title: Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome.
abstract: OBJECTIVE
  This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS.
  
  
  METHODS
  In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention.
  
  
  RESULTS
  By 12 weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP.
  
  
  CONCLUSIONS
  In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β-cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.
authors.affiliation: Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Aye
authors.forename: E S
authors.initials: ES
authors.lastname: Kilpatrick
authors.forename: P
authors.initials: P
authors.lastname: Afolabi
authors.forename: S A
authors.initials: SA
authors.lastname: Wootton
authors.forename: A S
authors.initials: AS
authors.lastname: Rigby
authors.forename: A M
authors.initials: AM
authors.lastname: Coady
authors.forename: D D
authors.initials: DD
authors.lastname: Sandeman
authors.forename: S L
authors.initials: SL
authors.lastname: Atkin
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage*; D050356:Lipid Metabolism / Q000187:drug effects*; D009525:Niacin / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D040242:Risk Reduction Behavior; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D014280:Triglycerides; D009525:Niacin
keywords: endothelial dysfunction; insulin resistance; niacin/laropiprant; polycystic ovary syndrome; triglycerides