OR48-1 Acute hypertriglyceridaemia induces platelet hyperactivity that is not attenuated by insulin in PCOS a mechanism for enhanced cardiovascular risk?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR48-Insulin Resistance & Metabolic Syndrome: From Clinical Physiology to Clinical Care
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 9:15 AM
Room 304 (Moscone Center)
Myint M Aye*1, Ahmed Aburima2, Katie S Wraith2, Benjamin Spurgeon2, Derek Sandeman3, Eric S Kilpatrick4, Khalid M Naseem2 and Stephen L Atkin1
1Hull York Medical School, E Yorkshire, United Kingdom, 2University of Hull, Hull, United Kingdom, 3Southampton Univ Hosp, Southampton, United Kingdom, 4Hull and East Yorkshire NHS Trust, Hull, United Kingdom
Background: Atherothrombosis is associated with idiopathic platelet hyperactivity. Hypertriglyceridaemia and insulin resistance are both features of PCOS and are independent risk factors for cardiovascular disease (CVD). Here we examined the effect of induced hypertriglyceridaemia on insulin resistance and platelet function in medication naïve women with polycystic ovary syndrome (PCOS) and controls. In particular we focused on the possibility that endogenous platelet inhibitory pathways may be compromised as a mechanism for platelet hyperactivity.

Methods: Following a 12hr overnight fast, 13 PCOS and 12 healthy women had a 5hr infusion of saline and a 5hr infusion of 20% intralipid on consecutive days. In the last 2 hours of both infusions, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp. Platelet sensitivity to the agonist adenosine diphosphate (ADP) and antagonist prostacyclin (PGI2,) was measured by flow cytometry using whole blood taken during each infusion (2hrs) and at the end of each clamp (5hrs). Data were presented with mean± SD for age and body mass index (BMI) and median (IQR) for other parameters.

Results:  Age and BMI of controls and PCOS women were (24.1± 5.8 vs. 28.0± 6.3, p=0.13) year and (25.5± 5.0 vs. 29.7± 6.0, p=   0.07) kg/m2 respectively. When compared with saline, intralipid infusion increased triglycerides with subsequent decrease in insulin sensitivity (5.25 (3.3, 6.48) vs. 2.60 (0.88, 3.88) mg/kg/min p=<0.001) in controls and (3.15 (2.94, 3.85) vs. 1.06 (0.72, 1.43) mg/kg/min p=<0.001) in PCOS.  Platelet activation, measured by platelet fibrinogen binding and P selectin expression, at baseline was same in each group. Intralipid infusion for either 2h or 5h led to an increased propensity for platelet activation by ADP, but a hyporesponse to the platelet inhibitor PGI2 in both groups. We next examined platelet activation at the end of 5hr intralipid infusion both with and without insulin fusion. In controls insulin infusion reduced the platelet sensitivity e.g. percentage of platelets expressed fibrinogen binding to 1µM ADP ((78.7 (67.9, 82.3) vs. 62.8% (51.8, 73.3), p=0.02) and sensitivity to 0.01µM PGI2 increased (67.6 (39.5, 83.8) vs. 40.9% (23.8, 60.9), p=0.01) respectively, thereby abrogating the platelet hyperactivity caused by intralipid. In contrast, platelet response to ADP and PGI2 remained elevated (71.8 (58.7, 81.0) vs. 66.5% (56.3, 74.3), p=0.17) and diminished (34.9 (17.1, 50.9) vs. 31.8% (21.4, 45.4), p=0.38) respectively in PCOS.

Conclusions: Hypertriglyceridaemia caused platelet hyperactivity by increasing sensitivity to ADP, but decreasing sensitivity to the inhibitor PGI2. Platelet hyperactivity was reversed by insulin in control subjects but not those with PCOS, suggesting that hypertriglyceridaemia combined with insulin resistance may increase platelet activation and atherothrombotic risk.

Nothing to Disclose: MMA, AA, KSW, BS, DS, ESK, KMN, SLA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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