Katarzyna Dunajska

Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and cardiovascular risk factors in middle-aged men.

Adiponectin, an adipocyte-derived protein, seems to be a link between obesity, insulin resistance, and atherosclerosis. The present study investigated the association between adiponectin and coronary artery disease in middle-aged men. Material and methods: We examined 48 men (aged 40–60) with angiographically confirmed coronary atherosclerosis and 19 healthy men, matched by age, as a control group. Concentrations of glucose and lipids were estimated with enzymatic methods. Plasma level of adiponectin, total and free testosterone, estradiol, estrone, DHEA-S, and insulin were estimated with RIA commercial kits. Results: Men with coronary atherosclerosis had lower plasma adiponectin level than controls (16.2±9.2 vs 20.5±6.7 µg/mL; p<0.05). However, after including BMI and waist as covariate data in ANCOVA, the difference in adiponectin levels between men with CAD and controls lost statistical significance (respectively for BMI and waist: p=0.4 and p=0.7). Moreover, although not significant, adiponectin levels decreased as a function of the number of significantly narrowed coronary arteries. In a priori comparison the lowest adiponectin plasma concentration was in men with three-vessel coronary artery disease (14.3±9.8 µg/mL) and the highest in controls (20.5±6.8 µg/mL; p=0.09). Adiponectin plasma level correlated negatively (p<0.05) with BMI, waist, percentage of total fat, fasting-insulin-resistance index (FIRI), total cholesterol and triglycerides, and positively with quantitative insulin sensitivity check index (QUICKI), HDL cholesterol, total testosterone, and total testosterone/estradiol ratio. Conclusions: Our data suggest that low plasma adiponectin level is connected with insulin resistance syndrome and atherogenic lipid profile. It seems that adiponectin plays a role in pathogenesis of coronary atherosclerosis, especially in obese and insulin-resistant subjects.

The vitamin D receptor gene BsmI polymorphism is not associated with anthropometric and biochemical parameters describing metabolic syndrome in postmenopausal women

Aim. Vitamin D could have a direct effect on adipocyte differentiation and metabolism and might be involved in glucose regulation of insulin secretion. In recent years several polymorphisms in the gene encoding the vitamin D receptor (VDR), which are potent to alter the activity of VDR protein, have been described. The present study aimed to investigate the prevalence of the VDR BsmI polymorphism and its association with anthropometric and biochemical features of metabolic syndrome in postmenopausal women. Materials and methods. We studied 351 randomly selected healthy postmenopausal women, with mean age of 55.43 ± 2.75 years and mean body mass index (BMI) of 27.5 ± 4.78 kg/m2, to evaluate the frequency of BsmI polymorphism (by restriction fragment length polymorphism–polymerase chain reaction) in the VDR gene and to find out whether there is an association between this polymorphism and BMI, total fat volume and visceral fat (as determined by total body dual-energy X-ray absorptiometry), blood pressure, lipid profile (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides) glucose and fasting insulin in the whole group, as well as subgroups of obese and non-obese women. Results. The prevalence of BsmI genotypes in the study group was 51.0% Bb, 37.3% bb and 11.7% BB. Genotype distribution did not differ from that expected under Hardy–Weinberg equilibrium conditions (χ2 = 2.95, p = 0.22). Apart from LDL-C levels (F = 3.46, p = 0.032), there were no significant differences in anthropometric or metabolic parameters between genotypes. Conclusions. The BsmI polymorphism in the VDR gene does not seem to predispose to obesity and insulin resistance, but the BB genotype is connected with an unfavorable lipid profile.

