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 L.

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.

Citation

Aye, M. M., Kilpatrick, E. S., Aburima, A., Wraith, K. S., Magwenzi, S., Spurgeon, B., Rigby, A. S., Sandeman, D., Naseem, K. M., & Atkin, S. L. (2014). Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome. Journal of the American Heart Association, 3(1), https://doi.org/10.1161/JAHA.113.000706

• Journal Article Type: Article
• Acceptance Date: Dec 27, 2013
• Online Publication Date: Feb 28, 2014
• Publication Date: Jan 27, 2014
• Deposit Date: Jan 5, 2024
• Publicly Available Date: Jan 17, 2024
• Journal: Journal of the American Heart Association
• Print ISSN: 2047-9980
• Electronic ISSN: 2047-9980
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 1
• DOI: https://doi.org/10.1161/JAHA.113.000706
• Keywords: Hypertriglyceridemia; Insulin resistance; Intralipid; PCOS; Platelet activation
• Public URL: https://hull-repository.worktribe.com/output/4500793