title: Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.
abstract: BACKGROUND
  Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS.
  
  
  RESULTS
  Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS.
  
  
  CONCLUSIONS
  Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk.
  
  
  BACKGROUND
  www.isrctn.org. Unique Identifier: ISRCTN42448814.
authors.affiliation: Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, UK.
authors.forename: Myint Myint
authors.initials: MM
authors.lastname: Aye
authors.forename: Eric S
authors.initials: ES
authors.lastname: Kilpatrick
authors.forename: Ahmed
authors.initials: A
authors.lastname: Aburima
authors.forename: Katie S
authors.initials: KS
authors.lastname: Wraith
authors.forename: Simbarashe
authors.initials: S
authors.lastname: Magwenzi
authors.forename: B
authors.initials: B
authors.lastname: Spurgeon
authors.forename: Alan S
authors.initials: AS
authors.lastname: Rigby
authors.forename: Derek
authors.initials: D
authors.lastname: Sandeman
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Naseem
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Atkin
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D004739:England; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000503:physiopathology; D015228:Hypertriglyceridemia / Q000097:blood*; D007333:Insulin Resistance; D015539:Platelet Activation; D010979:Platelet Function Tests; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides
keywords: PCOS; hypertriglyceridemia; insulin resistance; intralipid; platelet activation