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Completed

NCT Number: NCT00738023

Free Fatty Acid-Induced Hypertension in Obese Subjects With Type 2 Diabetes

Insulin resistance has been implicated as the central pathogenetic feature of cardiovascular risk factor cluster that includes hypertension, impaired glucose tolerance, diabetes, dyslipidemia, and hemostatic disorders. Recent evidence suggests that increased levels of free fatty acids (FFA) in obese subjects is a leading candidate in the pathogenesis of insulin resistance (1-4). In our preliminary studies on the effect of FFA on insulin secretion and action (lipotoxicity), we have observed that the infusion of Intralipid/heparin to increase FFA ~ four-fold-baseline levels for 48 hours results in a significant and reproducible raise in systolic and diastolic blood pressure (BP) in obese African American subjects with and without diabetes. The increase in blood pressure is apparent after 12 hours of infusion, reaching a peak increment of 32 mm Hg in systolic and 14 mm Hg in diastolic pressure at 24 hours. These preliminary findings indicate that, in addition to the well-known effect on insulin resistance, sustained elevation of FFA results in the development of an acute metabolic syndrome.

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Key information

Conditions

Type 2 Diabetes Cardiovascular Diseases Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Hypertension Metabolic Diseases Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

About this study

The FFA-induced hypertension constitutes a useful model with which to examine disease mechanisms and test new therapeutic interventions to correct the different disorders associated with insulin resistance and metabolic syndrome. The effect of FFA on insulin action is well established (4-6); however, the pressor effect of FFA infusion in obese subjects has not been investigated. We hypothesize that observed changes in blood pressure is the result of acute endothelial dysfunction due to increased FFA concentration; and that rosiglitazone, a PPAR gamma receptor agonist, will protect against FFA-induced elevation in blood pressure and endothelial dysfunction in obese subjects.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Males or females between the ages of 18 and 70 years.
  • Subjects must have a BMI of ≥ 30 kg/m2.
  • Subjects must have a BP < 130/80 mm Hg and no prior history of hypertension.
  • A known history of type 2 diabetes mellitus < 3 years (now 5 years).
  • Subjects must have an HbA1c of < 9%.
  • Diabetic subjects must have been receiving as their only current anti-diabetic therapy stable doses of sulfonylureas for the last 2 months.
  • Subjects must be able to understand and willing to adhere to the study protocol.

Exclusion criteria

  • Subjects with history of hypertension (BP > 140/90 mm HG) or who have received antihypertensive drug therapy prior to the study.
  • Obese nondiabetic controls with impaired glucose tolerance (2-hour glucose between 140 - 199 mg/dl) during a 75-g OGTT.
  • Diabetic subjects who require insulin therapy or have received an insulin sensitizer agent (metformin, rosiglitazone, pioglitazone) within 3 months of entering the study (at SV1, week-2).
  • Subjects with fasting triglyceride levels > 250 mg/dL prior to the study (at SV1, week-2).
  • Clinically relevant hepatic disease (ALT 2.5x > upper limit of normal), or other significant medical or surgical illness.
  • Renal failure, as shown by a serum creatinine ≥1.5 mg/dL for males, or ≥ 1.4 mg/dL for females.
  • Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
  • Female subjects are pregnant or breast feeding at time of enrollment into the study.

Treatment and study plan

rosiglitazone

Drug

Diabetic subjects will be receive rosiglitazone for 6 weeks

normal saline 0.9%

Drug

Normal saline 0.9% intravenous infusion at 40ml/hr for 48 hours

Intralipid 20%

Drug

Intralipid 20% at 40ml/hr intravenously for 48 hours

Primary outcomes

  1. Changes in Systolic Blood Pressure During Initial Intralipid Infusion

    Time frame: Baseline, 48 hours

    Systolic blood pressure change from baseline during an 48-hour intralipid infusion

Secondary outcomes

  1. Changes in Systolic Blood Pressure During Saline Infusions

    Time frame: 48 hours

    Systolic blood pressure change from baseline during an 48-hour normal saline infusion in obese diabetic subjects

  2. Changes in Systolic Blood Pressure During Intralipid Infusion Post-rosiglitazone Intervention

    Time frame: 48 hours

    Systolic blood pressure change from baseline during an 48-hour intralipid infusion after taking rosiglitazone for 6 weeks in obese diabetic subjects

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • GlaxoSmithKline

Registry information

Important dates

Study start
2004
Primary completion
2009
Study completion
2009
First posted
Aug 20, 2008
Registry last updated
Dec 30, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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