Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects.

OBJECTIVES

To analyse the HDL associated anti-oxidant enzyme paraoxonase-1, during postprandial hyperlipaemia.

METHODS AND RESULTS

Type 2 diabetic patients (n=72), glucose intolerant patients (n=10) and controls (n=38) consumed a high fat:high carbohydrate meal. Blood samples were collected up to 4h and analysed for lipids and paraoxonase-1. In vitro studies examined HDL function with respect to the enzyme. There were significant postprandial increases in serum triglycerides. Paraoxonase-1 activity decreased significantly throughout the postprandial phase. Concentrations of the enzyme initially decreased significantly, but returned to fasting concentrations at 4h. Specific activities were significantly lower at 4h, compared to fasting. The decrease in specific activity was linked to the dynamic phase of postprandial lipoprotein metabolism. Apo AI limited loss of paraoxonase-1. HDL isolated after being subjected to postprandial conditions in vitro had reduced capacity to associate with and stabilise PON1.

CONCLUSIONS

Postprandial hyperlipaemia was associated with changes to serum paraoxonase-1, consistent with a reduced anti-oxidant potential of HDL. No differences were observed between diabetic and non-diabetic patients, suggesting that the effect was linked to postprandial hyperlipaemia. Modifications to paraoxonase-1 could contribute to increased risk of vascular disease associated with postprandial lipaemia, particularly in diabetic patients, who are already deficient in serum paraoxonase-1.