[Obstructive sleep apnea and risk factors for coronary artery disease]. / Obturacyjny bezdech senny a czynniki ryzyka choroby niedokrwiennej serca.

STUDY AIM: Obstructive sleep apnoea (OSA) is strongly associated with obesity, especially abdominal obesity. Obesity in turn is a well-known risk factor for coronary artery disease (CAD). The aim of our study was to evaluate the relationship between OSA severity and CAD risk factors. MATERIAL AND METHODS: The sample consisted of 73 subjects (mean age +/- SE, 46.7 +/- 1 years) referred to a sleep laboratory. Subjects were either: 1. obese with OSA (O-OSA group n = 35; body mass index, BMI l 30 kg/m2; apnoea/hypopnoea index, AHI > 35), 2. non-obese with OSA (BO-OSA group n = 14; BMI < 27 kg/m2; AHI > 35), or 3. obese without OSA (O-Z group n = 24; BMI l 30 kg/m2; AHI < 5). All subjects underwent full overnight polysomnography. Blood samples were taken from all subject, for fasting levels of insulin (INS), glucose (GLU), total, HDL and LDL cholesterol, triglyceride (TG) and uric acid (UA). RESULTS: O-OSA had significantly higher INS and UA levels (p < 0.05) compared to BO-OSA and O-Z. GLU and lipid levels were comparable in the studied groups. GLU level correlated (p < 0.05) negatively to minimum oxyhemoglobin saturation (SAT-MIN) and positively to neck circumference. TG and UA levels were correlated (p < 0.05) positively to AHI and negatively to SAT-MIN. UA level was also positively correlated (p < 0.05) to BMI, waist/hip circumference ratio (WHR), and INS level. INS level correlated (p < 0.05) positively to AHI, T90, WHR and UA, and negatively to SAT-MIN and mean oxyhemoglobin saturation. After adjusting for the influence of OSA and obesity (multiple regression analysis), we found independent negative correlations (p < 0.05) between: GLU level and SAT-MIN, UA level and SAT-MIN, and INS level and SAT-MIN. An independent, positive correlation (p < 0.05) was found between TG level and AHI. CONCLUSIONS: Results of our study suggest that OSA increases the risk of coronary artery disease by increasing plasma levels of glucose, triglyceride and insulin, independent of obesity.

Relationship among leptin, neuropeptide Y, and galanin in young women and in postmenopausal women.

OBJECTIVE: To determine whether hormonal status may affect neuropeptide Y (NPY), galanin, and leptin release in postmenopausal women and in young women. DESIGN: Forty-eight postmenopausal women aged 47-65 years and 35 young women aged 26-39 years were investigated. RESULTS: Plasma leptin concentrations increased with increasing body mass index in both young and postmenopausal women and were significantly higher in obese postmenopausal women than in obese young women (p < 0.01). Plasma NPY levels in obese young and postmenopausal women were significantly higher than in lean women (p < 0.01 and p < 0.01, respectively) and were significantly higher in obese and nonobese postmenopausal women than in young women (p < 0.05 and p < 0.001, respectively). Plasma galanin levels in postmenopausal women, both lean and overweight, were significantly lower than in young women (p < 0.01 andp < 0.01, respectively). In obese postmenopausal women, plasma galanin concentrations were lower without differing significantly from those in obese young women. However, they were significantly higher than that in lean postmenopausal women (p < 0.001). CONCLUSIONS: Our results suggest that the differences is plasma leptin, NPY, and galanin between postmenopausal women and young women may be related to body mass index rather than to differences in hormonal status and that the higher NPY levels in both lean and obese postmenopausal women than in young women indicate that factors other than body mass index may be involved.

Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity.

AIM: It is commonly accepted that some neuropeptides play an important role in the control of appetite and hormonal secretion. Several gastrointestinal peptides may affect on central control of appetite via vagal and spinal nerves. The aim of this study was to evaluate the release of gastrointestinal peptides in anorexia nervosa and in obesity, because in these diseases the disturbances in the control of appetite and hormonal secretion were found. Material consisted of 30 women with anorexia nervosa aged 16-29 years (mean 22 years) and 23 women with obesity aged 19-33 years (mean 29 years) and 25 lean women of control group. METHODS: In women with anorexia nervosa as compared with control group we observed a significant increase of plasma vasoactive intestinal peptide (VIP) levels (p < 0.01) and a significant decrease of leptin (p < 0.001), beta-endorphin (p < 0.01), gastrin (p < 0.05), cholecystokinin (CCK; p < 0.05) and somatostatin (S-S; p < 0.01). In obese women we found a significant increase of neuropeptide Y (NPY; p < 0.001), leptin (p < 0.01), galanin (p < 0.001), beta-endorphin (p < 0.001), gastrin (p < 0.01), CCK (p < 0.001) and S-S (p < 0.01) and a significant decrease of VIP concentrations (p < 0.001) as compared with control group. CONCLUSION: Our results indicate that the release of gastrointestinal peptides is disturbed in obesity and in anorexia nervosa. These findings suggests that dysfunction of brain-gut axis may be also an important factor in the abnormal control of appetite axcept of hypothalamic dysfunction.

Neuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome.

It has been reported that polycystic ovary syndrome (PCOS) is very frequently associated with obesity, insulin resistance and hyperinsulinemia. However, metabolic disorders may lead to suppression of reproductive hormone secretion during undernutrition and in obesity. Some neuropeptides, such as neuropeptide Y (NPY) and galanin, modulate the control of appetite and play an important role in the mechanism of luteinizing hormone-releasing hormone (LHRH) secretion. NPY and galanin regulate appetite via both central and peripheral mechanisms. The interaction between central and peripheral signals for the control of food intake is due to leptin. Leptin can modulate the activity of NPY and other peptides in the hypothalamus that are known to affect eating behavior. In order to evaluate the relationship between NPY, galanin and leptin, 28 women with PCOS, 32 obese women (non-PCOS) and 19 lean healthy women (control group) were investigated. Obese women with PCOS were divided into two groups: PCOS (A) overweight (body mass index, BMI 26-30 kg/m2), and PCOS (B) obese (BMI 31-40 kg/m2). Plasma NPY, galanin and leptin concentrations were measured by radioimmunoassay. Plasma leptin levels in obese women with PCOS (groups A and B) were significantly higher than those in the control group (p < 0.05, p < 0.05, respectively). A significant positive correlation between plasma leptin and BMI in women with PCOS was found (r = 0.427, p < 0.01). A positive correlation was demonstrated between leptin and testosterone in PCOS (r = 0.461, p < 0.01). Plasma galanin concentrations in PCOS were higher than in the control group but the differences were not significant. Plasma NPY levels were significantly elevated in both non-obese (normal) and obese women with PCOS (group A) (p < 0.01, p < 0.005, respectively). However, in obese non-PCOS women plasma NPY levels gradually increased with increase in BMI. No significant correlations were found between galanin, NPY and percentage change in response of LH to LHRH, as well as between NPY and insulin, and galanin and testosterone. Plasma insulin concentrations in women with PCOS (group B) were significantly higher than in the control group (p < 0.001). Increased plasma NPY levels are found in both obese and non-obese women with PCOS. The increase in NPY is independent of the increase in BMI. In obese women with PCOS, plasma leptin is increased compared with control lean women. Serum insulin concentration is increased in obese women with PCOS. A positive correlation exists between leptin and BMI as well as between leptin and testosterone in women with PCOS. These results may suggest that the feedback system in the interaction between leptin and NPY is disturbed in PCOS.

Correlation between 21 amino acid endothelin, intrafollicular steroids and follicle size in stimulated cycles.

Several in-vitro studies have shown that endothelins (ET) may inhibit synthesis of progesterone and prevent luteinization of granulosa cells. In the present study, a specific radioimmunoassay was used to evaluate the correlation between concentrations of active (21 residue) ET and ovarian steroids in 47 samples of human follicular fluid (FF) following gonadotrophin stimulation for in-vitro fertilization (IVF) protocols. An isoform non-selective antibody was used in the radioimmunoassay, which recognized the C-terminal structure of the 21 residue ET, and therefore did not crossreact with their weakly active precursors - big ET. In pooled samples of follicular fluid (FF), the concentration of 21 amino acid ET correlated negatively with diameter of the follicles (r = -0.31, P < 0.05) and progesterone concentrations in FF (r = -0.56, P < 0. 001). A positive relationship (non-significant) was found between ET and testosterone concentrations. No correlation between ET and oestradiol was observed. The within-patient correlation coefficients were also evaluated in women from whom three or more samples of FF were obtained. ET were markedly inversely correlated with follicle size in all cases, and with progesterone in five of seven women. Five of seven patients also showed significant positive correlation of ET with testosterone. The results demonstrate clinical evidence that active ET play an important role in regulation of follicle development, especially in the inhibition of premature luteinization of granulosa cells.

Are mu-opioid receptors involved in the control of endothelin-1 release from the pituitary gland in normal and dehydrated rats?

UNLABELLED: The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS: (1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS: (1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.

