Background: Low high-density lipoprotein cholesterol (HDL-C) serum concentrations are independent risk factors for the development of coronary artery disease. In patients with the metabolic syndrome, low HDL-C can contribute to premature atherosclerosis. Extended-release (ER) niacin increases HDL-C and was shown to slow the progression of atherosclerosis. Adipose tissue is an important site of niacin action. Here we sought to determine potential pleiotropic effects of ER niacin on adipose tissue biology in patients with impaired glucose tolerance (IGT).
Methods and results: Thirty patients with IGT (mean age=45.2+/-3.9 years), low HDL-C serum concentrations (HDL-C <1.0 mmol/l), but no additional comorbidities were treated once-daily with ER niacin (1000 mg) in a randomized open-label controlled (n=30) study for 6 months. During the first 4 weeks, daily dose was increased from 375 to 1000 mg in weekly intervals. At baseline and after 6 months, subcutaneous adipose tissue biopsies were taken, body fat mass, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and adipokine serum concentrations were measured. After 6 months of ER niacin treatment, HDL-C increased significantly by 24% and adiponectin by 35%. In addition, ER niacin significantly reduced circulating lipoprotein (a) by 38% (p<0.001) and fasting triglycerides by 12% (p<0.05). Whole-body insulin sensitivity increased in the ER niacin treatment group, although this trend was not statistically significant (p=0.085). Six months ER niacin led to a significant reduction in mean adipocyte size associated with increased insulin sensitivity in isolated adipocytes and gene expression changes including increased adiponectin, C/EBPalpha, C/EBPdelta, PPARgamma and decreased carnitine palmitoyl transferase 2, hormone sensitive lipase, nicotinic acid receptor (GPR109B) and fatty-acid synthase mRNA expression.
Conclusion: Treatment with ER niacin significantly improves atherogenic lipid profile in patients with IGT. These beneficial effects could at least in part be due to pleiotropic niacin effects in adipose tissue, characterized by decreased mean adipocyte size, increased insulin sensitivity and altered mRNA expression profile.