Low Density Lipoprotein (LDL) Cholesterol Metabolism in Impaired Glucose Tolerance

Impaired Glucose Tolerance Clinical Trial

Official title:

Plasma Kinetics Study the of Free Cholesterol and Cholesterol Ester in Subjects With Impaired Glucose Tolerance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01020578
• Other study ID #: LIPIDS-IGT
• Status: Completed
• Phase: N/A
• First received: November 24, 2009
• Last updated: November 24, 2009
• Start date: June 2008
• Est. completion date: October 2009

Study information

• Verified date: November 2009
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Observational

Clinical Trial Summary

Impaired glucose tolerance is associated with an increased risk of developing cardiovascular disease and atherosclerosis for reasons not yet totally understood. Previous studies evaluated the kinetics of plasma LDL and a faster removal rate of free cholesterol in normolipidemic patients with diagnosed arterial coronary disease and deposits of this cholesterol on the blood vessel walls. This disassociation of the cholesterol may suggest a new mechanism for not only the genesis but for the progression of arterial coronary disease. The objective of this research was to study the plasma kinetics of free cholesterol and cholesterol ester in impaired glucose tolerance patient, asymptomatic for coronary artery disease (CAD), to elucidate mechanisms involved in atherogenesis in these patients.

Description:

Along with hyperglycemia, the presence of obesity and dyslipidemia, risk factors associated with the natural onset of diabetes mellitus type 2, could possibly explain the high susceptibility of the glucose intolerance to cardiovascular disease. Dyslipidemia commonly linked to glucose intolerance is characterized by hypertriglyceridemia, low HDL-C and in spite of the LDL-C being apparently normal or slightly elevated, there is presence of small dense LDL. Formulated in the laboratory, an artificial lipid nanoemulsion marked with both 14C-cholesterol ester and 3H-cholesterol with lipid composition similar to LDL allows study the plasma kinetics of the two forms of cholesterol (free and esterified. The nanoemulsion mimics the natural LDL, but is prepared without protein. In contact with the bloodstream, the nanoemulsion acquires apolipoproteins, apo E preferentially, allowing it to be recognized and removed from plasma by LDL receptor. The application of this nanoemulsion was shown to be technically safe, appropriate and simple to be used in humans in order to understand the role of dyslipidemia in the atherogenic process.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: October 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

• total cholesterol < 6mmol/L

• LDL-C < 4mmol/L

• triacylglycerides < 2.2mmol/L

• with normal blood pressure or hypertension until 130/85 mmHg

Exclusion Criteria:

• presence of previous cardiovascular disease: macrovascular, peripheral arterial disease and cerebral stroke.

• presence of chronic disease: chronic renal failure (creatinin >30 ug/mg), hepatic failure, asthma, chronic obstructive pulmonary disease, inflammatory disease, oncology and thyropathy compensated.

• use of drugs: statins, fibrates, glucocorticoids and metformin

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Glucose Intolerance
• Impaired Glucose Tolerance

Intervention

Other:
• Plasma kinetic study
This study is done with the injection of an artificial lipid nanoemulsion doubly labeled with 14C-cholesteryl oleate and 3H-cholesterol, with a total radioactivity injection dose of 0.03mSV. Blood samples collected in a pre established period of time in 24 hours.

Locations

Country	Name	City	State
Brazil	Endocrinology Service and Lipid Laboratory of Heart Institute of University of São Paulo	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

Couto RD, Dallan LA, Lisboa LA, Mesquita CH, Vinagre CG, Maranhão RC. Deposition of free cholesterol in the blood vessels of patients with coronary artery disease: a possible novel mechanism for atherogenesis. Lipids. 2007 May;42(5):411-8. Epub 2007 Apr 19. — View Citation

Santos RD, Chacra AP, Morikawa A, Vinagre CC, Maranhão RC. Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: effects of simvastatin. Lipids. 2005 Jul;40(7):737-43. — View Citation

Santos RD, Hueb W, Oliveira AA, Ramires JA, Maranhão RC. Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease. J Lipid Res. 2003 Mar;44(3):464-9. Epub 2002 Dec 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood samples were used to determine the removal of the free and esterified cholesterol in impaired glucose tolerance patients.		day of test	No