Serum adiponectin concentration and cardiovascular risk factors in climacteric women

Objective Adiponectin plays a significant role in the modulation of glucose tolerance and insulin sensitivity. We attempted to evaluate the relationship between adiponectin level and parameters of the menopausal metabolic syndrome: body mass index, waist-to-hip ratio, lipid profile and insulin resistance indices. Subjects and methods Thirty-two women and ten men aged 40–63 years were included. The percentage of body fat and of abdominal fat deposits were measured with dual-energy X-ray absorptiometry. Serum adiponectin, tumour necrosis factor-α (TNFα) and leptin were measured with commercially available radioimmunoassay kits. To exclude the influence of nutritional factors on adiponectin secretion, diet content was analysed in the preceding three days. Results Postmenopausal non-obese women had a non-significantly lower level of adiponectin compared with premenopausal women of corresponding body mass. Serum adiponectin level was significantly lower in postmenopausal obese women than in non-obese women (p = 0.0023). Men with similar age and body mass to the women had the lowest level of adiponectin (p = 0.06). Three months of estrogen replacement therapy in women with surgical menopause did not significantly change the serum level of adiponectin. We found a negative correlation of adiponectin with leptin, insulin resistance index and total cholesterol, and a positive correlation with high-density lipoprotein cholesterol. Adiponectin level was negatively correlated with free testosterone, but we did not find such a relationship with estradiol. There was no correlation of adiponectin level with TNFα; however, serum TNFα correlated positively with leptin. The dietary analysis showed no differences between the diets of obese and non-obese women over the preceding three days. Moreover, mean diastolic and systolic blood pressures were noted to be significantly lower in premenopausal women than in postmenopausal non-obese women (p = 0.05). Conclusions Our results suggest that adiponectin could be a marker of risk for developing menopausal metabolic syndrome. Moreover, it is possible that sex steroids have an influence on adiponectin secretion.

Waist circumference and serum adiponectin levels in obese and non-obese postmenopausal women.

OBJECTIVES A proposed missing link between obesity and metabolic disturbances is adiponectin, an adipocyte-derived peptide. Adiponectin is a potent antidiabetic hormone and seems to have a beneficial influence on lipid profile as well. The need to explain the complex physiological roles of this hormone prompted the authors to study the relationship between adiponectin level and obesity - related abnormalities in a homogenous population of postmenopausal women. STUDY DESIGN The study involved 272 postmenopausal women aged 50-60 years. Invitations to participate in the study were sent to 4000 randomly chosen women from the Wroclaw city population fulfilling the age criterion. A telephone questionnaire was administered to the group of 1731 women who responded to the invitation and then subjects for the study were selected. Main outcome measures anthropometrical measurements of body fat tissue content and fat tissue distribution assessment were carried out in all the women. Moreover, serum concentrations of adiponectin, glucose, total cholesterol, HDL cholesterol, triglycerides and insulin were measured. RESULTS The most frequent (76%) phenotype among the investigated women was obesity (BMI >25) with abnormal (=80cm) waist circumference (OAW), Obesity with normal (<80cm) waist (ONW) and normal weight with abnormal waist (NOAW) were observed in only 5% and 14% of the women, respectively. Non-obese women with normal waist (NONW) were noted in only 5% of the subjects. Serum adiponectin levels in both groups of non-obese women (NOAW and NONW) were significantly higher (p<0.05) than in the women with obesity or overweight and abnormal waist circumference (OAW group). Adiponectin levels in the women with obesity or overweight and normal waist (ONW) were also higher than in the OAW group; however, this difference was not statistically significant (p=0.05). In all the women, serum adiponectin level correlated negatively with BMI (r=-0.34, p=0.0001), total fat (r=-0.28, p=0.0001), android fat deposit (r=-0.23, p=0.0001), waist circumference (r=-0.33, p=0.0001), glucose (r=-0.27, p=0.0001), triglycerides (r=-0.34, p=0.0001), and FIRI (r=-0.34, p=0.0001) and positively with the gynoid/android fat deposit ratio (r=0.28, p=0.0001) and HDL cholesterol (r=0.36, p=0.0001). CONCLUSIONS These results confirm that adiponectin could be a marker of the development of menopausal insulin resistance syndrome.

Effect of moderate-intensity exercise on oxidative stress indices in metabolically healthy obese and metabolically unhealthy obese phenotypes in postmenopausal women: a pilot study.

