Bezafibrate affects lipid, lipo- and apolipoprotein pattern in non-insulin-dependent diabetic patients.

To assess bezafibrate efficacy in a diabetic population a single-blind randomized study was performed in 32 diet-resistant type IIb hyperlipidaemic non-insulin-dependent (NID) diabetic patients in good metabolic control (HbA1c < 8%) compared to a placebo group. In our diabetic patients one month treatment of 400 mg/day bezafibrate lowered plasma C (-14%) and TG (-37%) and globally reduced the VLDL particles and VLDL lipids (-37% for C, -56% for TG and -25% for PL), raising VLDL C/TG ratio (+46%), redistributing TG from VLDL to LDL (+10%) and mainly in HDL (+49%), lowered LDL-C and Apo B levels and increased HDL-C together with Apo A1 (+19% and +13%) and Apo A1/Apo B (+72%). PL were raised by bezafibrate treatment and were redistributed from VLDL (-25%) to LDL (+25%) and HDL (+18%), while PL/C ratio increased in VLDL and in LDL (+18% and +50% respectively). Bezafibrate use was safe and improved the lipid pattern and the apolipoprotein and lipid distribution in the lipoproteins, producing a less atherogenic pattern in our NID diabetics.

Comparison of the effects of bezafibrate and acipimox on the lipid pattern and plasma fibrinogen in hyperlipidaemic type 2 (non-insulin-dependent) diabetic patients.

Correction of cardiovascular risk factors is of particular significance in a high-risk population, such as that of diabetic patients. This paper reports the effects of one-month administration of 400 mg/day Bezafibrate (BZF), followed by a two-month wash-out and one-month administration of 500 mg/day Acipimox (APX) or vice versa in a random order in 16 Type 2 diabetic patients with diet-resistant hyperlipidaemia and in good metabolic control (HbA1c less than 8%), on plasma fibrinogen and on their lipid pattern. Metabolic control displayed a nonsignificant improvement (HbA1c) during both treatments (stable body weight). Both BZF and APX produced a 14% decrease in total CHOL (p less than 0.01), whereas BZF was more effective in reducing triglycerides (tg) (-37% vs -15%). The marked BZF-induced Tg reduction was associated with a proportional decrease in Apo B, while an increase in total HDL-, HDL2 and HDL3-CHOL, together with a significant increase in Apo AI, was observed. APX treatment resulted in a HDL2-CHOL increase only (+29%). Both drugs reduced VLDL-CHOL (BZF -37%; APX -15%) and VLDL-Tg (-56% and -34%). In BZF treated patients Apo CIII fell indicating a possible reduction of specific inhibition of lipoprotein lipase activity, while APX affected both Apo CII (+23%) and Apo CIII (-26%) and led to a 62% Apo CII/CIII ratio increase. BZF alone led to a significant 25% decrease in plasma fibrinogen (from 415 +/- 14.3 to 312.1 +/- 18.1 SEM mg/dl, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[The role of plasma lipids and of coagulation factors in atherosclerosis. Clinical trials and new prospects]. / Ruolo dei lipidi plasmatici e dei fattori della coagulazione nell'aterosclerosi. Trial clinici e nuove prospettive.

The relevance that lipids have in the pathogenesis and progression of atherosclerotic lesions is well-known. In these last years further insight has come about the role of hemostatic factors in these processes. Plasma fibrinogen seems directly involved in the genesis of atherosclerotic plaque and in the modulation of endothelium/circulating-cells microenvironment. Epidemiological data show that fibrinogen is a major risk factor for cardiovascular death and ischemic heart, brain and peripheral vessels disease. In this review we considered current data about pathogenetic mechanisms of atherosclerosis and its complication in which hemostatic/hemorheological factors (plasma fibrinogen, factor VIIc, platelets and leucocytes) are involved as well as the prognostic relevance of these components in human vascular pathology. Current knowledge suggests the need for intervention both on altered plasma lipids and on altered hemostatic parameters. At present, the actual possibilities of pharmacological intervention in the second case, apart from antiplatelet agents, are really poor. Among the drugs till now employed, fibrates are considered with interest as they seem to ameliorate both pathogenetic mechanisms: bezafibrate lowers plasma total- and LDL-cholesterol, triglycerides as well as plasma fibrinogen and other hemocoagulative parameters. This drug might be proposed in at risk populations in order to reduce the incidence and prevalence of atherosclerotic complications: at present, unfortunately, longitudinal studies to confirm this therapeutic rationale are not available.

Effect of short-term treatment with bezafibrate on plasma fibrinogen, fibrinopeptide A, platelet activation and blood filterability in atherosclerotic hyperfibrinogenemic patients.

The effect of bezafibrate (BZF) on plasma fibrinogen levels has been studied in 62 patients with atherosclerotic vasculopathy and hyperfibrinogenemia (643 +/- 15 (SEM) mg/dl). In a preliminary study, 15-30 days of BZF therapy (400-600 mg/day) normalized fibrinogen values in 16 subjects were compared to 16 controls. The effect was rapid and dose-dependent, and discontinuation in 6 patients who could not complete the study was followed by a rebound increase. A controlled study with 400 mg/day in the other 24 patients for 15 days showed that BZF lowered fibrinogen, PF4, blood filterability and platelet aggregating thresholds to the normal range. BTG and FpA decreased significantly compared to the placebo group (12 and 12 patients randomly distributed) without any variation in potentially biassing hematologic values (WBC, PLTS, Ht, lipids and plasma glucose). BZF may be of value in chronic treatment of hyperfibrinogenemia in atherosclerotic patients with a view to improving the haemorheologic pattern and, hence, reducing activation of the coagulation pathway.

Effect of dehydroepiandrosterone on human erythrocytes redox metabolism: inhibition of glucose-6-phosphate dehydrogenase activity in vivo and in vitro.

In order to elucidate the role of G6PD inhibition by DHEA on erythrocyte redox metabolism, we measured: (1) G6PD activity in erythrocytes collected at different times after injection of synthetic ACTH in 13 normal subjects; (2) G6PD activity and GSH levels in erythrocytes incubated in the presence of different DHEA concentrations; (3) DHEA distribution and metabolic clearance in red cells, together with G6PD activity; (4) GSH regeneration after hydroperoxide oxidative stress in red cells preincubated in the presence of DHEA. In vivo DHEA increase elicits a clear-cut inhibition of red cell G6PD activity. Decreasing DHEA goes in step with the recovery of enzyme activity. In vitro G6PD inhibition by DHEA reaches its maximum within 10-15 min (20-25% inhibition at 10(-7) M DHEA concentration) and the recovery time is dose-dependent. More than 2/3 of DHEA is concentrated in the red cell after 5 min incubation. GSH levels change in step with G6PD activity. After oxidative stress by BHP, DHEA-treated cells fail to restore normal GSH concentrations. These results show that DHEA inhibits human erythrocyte G6PD activity at concentrations usually observed after ACTH plasma increase and increases red cell sensitivity to oxidant agents. Moreover, it is possible that the high DHEA concentrations present in target tissues may interfere with metabolic pathways in which NADPH is the cofactor.