Pioglitazone improves the cardiovascular profile in patients with uncomplicated systemic lupus erythematosus: a double-blind randomized clinical trial.

OBJECTIVE: We studied the effect of pioglitazone on insulin levels, inflammation markers, high-density lipoprotein (HDL) composition and subclasses distribution, in young women with uncomplicated systemic lupus erythematosus (SLE). METHODS: This double-blind trial included 30 premenopausal women (30 ±8 years old) with SLE, who were randomized to pioglitazone (30 mg/day) or placebo treatment for 3 months. Plasma and HDL lipids were determined by colorimetric enzymatic assays, insulin by radioimmunometric assay, inflammation by immunonephelometry and HDL size and subclasses distribution by a native 4-30% polyacrylamide gradient gel electrophoresis. RESULTS: Compared with placebo, pioglitazone significantly increased HDL-cholesterol plasma levels (14.2%), reduced fasting insulin plasma levels (23.6%) and the homeostasis model assessment-insulin resistance (31.7%). C-reactive protein (70.9%) and serum amyloid A (34.9%) were also significantly reduced with the pioglitazone use, whereas the HDL particle size was increased (8.80 nm vs. 8.95 nm; p = 0.044) by changes in the distribution of HDL(2b), HDL(3b), and HDL(3c) subclasses. The change in HDL size correlated with a rise in free and cholesterol-ester content in the HDL particles. CONCLUSION: Pioglitazone significantly enhanced insulin sensitivity, reduced inflammation, and modified HDL characteristics, suggesting a potential beneficial effect of this drug in patients with SLE with a risk to develop cardiovascular disease. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov Protocol Registration System, with the number NCT01322308.

High-density lipoproteins are abnormal in young women with uncomplicated systemic lupus erythematosus.

Little is known about qualitative abnormalities of high-density lipoproteins (HDL) in systemic lupus erythematosus (SLE). We studied distribution and composition of HDL subclasses in 30 premenopausal women with uncomplicated SLE, and 18 controls matched for age and sex. Plasma and HDL lipids were determined by colorimetric enzymatic assays, HDL size distribution by native gradient polyacrylamide gel electrophoresis (PAGE) and apolipoproteins in HDL by sodium dodecyl sulphate denaturing PAGE. Compared with controls, SLE patients had significantly lower proportions of HDL(2b) (-14.7%) and higher proportions of HDL(3b) (+8.8%) and HDL(3c) (+23.3%). Cholesteryl ester (-18%) and apolipoprotein AI (-9%) were lower, whereas triglycerides (+32%) and apolipoprotein E (+27%) were higher in SLE HDL (P < 0.05; for all). In the whole population, stepwise regression analysis showed that only insulin concentrations (R(2) = 0.327) and plasma total apo AI (R(2) = 0.114) accounted independently to the variance in HDL size. This study shows that HDL distribution and composition are abnormal in non-complicated SLE patients. These HDL abnormalities have been reported to be associated to impaired atheroprotective properties of HDL and prevalence of coronary heart disease. Therefore, they may contribute to the premature atherosclerosis observed in young women with SLE.

[Effect of transdermal administration of 17-beta estradiol on the release of growth hormone by growth hormone liberating hormone (GH-RH-1-29) in climacteric women before and after treatment]. / Influencia de la administración transdérmica de 17-beta estradiol sobre la liberación de hormona de crecimiento mediante la hormona liberadora de la hormona de crecimiento (GH-RH-1-29) en mujeres climatéricas pre y postratamiento.

BACKGROUND: Great interest has sparked recently the role that plays the changes that the growth hormone undergoes in the menopausal woman, specially its involvement in the central nervous, cardiovascular, genitourinary, digestive and osteomuscular systems. OBJECTIVE: To evaluate the influence of transdermal administration of 17-beta estradiol on growth hormone secretion in menopausal women before and after treatment under the stimulus of growth-hormonereleasing hormone (GH-RH). MATERIAL AND METHODS: We studied 5 patients with a mean age of 51 +/- 4.1 yr. with clinical and biochemical evidence of menopause. Evolution time 5.4 +/- 4.61 (range: 1-13 yr.). We monitored the pulsatility of GH during the first 120 minutes and 3 hours after the administration of the GHRH-1-29-NH2, i.v. bolus (50 micrograms). There were obtained every 15 minutes for the determination of GH levels before and after the stimulus. Immediately thereafter hormone replacement therapy was initiated with transdermal beta-estradiol with 50 micrograms patches twice a week. Clinical evaluations and hormone dynamics with OHRH-1-29 were performed at baseline and at 1,3 and 6 months from the start of therapy as described previously. RESULTS: GH pulsatility before estrogen replacement therapy (ERT) in these 5 patients was: X: 0.48 +/- 0.22, 0.38 +/- 0.17, 0.45 +/- 0.25 and 0.29 (at baseline, 1, 3 and 6 months respectively) and 2.74 +/- o 1.21; 3.48 +/- 1.32 (p > 0.05) 4.91 +/- 1.57 (p < 0.05) and 6.04 +/- 1.69 (p < 0.05) (p in relation to baseline) post stimulus with GH-RH-1-29 at baseline 1, 3 and 6 months respectively after transdermal estrogen therapy. Gonadotrophins basal serum levels fall from X: 54.68 +/- 27 to 33.20 +/- 11.23 and 40.48 +/- 12 to 28.30 +/- 6.70 (FSH and LH respectively). Estradiol serum level were from 1.82 +/- 4.06 to 25.95 +/- 5.96 before and after treatment, respectively. COMMENTS AND CONCLUSIONS: These results demonstrate that transdermal estrogen therapy does not modify the pulsatility of growth hormone but it does increase the magnitude of response to the stimulus with GH-RH-1-29 proportional to the time of treatment. We consider that this tendency to increase the production of growth hormone could be explained by an endogenous deficit of growth hormone releasing hormone due to a number of factors including the lack of adequate estrogen serum levels in menopausal women. More investigations will be needed to support this hypothesis and to bring forth a new understanding of menopause and its treatment.