Session: OR48-Insulin Resistance & Metabolic Syndrome: From Clinical Physiology to Clinical Care
Room 304 (Moscone Center)
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
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