Low Density Lipoprotein (LDL) Cholesterol Metabolism in Impaired Glucose Tolerance
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Impaired glucose tolerance Patients diagnosed with impaired glucose tolerance |
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.
Other Names:
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| Control Patients with normal blood glucose |
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Blood samples were used to determine the removal of the free and esterified cholesterol in impaired glucose tolerance patients. [day of test]
Eligibility Criteria
Criteria
Inclusion Criteria:
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total cholesterol < 6mmol/L
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LDL-C < 4mmol/L
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triacylglycerides < 2.2mmol/L
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with normal blood pressure or hypertension until 130/85 mmHg
Exclusion Criteria:
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presence of previous cardiovascular disease: macrovascular, peripheral arterial disease and cerebral stroke.
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presence of chronic disease: chronic renal failure (creatinin >30 ug/mg), hepatic failure, asthma, chronic obstructive pulmonary disease, inflammatory disease, oncology and thyropathy compensated.
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use of drugs: statins, fibrates, glucocorticoids and metformin
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Endocrinology Service and Lipid Laboratory of Heart Institute of University of São Paulo | São Paulo | Brazil |
Sponsors and Collaborators
- University of Sao Paulo General Hospital
- Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
- Principal Investigator: Antonio C Lerario, MD, pHD, University of São Paulo
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- LIPIDS-IGT