Objective:The aim of this work was to determine whether the level of oxidative stress induced by moderate-intensity exercise depends on obesity phenotypes: metabolically healthy but obese (MHO) and non-metabolically healthy obese (at-risk obesity; non-MHO). Methods:We performed the study on 161 postmenopausal women aged 50 to 60 years. A metabolically healthy nonobese (MH-NO) group (n = 73), an MHO group (n = 27), and a non-MHO group (n = 61) exercised on a cycloergometer for 30 minutes at 50% of their peak oxygen consumption and were evaluated for oxidative status by determination of thiobarbituric acid-reactive substances (TBARS) and serum antioxidant activity (AS). Results:No difference was found in AS between the MH-NO group and the MHO group. The AS of the non-MHO group was significantly lower than that of the MH-NO group (P < 0.05) and that of the MHO group (P = 0.011). The insulin resistance index homeostasis model assessment was the only biochemical parameter that correlated with AS. After exercise, a significant increase in the TBARS concentration in all tested groups of women was observed, but differences in the increment of TBARS level between groups were not found. Conclusions:Antioxidant status in obese postmenopausal women depends on obesity phenotypes and is higher for women with the MHO than those with the non-MHO phenotype. Independently of obesity phenotype, obese postmenopausal women exposed to moderate-intensity exercise seem to be at similar risk for oxidative stress compared with their nonobese counterparts. We suggest that homeostasis model assessment be taken into account when planning physical exercise for obese people.

beta3-Adrenergic receptor polymorphism and metabolic syndrome in postmenopausal women

Objectives. Some studies indicate that the Trp64Arg polymorphism in the gene encoding the β3-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the present study was to evaluate the frequency of ADRB3 polymorphism and its association with metabolic syndrome in postmenopausal women. Methods. We performed the study on 284 randomly chosen postmenopausal women, aged 50–60 years, who were then selected to the study. Measurements of anthropometric parameters and biochemical estimations such as lipid profile, glucose and insulin level in serum were carried out using commercial kits. ADRB3 genotyping was performed by polymerase chain reaction and mini-sequencing. Results. The frequency of the Trp64/Arg64 genotype in the investigated population was 13%, and of the Trp64/Trp64 genotype, 85%. The Arg64/Arg64 genotype was present in only 2% of women. Metabolic syndrome was recognized in 22% of women bearing Trp64/Arg64 genotype and in 14% of women bearing Trp64/Trp64 genotype, without a statistically significant difference between the two groups (p > 0.05 in the χ2 test). Women bearing the Trp64/Arg64 genotype had lower serum levels of high-density lipoprotein cholesterol (HDL-C) than Trp64/Trp64 genotype women (63.2 ± 13.0 vs. 71.4 ± 17.4 mg/dl). Both groups did not differ in any other investigated parameter. Conclusion. Trp64Arg polymorphism of the β3-adrenergic receptor gene is not related to metabolic syndrome in postmenopausal Polish women; however, it seems to be associated with decreased HDL-C levels.

Post-exercise oxidative stress and obesity in postmenopausal women: The role of beta3-adrenergic receptor polymorphism

Aim. Some studies indicate that the Trp64Arg polymorphism in the gene encoding the β3-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the present study was to evaluate the frequency of this polymorphism and its relationship with obesity and oxidative stress in postmenopausal women. Material and methods. We performed the study on 200 women, aged 50–60 years. Estimation of anthropometric parameters and total body fat, android and gynoid fat deposits was carried out using dual-energy X-ray absorptiometry. Oxidative stress was estimated by measurement of thiobarbituric acid-reactive substances (TBARS) in serum. Blood for analysis was collected before, directly after and 6 h after a 30-min physical test on a cycle ergometer. ADRB3 genotyping was performed by polymerase chain reaction. Results. The frequency of Trp64/Arg64 genotype in the investigated population was 12%, and of Trp64/Trp64 was 87%. The Arg64/Arg64 genotype was present in only 1% of women. Women bearing the Trp64/Arg64 genotype did not differ in any measured anthropometric parameters from women bearing the Trp64/Trp64 genotype. Moreover, genotype had no influence on oxidative stress parameters. Likewise, in both groups, mean plasma level of TBARS was increased significantly (p < 0.05) directly after the endurance test and remained elevated 6 h after the test. Conclusions. The Trp64Arg polymorphism of ADRB3 seems to not be related to obesity in postmenopausal women. Moreover, the Trp64Arg polymorphism has no influence on oxidative stress intensification after standardized physical effort in postmenopausal women.

