Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women

The paraoxonase (PON1) enzyme is associated with high-density lipoproteins (HDL) in the blood and is low in patients with type 2 diabetes. Hormone-rep lacement therapy (HRT) can increase HDL cholesterol levels, but its effect on serum PON1 arylesterase activity is uncertain. The aim of the present st udy was to determine the effect of 6 months' HRT with conjugated equine est rogen and medroxyprogesterone acetate on serum PON1 arylesterase activity i n postmenopausal women with type 2 diabetes. Serum PON1 activity was measur ed immediately before and at the end of the second arm of a randomized, pla cebo-controlled, crossover with washout study originally designed to test t he effect of HRT on plasma lipids in diabetic postmenopausal women. Baselin e serum PON1 arylesterase activity was significantly (P <.001) lower in the postmenopausal diabetic women (149 +/- 38 <mu>mol/mL/min; n = 47) than val ues in healthy postmenopausal women (173 +/- 32 mu mol/mL/min; n = 51). Ser um PON1 activity increased (10%) significantly (P =.009) in diabetic women treated with HRT compared with placebo. A significant (P =.02) interaction between baseline PON1 activity and treatment indicated a greater increase i n PON1 activity during HRT in women with lower baseline activities. At base line, serum PON1 arylesterase activity was correlated significantly with pl asma HDL cholesterol levels in diabetic women (r = 0.333, P =.01, n = 47), and the increase in serum PON1 activity was correlated significantly with t he change in plasma HDL cholesterol during HRT (r = 0.659, P =.0001, n = 28 ). These data suggest that serum PON1 activity is abnormally low in postmen opausal women with type 2 diabetes and increases during HRT, particularly i n women with lower baseline levels and in those who show a concomitant incr ease in HDL cholesterol Copyright (C) 2001 by W.B. Saunders Company.