature have not been fully investigated. A group of 12 obese nondiabetic, normotensive subjects will be admitted to the Grady Clinical Research Center (GCRC) on separate 4 occasions. Research subjects will receive, in random order, a 8-hour intravenous (IV) infusion of Intralipid 20% at 40 mL/h (a fat solution), 8-hour IV infusion of normal saline at 40 mL/h, 8-hour IV infusion of dextrose (sugar) 10% at 40 mL/h, and a 8-hour intravenous (IV) infusion combination of Intralipid 20% and dextrose 10% at 40mL/h.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Free Fatty Acids-Induced Hypertension, Endothelial Dysfunction, Inflammation, Insulin Resistance, and Autonomic Dysfunction in Lean and Obese Subjects
• Study Start Date: April 2009
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: June 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Obese subjects; Obese normotensive subjects will receive 24 hour challenges on 3 separate occasions, in a random order, with IV Normal Saline at 20ml/hour, IV Intralipid (20% solution at 20 ml/hour and an oral fat load (96g/24 hours)	Other: Intralipid 20%; Lean and obese normotensive subjects will receive Intralipid 20% infusion. Intralipid is an oil-in-water emulsion derived from egg phospholipids, soybean, and glycerol. The Intralipid 20% long-chain triglyceride emulsion contains: 200 g of soy bean oil; 12 g of egg yolk; 25 g of glycerol. The emulsion is composed of the following free fatty acids (FFAs): linoleic acid: 50%, oleic acid: 26%, palmitic acid: 10%, stearic acid: 9%, egg yolk, phospholipids: 3.5% It will be given intravenously at 20 ml/hr (96 g/24 h) for 24 hours.; Other: Normal Saline; Lean and obese normotensive subjects will receive normal saline at 20 ml/hr for 24 hours.; Other: Oral fat load; Lean and obese normotensive subjects will receive an oral fat load at 96 g/24hr. The oral liquid fat load will be given in equal amounts (16 g) every 4 hours (total 96 g over 24 hours).
Active Comparator: Lean subjects; Lean normotensive subjects will receive 24 hour challenges on 3 separate occasions, in a random order, with IV Normal Saline at 20ml/hour, IV Intralipid (20% solution at 20 ml/hour and an oral fat load (96g/24 hours)	Other: Intralipid 20%; Lean and obese normotensive subjects will receive Intralipid 20% infusion. Intralipid is an oil-in-water emulsion derived from egg phospholipids, soybean, and glycerol. The Intralipid 20% long-chain triglyceride emulsion contains: 200 g of soy bean oil; 12 g of egg yolk; 25 g of glycerol. The emulsion is composed of the following free fatty acids (FFAs): linoleic acid: 50%, oleic acid: 26%, palmitic acid: 10%, stearic acid: 9%, egg yolk, phospholipids: 3.5% It will be given intravenously at 20 ml/hr (96 g/24 h) for 24 hours.; Other: Normal Saline; Lean and obese normotensive subjects will receive normal saline at 20 ml/hr for 24 hours.; Other: Oral fat load; Lean and obese normotensive subjects will receive an oral fat load at 96 g/24hr. The oral liquid fat load will be given in equal amounts (16 g) every 4 hours (total 96 g over 24 hours).

Outcome Measures

Primary Outcome Measures :

1. Change in Flow-mediated Dilation From Baseline to 4 Hours [ Time Frame: Baseline, 4 hours ]
   Endothelium-dependent brachial artery flow-mediated dilation (FMD) was assessed. Ultrasound images of the brachial artery were obtained and arterial diameters were measured with customized software. FMD is expressed as the change in diameter from baseline to 4 hours.
2. Change in Systolic Blood Pressure From Baseline to 4 Hours [ Time Frame: Baseline, 4 hours ]
   Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 4 hour systolic blood pressure from baseline systolic blood pressure.
3. Change in Systolic Blood Pressure From Baseline to 8 Hours [ Time Frame: Baseline, 8 hours ]
   Systolic blood pressure is the amount of pressure your heart generates when pumping blood through your arteries to the rest of your body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 8 hour systolic blood pressure from baseline systolic blood pressure.
4. Change in Diastolic Blood Pressure From Baseline to 4 Hours [ Time Frame: Baseline, 4 hours ]
   Diastolic blood pressure is the amount of pressure in your arteries when your heart is at rest between beats. Current guidelines identify normal diastolic blood pressure as lower than 80 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 4 hour diastolic blood pressure from baseline diastolic blood pressure.
5. Change in Diastolic Blood Pressure From Baseline to 8 Hours [ Time Frame: Baseline, 8 hours ]
   Diastolic blood pressure is the amount of pressure in your arteries when your heart is at rest between beats. Current guidelines identify normal diastolic blood pressure as lower than 80 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 8 hour diastolic blood pressure from baseline diastolic blood pressure.