Endocannabinoid type 1 receptor gene (CNR1) polymorphisms (rs806381, rs10485170, rs6454674, rs2023239) and cardiovascular risk factors in postmenopausal women

Introduction. The risk of cardiovascular diseases (CVD) in women increases with menopausal stage. Obesity with metabolic disorders is the most important risk factor for CVD. The incidence of this phenotype of obesity increases in postmenopausal women. The endocannabinoid system plays an important role in regulation of several metabolic pathways. The aim of this work was to investigate whether genetic variations in the cannabinoid receptor gene (CNR1) can affect cardiovascular risk factors (e.g. fat distribution, obesity, fasting glucose, lipid profile, blood pressure, and free androgen and estrogen indexes) in postmenopausal women. Methods. The rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms of the CNR1 gene were genotyped in 384 randomly selected postmenopausal Polish women (aged 50–60) using the minisequencing technique. Results. The rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms were not significantly associated with anthropometric measures (waist circumference, carbohydrate and lipid metabolism, body mass index [BMI], total fat, glucose, insulin, fasting insulin resistance index [FIRI]). However, the rs2023239 polymorphism was associated with the free androgen index (p = 0.03). Discussion. It seems that further genotyping of the endocannabinoid receptor gene cannot be used as a significant marker of predisposition to CVD in postmenopausal women, but it would be interesting to study this interrelation on a larger population of postmenopausal women.

Cardiovascular disease risk factors associated with low level of physical activity in postmenopausal Polish women

Abstract Objectives: To determine whether physical activity level could have an effect on cardiovascular disease (CVD) risk factors in Polish postmenopausal women. Methods: We studied the associations of physical activity (PA) level with obesity indices, unfavorable lipid profile parameters and the insulin resistance index HOMA in 343 postmenopausal Polish women selected from an urban population, aged 50–60. Results: In the tested sample, a low level of PA significantly increased odds ratios for CVD risk factors such as BMI ≥ 30 kg/m2, total body fat (TBF) > 75th percentile, gynoid fat deposit (GFD) > 75th percentile, total cholesterol (TC) ≥ 5 mM, low-density lipoprotein cholesterol (LDL-C) > 3 mM and HOMA ≥ 1.95. Conclusions: Obesity and some metabolic CVD risk factors in postmenopausal women are directly associated with low PA level. Postmenopausal urban women should be persuaded to be physically active, as even moderate activity level seems to be sufficient to reduce the CVD risk in this group of individuals.

Are endocannabinoid type 1 receptor gene (CNR1) polymorphisms associated with obesity and metabolic syndrome in postmenopausal Polish women

Objective: The aim of this study was to determine whether genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity, fat distribution and obesity-related metabolic disorders in Polish postmenopausal women.Design and Subjects: The A3813G, G1422A and A4895G single nucleotide polymorphisms of CNR1 were genotyped in 348 randomly selected postmenopausal women aged 50-60 years recruited from the Wroclaw city population. Measurements: CNR1 genotypes, anthropometric measures (BMI, WC, body fat distribution by DEXA) and metabolic parameters (glucose, lipid profile, insulin FIRI) were determined.Results: The 3813G allele was not significantly associated with higher body mass, BMI, WC, total fat, or fat percentage, but was associated with higher android fat deposit (2971.78 &177; 1655.08 &177; 2472.64 &177; 1300.53, p = 0.007) and percentage of android fat (37.59 &177; 8.45 vs. 35.66 &177; 7.63, p = 0.062). The 1422A allele was associated with higher total fat (31587.72 &177; 9161.28 g vs. 26078.26 &177; 7552.14 g, p = 0.019), fat percentage (40.51 &177; 5.66% vs. 37.51 &177; 4.99%, p = 0.052), and percentage of android fat (40.86 &177; 9.73% vs. 36.09 &177; 7.70%, p = 0.047). No associations were observed for the A4895G variant.Conclusions: There is an association of variants of CNR1 with obesity-related phenotypes in Polish postmenopausal women. As CB1 is a drug target for obesity, pharmacogenetic receptor gene analysis of obesity treatment by endocannabinoid blockade may be of interest to identify the best responders.