The effect of atorvastatin therapy on lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein and the antioxidant paraoxonase.

OBJECTIVES: The aim of our study was to examine the influence of atorvastatin on lipid parameters, particularly on HDL, and on the activity of LCAT and CETP and how they affect the activity of the HDL-associated antioxidant enzyme paraoxonase. DESIGN AND METHODS: Thirty-three patients with types II.a and II.b primary hyperlipoproteinemia were enrolled into our study. The patients received atorvastatin, 20 mg daily, for 3 months. We measured the serum paraoxonase activity and concentration, oxidized LDL, LCAT and CETP activities. RESULTS: Atorvastatin significantly reduced the levels of cholesterol, triglyceride, LDL-C and apoB, while it did not influence the levels of HDL-C and apo A-I. The increases in serum PON-specific activity, PON/HDL ratio and LCAT activity were significant, while oxLDL and CETP activities were significantly decreased. CONCLUSION: Atorvastatin may influence the composition and function of HDL, thereby possibly increasing the activity of paraoxonase and preventing atherosclerosis.

Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance.

AIM: To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg). STUDY DESIGN: Cross-sectional case control study. RESULTS: Acylated ghrelin levels were significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p<0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups. CONCLUSION: Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.

Orlistat increases serum paraoxonase activity in obese patients.

BACKGROUND AND AIM: Previous studies have demonstrated that oxidative stress is increased in obese patients. The high-density lipoprotein (HDL) associated human paraoxonase 1 (PON1) can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Our objective was to assess the effects of orlistat therapy combined with diet on body mass index (BMI), waist circumference, lipid parameters, blood pressure, serum glucose level and PON1 activity. METHODS AND RESULTS: A longitudinal, multicenter, randomized study with and without orlistat treatment was performed. One hundred thirty nine otherwise healthy, obese subjects were divided in to two groups: 78 persons received orlistat (120 mg three times a day) combined with diet while 61 persons were kept on diet only. Anthropometrical parameters, serum lipid levels and PON1 activity were measured at baseline and after 6 months of treatment. BMI and waist circumference were reduced more pronouncedly in the orlistat group than in the control group. Patients receiving orlistat also had significantly greater improvements in fasting blood glucose levels and blood pressure. The orlistat-treated group showed a greater reduction in total cholesterol and triglyceride levels. In addition, the serum PON1 activity in these patients was significantly increased compared to the diet-only group. CONCLUSIONS: The 6-month treatment with orlistat had a beneficial effect on the lipid profile and improved the antioxidant status by increasing serum PON1 activity. However, because of the limited therapeutic effectiveness, obese patients with hypercholesterolemia should receive additional lipid lowering medications.

Ciprofibrate increases paraoxonase activity in patients with metabolic syndrome.

AIMS: Diabetic dyslipidaemia with decreased high-density lipoprotein-cholesterol (HDL-C) concentration plays a key role in enhanced atherosclerosis. The antioxidant effect of HDL is due to the influence of human paraoxonase 1 (PON1) and several authors have described decreased activity of this enzyme in Type 2 diabetics and subjects with metabolic syndrome. The goal of this study was to examine the effect of daily ciprofibrate on serum PON1 and lipoprotein concentrations in patients with metabolic syndrome. METHODS: Fifty-one patients with metabolic syndrome were enrolled into the study. We examined the effect of 100 mg day(-1) ciprofibrate treatment on lipid concentrations, oxidized low-density lipoprotein (LDL), PON1 concentrations and activity. We also investigated the calculated size of LDL-cholesterol (LDL-C). RESULTS: During the 3-month study, it was observed that following treatment with ciprofibrate, the serum triglyceride concentration decreased significantly (from 2.76 +/- 0.9 mmol l(-1) to 2.27 +/- 1.6 mmol l(-1); -18%; P < 0.001), while HDL-C increased significantly (from 0.95 +/- 0.2 mmol l(-1) to 1.2 +/- 0.3 mmol l(-1); 26%; P < 0.001). The oxidatively modified LDL-C concentration decreased significantly (from 137 +/- 19 U l(-1) to 117 +/- 20 U l(-1); P < 0.001), while HDL-associated apolipoprotein A1 significantly increased (from 1.35 +/- 0.2 g l(-1) to 1.75 +/- 0.3 g l(-1); P < 0.001). The LDL-C/LDL-apoB ratio, which reflects the size of LDL, increased significantly (from 0.96 +/- 0.05 to 1.05 +/- 0.06; P < 0.05). Serum PON1 activity was significantly elevated (from 108 +/- 34 U l(-1) to 129 +/- 31 U l(-1); P < 0.05), while standardized values for HDL-C remained significantly unchanged (PON1/HDL-C) (from 114 +/- 21 to 107 +/- 20; NS). CONCLUSION: Three months of treatment with ciprofibrate favourably affected the lipid profile, increased LDL resistance to oxidation and improved antioxidant status by increasing serum paraoxonase activity in these patients.

[Lipid-lowering therapy in patients with type-2 diabetes mellitus]. / Lipidszintcsökkentó terápia 2-es típusú diabetes mellitusban.

Diabetic dyslipidemia is mainly characterised by hypertriglyceridaemia, low HDL-cholesterol level, an increased small dense HDL concentration, i.e. by atherogenic dyslipidemia. Dyslipidaemia occurs in some two third of the type 2 diabetes cases. In the treatment of dyslipidaemia it is essential to control the diabetes, to reduce the intake of saturated fat and supplement it with monounsatured fat ty acid or complex carbohydrates. Based on the latest studies diabetes is considered the same risk as coronary heart disease and, therefore, diabetic dyslipidaemia should be treated in the same aggressive way. According to the simplified guidelines, after the diet--above 5.2 mmol/l cholesterol level--antilipaemic drugs, i.e. statin should be administered in order to achieve the primary goal of the therapy, namely the 2.6 mmol/l LDL-cholesterol level. In patients with combined II/b type hyperlipoproteinaemia statins are the drugs of first choice, fibric acid derivates being only considered in case of normal LDL-cholesterol level (< 3.4 mmol/l), if the HDL-cholesterol level is also low. Fibrate therapy is the first choice in the isolated hypertriglyceridaemia (> 2.3 mmol/l) as well as in type V. hyperlipoproteinaemia. On the basis of the guidelines far more patients with diabetes should be treated with lipid lowering therapy than before.