ENDO 2013

Acute Hypertriglyceridemia, Insulin Resistance, and Platelet Hyperactivity in PCOS

Recent study data suggests that acute, induced hypertriglyceridemia (HTG) increases platelet activation; however, this effect is not attenuated by insulin in women with PCOS as it is in healthy subjects.
Myint M. Aye, MRCP, at the Hull York Medical School in the United Kingdom, and colleagues reported their findings at ENDO 2013: The Endocrine Society’s 95th Annual Meeting & Expo in San Francisco on June 18, 2013.
According to the researchers, PCOS is commonly associated with metabolic syndrome, postprandial hypertriglyceridemia, insulin resistance (IR), and subsequent cardiovascular risks. IR is associated with platelet dysfunction, which plays a role in atherothrombosis. The authors aimed to evaluate the effects of induced, acute HTG and IR on platelet function in women with PCOS.
The study included 13 women with PCOS and 12 healthy women. As expected, the PCOS women were hyperandrogenic and insulin resistant when compared with controls. After an overnight fast, they received a 5 hour saline infusion. At 180 minutes, insulin sensitivity was measured using a hyperinsulinemic euglycemic clamp. Blood samples for platelet studies were collected at hours 2 and 5; platelet activation was measured by fibrinogen binding and P selectin expression in response to the agonist adenosine diphosphate (ADP) and antagonist prostacyclin (PGI2). This process was repeated one week later with a 5 hour infusion of 20% intralipid instead of saline.  
An increase in triglycerides (TGs) was seen in both groups (PCOS and healthy) as expected after lipid infusion when compared with saline infusion; subsequent insulin resistance was also seen in both groups (both p < 0.001). Intralipid infusion was associated with enhanced platelet response to ADP in both groups, resulting in increased platelet activation. However, the lipid infusion was associated with a continuation of platelet activity; it appeared to decrease the platelet’s ability to respond to PGI in both groups.
Next the investigators examined platelet activity in response to insulin infusion. In controls, platelet activation in response to ADP was decreased (78.7% vs. 62.8%, p = 0.02) after intralipid and insulin infusion, but sensitivity to PGI2 increased (67.6% vs. 40.9%, p = 0.01). Reversal of platelet activation with the addition of PGI2 occurred as expected, suggesting the platelets became more sensitive to PGI2 after the infusion of insulin. By contrast, in PCOS subjects, platelet response to ADP remained elevated (71.8% vs. 66.5%, p = 0.17), and platelet response to PGI2 remained diminished (34.9% vs. 31.8%, p = 0.38). Insulin was not associated with the ability of PGI2 to reverse platelet activation in women with PCOS.  
The intralipid infusion exacerbated IR in women with PCOS and induced IR in the healthy controls. It was also associated with increased platelet activation and decreased sensitivity to inhibitor PGI2 in both groups. In control subjects, the increase in platelet activation was reversed by insulin; however, this result was not seen in PCOS subjects. The researchers concluded that acute HTG and IR may increase cardiothrombotic risk through platelet activation in PCOS.  
The authors have no conflicts to disclose.

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