Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia
Metabolic Effects of an 8 Week Niaspan Treatment in Patients With Abdominal Obesity and Mixed Dyslipidemia
Nicotinic acid (Niacin) has been used for many years for the treatment of dyslipidemia.
 Indeed Niacin decreases triglycerides (TG) and low density lipoprotein cholesterol (LDL-c)
 but more importantly increases high density lipoprotein cholesterol (HDL-c). Although the
 drug has been used for so long, its precise mechanism of action remains elusive. The aim of
 this study was to characterise the metabolic changes induced by 8 week treatment with Niacin
 in dyslipidemic, overweight patients. The importance of the inhibition of lipolysis on the
 overall lipid effects of niacin will be studied. In order to get a very comprehensive view of
 all metabolic activities of niacin, this study will investigate the potential effects of
 niacin on Glucose metabolism, lipid and lipoprotein turnover, quantitative changes in
 lipoproteins and key enzymes involved in lipid metabolism.
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.
Inclusion Criteria:

 -  Waist circumference > 94cm

 -  Triglyceride concentration between 150mg/dL and 400mg/dL

 -  HDL-c < 60mg/dL

 -  Body mass index: 27 to 35 kg/m²

 Exclusion Criteria:

 -  cancer

 -  diabetes mellitus

 -  hepatic, renal or digestive disorder

 -  hypertension

 -  chronic medical treatment interfering on lipids parameters