Characterization of High Density Lipoprotein (HDL) in Type 2 Diabetes (T2D) After Fenofibrate or Niacin Treatment

Study Overview
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Brief Summary
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The structural and functional alterations of high density lipoproteins (HDL) levels in type 2 diabetes (T2D) patients linked to hypertriglyceridemia, hyperglycemia, insulin resistance, inflammation and oxidation, play a major role in the increased macrovascular risk in these patients. An impaired function of the adipose tissue (AT) in T2D contributes to low HDL concentrations. Objectives: 1) Quantitative and qualitative characterisation of HDL subclasses by ultracentrifugation, proteomic and metabolomic techniques. 2) To study the relationship between the HDL subclasses, preβ1 HDL and remnant HDL, and clinical determinants of arteriosclerosis. 3) Functional in vitro studies of the HDL subclasses determined in Objective 1. 4) To study the role of AT determining the low HDL levels. 5) To study the impact of HDL increasing drugs on HDL qualitative changes.

Detailed Description
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Groups of subjects: a) Diabetic patients with low HDL; b) Non-diabetic patients with low HDL; c) Diabetic patients with normal HDL levels; and d) Non-diabetic patients with normal HDL levels. The studies will be performed after washing out lipid lowering drugs. Intima media thickness (IMT) will be performed in all groups. Main biochemical techniques will be centralised. Isolation and characterisation of HDL subclasses and remnant HDL, as well as a determination and preβ1 HDL will be performed. HDL studies examining HDL proteomic and metabolomic profiles will be performed. Functional studies will determine the effects on the endothelium, inflammation, cholesterol efflux and oxidation according the qualitative changes. These HDL measurements will be repeated in group (a), after they are treated with fibrates or Niacin. HDL metabolism in adipocytes will be extensively studied, and the clinical associations between HDL alterations and plasma AT-derived molecules will be examined.

Official Title
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Qualitative and Quantitative Characterization of HDL in T2D After Fenofibrate or Niacin Treatment in Spanish Population

Conditions
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Type 2 Diabetes Mellitus, Dyslipidemia

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: Niacin plus laropiprant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetic patients Age from 30 years to 70 years HDL not exceeding 50 mg/dl in men or 60 mg/dl in women Exclusion Criteria: to be a smoker To be diagnosed with diabetes less than three months before To have triglyceride levels above 400 mg/dl Glycated hemoglobin higher than 9% Albuminuria above 300 mg/mg creatinine Chronic kidney disease (eFGR <30 ml/min/1.73 m2) Advanced retinopathy Neuropathy Cardiovascular disease in the last three months Chronic liver insufficiency Neoplastic disease or any chronic or incapacitating disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenofibrate<br>Fenofibrate 145 mg/day for 12 weeks | Drug: Fenofibrate<br>* fenofibrate 145/day for 12 weeks<br>* Other names: Secalip;|
| Experimental: Niacin plus Laropiprant<br>Niacin 2g/day plus Laropiprant for 12 weeks | Drug: Niacin plus laropiprant<br>* Niacin 2 g/day plus Laropiprant for 12 weeks<br>* Other names: Tredaptive;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDL particles size and number assessed by nuclear magnetic resonance (NMR) and reported as nm and micromol/L | HDL particles were studied by NMR in T2D patients after treatment with fenofibrate or Niacin | Two periods of 12 weeks treatment according to crossing over design | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apolipoprotein A1 (Apo A1), apolipoprotein A2 (Apo A2), paraoxonase (PON) HDL concentration (g/l - mg/l) | Apoprotein and antioxidant enzymes composition of HDL were also measured | Two periods of 12 weeks treatment according to crossing over design | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDL, Niacin, Fenofibrate, Diabetes, Metabolomics