Secondary Outcome Measures :

1. Change in FFA (Free Fatty Acid) Levels From Baseline to 4 Hours [ Time Frame: Baseline, 4 hours ]
   Blood samples were collected for measurement of free fatty acids (FFA) at baseline and 4 hours after each infusion. FFA levels were determined by colorimetric method. Current guidelines identify normal range of FFA level as less than 0.72 mmol/L. Elevated plasma levels of FFA indicate a greater rate of insulin resistance. Change is the difference between 4 hour FFA levels from baseline FFA levels.
2. Changes in FFA (Free Fatty Acid) Levels From Baseline to 8 Hours [ Time Frame: Baseline, 8 hours ]
   Blood samples were collected for measurement of free fatty acids (FFA) at baseline and 8 hours after each infusion. FFA levels were determined by colorimetric method. Current guidelines identify normal range of FFA level as less than 0.72 mmol/L. Elevated plasma levels of FFA indicate a greater rate of insulin resistance. Change iis the difference between 8 hour FFA levels from baseline FFA levels.
3. Change in Triglyceride Levels From Baseline to 4 Hours [ Time Frame: Baseline, 4 hours ]
   Blood samples were collected for measurement of triglycerides at baseline and 4 hours after each infusion. Triglyceride levels were measured on CX7 Chemistry Analyzer. Current guidelines identify normal range of triglyceride level as less than 150 mg/dL. Elevated levels of triglycerides are associated with an increased risk of developing heart disease. Change is the difference between 4 hour triglyceride levels from baseline triglyceride levels.
4. Change in Triglyceride Levels From Baseline to 8 Hours [ Time Frame: Baseline, 8 hours ]
   Blood samples were collected for measurement of triglycerides at baseline and 4 hours after each infusion. Triglyceride levels were measured on CX7 Chemistry Analyzer. Current guidelines identify normal range of triglyceride level as less than 150 mg/dL. Elevated levels of triglycerides are associated with an increased risk of developing heart disease. Change is the difference between 8 hour triglyceride levels from baseline triglyceride levels.
5. Plasma Glucose Levels for Saline Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
   Blood samples were collected for measurement of plasma glucose levels at baseline, 4 hours after saline infusion, and 8 hours after saline infusion. Plasma glucose was measured on CX7 Chemistry Analyzer. Current guidelines identify normal fasting glucose as less than 100 mg/dL. High levels of glucose most frequently indicates diabetes.
6. Plasma Glucose Levels for Intralipid Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
   Blood samples were collected for measurement of plasma glucose levels at baseline, 4 hours after intralipid infusion, and 8 hours after intralipid infusion. Plasma glucose was measured on CX7 Chemistry Analyzer. Current guidelines identify normal fasting glucose as less than 100 mg/dL. High levels of glucose most frequently indicates diabetes.
7. Plasma Glucose Levels for Dextrose Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
   Blood samples were collected for measurement of plasma glucose levels at baseline, 4 hours after dextrose infusion, and 8 hours after dextrose infusion. Plasma glucose was measured on CX7 Chemistry Analyzer. Current guidelines identify normal fasting glucose as less than 100 mg/dL. High levels of glucose most frequently indicates diabetes.
8. Plasma Glucose Levels for Intralipid/Dextrose Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
   Blood samples were collected for measurement of plasma glucose levels at baseline, 4 hours after intralipid/dextrose infusion, and 8 hours after intralipid/dextrose infusion. Plasma glucose was measured on CX7 Chemistry Analyzer. Current guidelines identify normal fasting glucose as less than 100 mg/dL. High levels of glucose most frequently indicates diabetes.
9. Insulin Levels for Saline Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
   Blood samples were collected for the measurement of insulin levels at baseline, 4 hours after saline infusion, and 8 hours after saline infusion. Insulin was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal insulin levels as 8.8 μU/mL for men and 8.4 for women. High levels of insulin most frequently indicate insulin resistance or hypoglycemia, if paired with a low glucose level. Low levels of insulin paired with high glucose level can indicate diabetes.
10. Insulin Levels for Intralipid Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
    Blood samples were collected for the measurement of insulin levels at baseline, 4 hours after intralipid infusion, and 8 hours after intralipid infusion. Insulin was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal insulin levels as 8.8 μU/mL for men and 8.4 for women. High levels of insulin most frequently indicate insulin resistance or hypoglycemia, if paired with a low glucose level. Low levels of insulin paired with high glucose level can indicate diabetes.
11. Insulin Levels for Dextrose Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
    Blood samples were collected for the measurement of insulin levels at baseline, 4 hours after dextrose infusion, and 8 hours after dextrose infusion. Insulin was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal insulin levels as 8.8 μU/mL for men and 8.4 for women. High levels of insulin most frequently indicate insulin resistance or hypoglycemia, if paired with a low glucose level. Low levels of insulin paired with high glucose level can indicate diabetes.
12. Insulin Levels for Intralipid/Dextrose Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]
    Blood samples were collected for the measurement of insulin levels at baseline, 4 hours after intralipid/dextrose infusion, and 8 hours after intralipid/dextrose infusion. Insulin was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal insulin levels as 8.8 μU/mL for men and 8.4 for women. High levels of insulin most frequently indicate insulin resistance or hypoglycemia, if paired with a low glucose level. Low levels of insulin paired with high glucose level can indicate diabetes.
13. C-peptides Levels for Saline Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]