Neuropeptide Y, galanin, and leptin release in obese women and in women with anorexia nervosa.

The study objective was to determine circulating levels of the appetite-controlling neuropeptides, neuropeptide Y (NPY), galanin, and leptin, in subjects with eating disorders. The study group consisted of 48 obese women aged 19 to 45 years, 15 women with anorexia nervosa aged 18 to 23 years, and 19 lean healthy women aged 18 to 42 years (control group). The obese women were divided into four groups: (A) body mass index (BMI) = 25 to 30 kg/m2, n = 9 (overweight); (B) BMI = 31 to 40 kg/m2, n = 23 (moderate obesity); (C) BMI greater than 40 kg/m2, n = 9 (severe obesity); and (D) BMI = 31 to 40 kg/m2, n = 7 (moderate obesity + non-insulin-dependent diabetes mellitus [NIDDM]). Plasma NPY, galanin, and leptin concentrations were measured in peripheral blood samples with radioimmunoassay methods. Plasma NPY levels in obese women (groups A, B, C, and D) were significantly higher as compared with the control group (P < .01, P < .001, P < .001, and P < .001, respectively). The highest plasma NPY concentrations were observed in obese women with NIDDM. Plasma galanin levels were significantly higher in groups B, C, and D (P < .001, P < .001, and P < .001, respectively). Plasma leptin concentrations were significantly higher in groups C and D as compared with the control group (P < .001 and P < .001, respectively). Plasma NPY and galanin concentrations in women with anorexia nervosa did not differ from the levels in the control group. However, plasma leptin concentrations were significantly lower in anorectic women than in the control group (P < .01). Our results indicate that inappropriate plasma concentrations of NPY, galanin, and leptin in obese women may be a consequence of their weight status, or could be one of many factors involved in the pathogenesis of obesity.

Impaired response of atrial natriuretic peptide to acute water load in obesity and in anorexia nervosa.

Plasma atrial natriuretic peptide (ANP) concentrations were determined in basal conditions and after infusion of 1000 ml of 0.9% NaCl in women with anorexia nervosa, in normotensive obese women and in healthy women of the control group. Additionally, in the obese women and in the controls, plasma ANP was measured after iv injection of clonidine. Anorectic patients were investigated in the period of weight loss (mean deficit of body weight was 40%). The mean body mass index (BMI) in the obese women was 36.44 +/- 0.36 kg/m2. Basal plasma ANP concentrations were significantly higher in both anorectic and obese women (p < 0.001 and p < 0.01, respectively). The response of ANP to acute water load was markedly blunted in anorexia nervosa and in obesity (delta % = 232% in control group, 14% in anorexia nervosa and 21% in obesity. A significant increase of ANP was found after iv injection of clonidine in the control group and in obesity (p < 0.001 and p < 0.01, respectively). However, the increase of response (expressed as a percentage change) in obese patients was lower than that in the control group (delta % = 64% and 199%, respectively). The response of ANP to alpha 2-adrenergic stimulation was higher than to hemodynamic stimulus. Our results suggest that the disturbed control of neuropeptides and neurotransmitters as well as changes in peripheral metabolism may explain the impaired responsibility of ANP to hemodynamic stimuli in anorectic and obese patients.

Prolactin and LH release in response to vasoactive intestinal peptide (VIP) administration in spontaneously hypertensive and normotensive rats.

UNLABELLED: Vasoactive intestinal peptide (VIP) was injected intravenously at a dose of 10 micrograms in spontaneously hypertensive and normotensive Wistar-Kyoto rats. In order to evaluate the hemodynamic and hormonal effects of this peptide, the mean arterial pressure, heart rate as well as a serum rLH and rPRL levels, the contents of LH-RH in hypothalamus and the content of LH in pituitary tissue were determined. The same procedure was applied in rats receiving placebo. Serum rPRL concentration was measured additionally after combined administration of VIP+dopamine. VIP injection produced a decrease in mean arterial pressure and an increase in heart rate in both spontaneously hypertensive and normotensive rats. Serum rPRL concentration was significantly increased at 10 minutes after injection. The combined therapy (VIP+dopamine) partially inhibited this response. Serum rLH concentration, the content of LH-RH in hypothalamic tissue as well as the content of pituitary LH after VIP injection in spontaneously hypertensive and normotensive rats did not differ from the values obtained for the control group. CONCLUSIONS: 1. VIP injection produced the dramatic hypotensive effects in hypertensive rats; 2. A marked increase in PRL concentration in response to VIP was partially inhibited by dopamine in hypertensive and normotensive rats; 3. VIP injection did not change LH-RH and LH release in both hypertensive and normotensive rats.