Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

Myint Myint Aye, Eric S. Kilpatrick, Ahmed Aburima, Katie S. Wraith, Simbarashe Magwenzi, B. Spurgeon, Alan S. Rigby, Derek Sandeman, Khalid M. Naseem, Stephen Atkin

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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. 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. 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. www.isrctn.org. Unique Identifier: ISRCTN42448814.

Original languageEnglish
JournalJournal of the American Heart Association
Volume3
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Hypertriglyceridemia
Polycystic Ovary Syndrome
Insulin Resistance
Blood Platelets
Epoprostenol
Insulin
Platelet Activation
Adenosine Diphosphate
Lipids
Aptitude
Glucose Clamp Technique
P-Selectin
Fibrinogen
Fasting
Triglycerides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome. / Aye, Myint Myint; Kilpatrick, Eric S.; Aburima, Ahmed; Wraith, Katie S.; Magwenzi, Simbarashe; Spurgeon, B.; Rigby, Alan S.; Sandeman, Derek; Naseem, Khalid M.; Atkin, Stephen.

In: Journal of the American Heart Association, Vol. 3, No. 1, 2014.

Research output: Contribution to journalArticle

Aye, Myint Myint ; Kilpatrick, Eric S. ; Aburima, Ahmed ; Wraith, Katie S. ; Magwenzi, Simbarashe ; Spurgeon, B. ; Rigby, Alan S. ; Sandeman, Derek ; Naseem, Khalid M. ; Atkin, Stephen. / Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome. In: Journal of the American Heart Association. 2014 ; Vol. 3, No. 1.
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abstract = "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. 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. 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. www.isrctn.org. Unique Identifier: ISRCTN42448814.",
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AU - Wraith, Katie S.

AU - Magwenzi, Simbarashe

AU - Spurgeon, B.

AU - Rigby, Alan S.

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AU - Naseem, Khalid M.

AU - Atkin, Stephen

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