    Blood samples were collected for the measurement of C-peptide levels at baseline, 4 hours after saline infusion, and 8 hours after saline infusion. C-peptide was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal C-peptide levels as 0.51 to 2.72 ng/mL.

    A high level of C-peptide generally indicates a high level of endogenous insulin production. This may be in response to a high blood glucose caused by glucose intake and/or insulin resistance. A high level of C-peptide is also seen with insulinomas and may be seen with low blood potassium, Cushing syndrome, and renal failure. A low level of C-peptide is associated with a low level of insulin production. This can occur when insufficient insulin is being produced by the beta cells, with diabetes for example, or when production is suppressed by treatment with exogenous insulin.

14. C-peptides Levels for Intralipid Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]

    Blood samples were collected for the measurement of C-peptide levels at baseline, 4 hours after Intralipid infusion, and 8 hours after Intralipid infusion. C-peptide was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal C-peptide levels as 0.51 to 2.72 ng/mL.

    A high level of C-peptide generally indicates a high level of endogenous insulin production. This may be in response to a high blood glucose caused by glucose intake and/or insulin resistance. A high level of C-peptide is also seen with insulinomas and may be seen with low blood potassium, Cushing syndrome, and renal failure. A low level of C-peptide is associated with a low level of insulin production. This can occur when insufficient insulin is being produced by the beta cells, with diabetes for example, or when production is suppressed by treatment with exogenous insulin.

15. C-peptides Levels for Dextrose Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]

    Blood samples were collected for the measurement of C-peptide levels at baseline, 4 hours after dextrose infusion, and 8 hours after dextrose infusion. C-peptide was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal C-peptide levels as 0.51 to 2.72 ng/mL.

    A high level of C-peptide generally indicates a high level of endogenous insulin production. This may be in response to a high blood glucose caused by glucose intake and/or insulin resistance. A high level of C-peptide is also seen with insulinomas and may be seen with low blood potassium, Cushing syndrome, and renal failure. A low level of C-peptide is associated with a low level of insulin production. This can occur when insufficient insulin is being produced by the beta cells, with diabetes for example, or when production is suppressed by treatment with exogenous insulin.

16. C-peptides Levels for Intralipid/Dextrose Infusion [ Time Frame: Baseline, 4 hours, 8 hours ]

    Blood samples were collected for the measurement of C-peptide levels at baseline, 4 hours after intralipid/dextrose infusion, and 8 hours after intralipid/dextrose infusion. C-peptide was measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the DPC Immulite analyzer. Current guidelines identify normal C-peptide levels as 0.51 to 2.72 ng/mL.

    A high level of C-peptide generally indicates a high level of endogenous insulin production. This may be in response to a high blood glucose caused by glucose intake and/or insulin resistance. A high level of C-peptide is also seen with insulinomas and may be seen with low blood potassium, Cushing syndrome, and renal failure. A low level of C-peptide is associated with a low level of insulin production. This can occur when insufficient insulin is being produced by the beta cells, with diabetes for example, or when production is suppressed by treatment with exogenous insulin.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Males or females
• Obese subjects (body mass index (BMI) ≥ 30 kg/m^2)
• 18 and 65 years
• Blood pressure reading < 140/80 mm Hg and no prior history of hypertension

Exclusion Criteria:

• History of diabetes mellitus
• History of hypertension
• Fasting triglyceride levels > 250 mg/dL
• Liver disease (ALT 2.5x > upper limit of normal)
• Serum creatinine ≥1.5 mg/dL
• Smokers, drug or alcohol abuse
• Mental condition rendering the subject unable to understand the scope and possible consequences of the study
• Female subjects who are pregnant or breast feeding

Contacts and Locations

Locations

United States, Georgia

Grady Memorial Hospital

Atlanta, Georgia, United States, 30303

Sponsors and Collaborators

Emory University

American Diabetes Association

Investigators

• Principal Investigator: Guillermo Umpierrez, MD; Emory University

More Information

• Responsible Party: Guillermo Umpierrez, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT00721617
• Other Study ID Numbers: IRB00009277
• First Posted: July 24, 2008
• Results First Posted: July 27, 2015
• Last Update Posted: July 27, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

Hypertension; Inflammation; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Soybean oil, phospholipid emulsion; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions