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

Pere Virgili Health Research Institute (IISPV)

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes Mellitus; Dyslipidemia

Treatments: Drug: Niacin plus laropiprant; Drug: Fenofibrate

Study type: Interventional

Funder types: Other

Identifiers

NCT02153879

IISPV-HUSJR-LOWHDL

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 30 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Fenofibrate

Experimental group

Description:

Fenofibrate 145 mg/day for 12 weeks

Treatment:

Drug: Fenofibrate

Niacin plus Laropiprant

Experimental group

Description:

Niacin 2g/day plus Laropiprant for 12 weeks

Treatment:

Drug: Niacin plus laropiprant