Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia

Primary Outcome Measures:

• Evolution of non-esterified fatty acid and triglycerides concentrations over time [ Time Frame: After 42 and 56 days of placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]

  Twelve hours after ingestion of chronic treatment, measures of non esterified fatty acid and triglycerides concentrations were carried out during 480 minutes to assess acute and chronic treatment effect on lipolysis and on triglyceride concentration.

  To appreciate both acute and chronic effects, subjects received medicinal supplements in addition to their chronic treatment:

  • On day 42, 500 mg of placebo to assess chronic nicotinic acid effect versus placebo effect
  • On day 56, 500 mg of immediate-release nicotinic acid (INA) to assess acute versus chronic nicotinic acid effect.
  
  

Secondary Outcome Measures:

• Insulin sensitivity after treatment [ Time Frame: After 53 days of placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]
  Euglycemic Hyperinsulinemic clamp with glucose tracer infusion
  
  
• Lipoproteins metabolism [ Time Frame: After 53 days of placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]
  Stable Isotopic tracer infusion (d3-leucine, 13C-acétate, d5-glycerol)
  
  
• Lipid profile [ Time Frame: Before and after placebo or nicotinic acid treatment ] [ Designated as safety issue: No ]
  Measure of lipoproteins (VLDL, IDL, LDL, HDL) - characterization of lipoprotein's subfraction Measure of enzymatic activity of cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP) and lecithin cholesterol acyl transferase (LCAT)
  
  

24 patients will be included in a double blind placebo controlled cross-over 8 week study comparing placebo to Niaspan (a long release formulation of niacin). In order to prevent any drop out linked to the flushing side effect of niacin, patient will take aspirin (300mg) prior to treatment throughout the study duration. The study will include at start and end of each arm, a full lipoproteins quantification as well as a measure of enzymes involved in lipid metabolism. On day 42 and 56 of each period, after an administration of either placebo or 500mg of immediate release niacin respectively, changes in plasma free fatty acid levels will be measured for 8hours in order to assess potential loss of activity of niacin over time upon chronic treatment with niaspan. Half of the patient will have an exploration of their glucose metabolism using hyperinsulinic clamp technique, whereas in the other half a metabolic turnover study using stable isotopes will focus on their lipoproteins, triglycerides and cholesterol handling. These explorations will be done at the end of each treatment period.