Cholesterol Metabolism and Lipid Transfer in Diabetes

• ClinicalTrials.gov Identifier: NCT01010035
• Recruitment Status: Completed
• First Posted: November 9, 2009
• Last Update Posted: November 9, 2009
• Sponsor: University of Sao Paulo General Hospital
• Collaborator: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Information provided by: University of Sao Paulo General Hospital

Study Description

Brief Summary:

The diabetic dyslipidemia is one of the most important risk factor in the development of coronary artery disease. The low density lipoprotein (LDL)-like nanoemulsions is being used to study the clearance of cholesteryl ester and free cholesterol from intravascular in patients with advanced coronary artery disease and it was shown a higher removal of free cholesterol and higher deposit in vases of this patients. The aim of this study is to analyze the plasma kinetics of both forms of cholesterol(free ad esterified) in type 2 diabetes patients without a previous history of cardiovascular disease.

Condition or disease	Intervention/treatment
Type 2 Diabetes Mellitus	Other: Plasma kinetic study

Detailed Description:

Hypercholesterolemia is not typical of type 2 diabetes mellitus dyslipidemia, but alterations in LDL may occur related to atherogenesis.Cholesterol exist in two main forms in organism: free cholesterol and the esterified cholesterol. An artificial model to study this two forms of cholesterol is the use of LDL-like nanoemulsion doubly labeled with 14C-cholesteryl esters and 3H- cholesterol. This nanoemulsion is made without protein and when in the intravascular compartment it is able to acquires apolipoproteins from others lipoproteins, such apos A's, C's and E. This model allowed us to use the nanoemulsion particle as a probe to study the lipoproteins receptor binding and the cholesterol esterification process.

Study Design

• Study Type: Observational
• Actual Enrollment: 26 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Plasma Kinetics Study of Free Cholesterol and Cholesteryl Ester in Type 2 Diabetes Mellitus Patients
• Study Start Date: September 2006
• Actual Primary Completion Date: January 2009
• Actual Study Completion Date: May 2009

Groups and Cohorts

Group/Cohort	Intervention/treatment
type 2 diabetes; patients with diagnosis of Type 2 diabetes mellitus	Other: Plasma kinetic study; this study is done with the injection of LDL-like nanoemulsion doubly labeled with 14C- cholesteryl oleate and 3H- cholesterol, with a total radioactivity injection dose of 0.03mSV. Blood sample collected in a pre established period of time in 24 hours.; Other Name: LDL-like nanoemulsion
Control; non type 2 diabetes mellitus	Other: Plasma kinetic study; this study is done with the injection of LDL-like nanoemulsion doubly labeled with 14C- cholesteryl oleate and 3H- cholesterol, with a total radioactivity injection dose of 0.03mSV. Blood sample collected in a pre established period of time in 24 hours.; Other Name: LDL-like nanoemulsion

Outcome Measures

Primary Outcome Measures :

1. to identify the removal of the free and esterified cholesterol in type 2 diabetes patients [ Time Frame: day of test ]

Biospecimen Retention:   Samples Without DNA

whole blood samples

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

outpatient of the endocrinology clinics of Hospital das clinicas of University of São Paulo Medical school

Criteria

Inclusion Criteria:

• without a previous cardiovascular disease
• if arterial hypertension, or in use of antihypertensive drugs- it must be well controled with a systolic Blood pressure level <130mmHg and diastolic <85mmHg.
• total cholesterol < 6 mmol/L
• LDL- cholesterol <4 mmol/L

Exclusion Criteria:

• use of drugs- statins, fibrates, glucocorticoids, thiazolidinediones
• nephropathy- the presence of microalbuminuria(ratio of microalbuminuria/creatinin >30 ug/mg) or serum creatinin above 98umol/L in woman and above 115 umol/L in man
• retinopathy
• neuropathy presence of chronic disease: heart failure, chronic obstructive pulmonary disease, inflammatory disease and cancer

Contacts and Locations

Locations

Brazil

Endocrinology service and Lipid laboratory of Heart Institute of University of São Paulo

São Paulo, Brazil, 05423000

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

More Information

Publications:

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.

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.

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.

• Responsible Party: Antonio Carlos Lerario/ MD, PhD, university of são Paulo
• ClinicalTrials.gov Identifier: NCT01010035
• Other Study ID Numbers: LIPIDSDM
• First Posted: November 9, 2009
• Last Update Posted: November 9, 2009
• Last Verified: November 2009

Keywords provided by University of Sao Paulo General Hospital:

type 2 diabetes mellitus; dyslipidemia; kinetics

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases