Diana Jędrzejuk

Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism

Many animal and human studies show that supraphysiological doses of dehydroepiandrosterone (DHEA) can influence body composition and carbohydrate and lipid metabolism. Most studies have concentrated on women and have not been randomized, thus creating controversial results. With this in mind, we designed a cross-over double-blind placebo-controlled study of 12 men aged 59.0 ± 4.8 years, who received either 50 mg/24 h DHEA or placebo for 3 months to assess the influence of DHEA on the content and distribution of fat tissue and serum insulin, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels, as well as testosterone, estradiol, DHEA-sulfate (S), prostate-specific antigen (PSA) concentrations and indexes of insulin sensitivity and resistance. Patients were recruited from university employees attending for periodic health checks, with normal hepatic and renal function with endogenous DHEA-S level < 1500 ng/dl. Our results did not reveal any significant changes in study parameters, apart from a statistically significant increase in DHEA-S levels after therapy with active substance.

Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis

Background Because of the great controversy over the role of androgens in the pathogenesis of atherosclerosis, we investigated the relationship between serum sex hormone levels and angiographically confirmed coronary artery disease in men. Material and methods We investigated 86 men aged 40–60 years, 56 with coronary artery disease and 30 healthy men, matched by age, as a control group. Body mass index and waist to hip ratio were calculated and total body fat mass and percentage of abdominal deposit were investigated by dual-energy X-ray absorptiometry (Dpx ( + ) Lunar, USA). The serum levels of sex hormones and insulin were measured using commercial radioimmunoassay and IRMA (by SHBG) kits (DPC, USA). The serum levels of lipids and glucose were assessed by means of enzymatic methods. Results Men with coronary artery disease had lower total testosterone levels (17.01 ± 6.42 vs. 19.37 ± 6.58 nmol/l; p < 0.05), testosterone/estradiol ratio (228.5 ± 88.5 vs. 289.8 ± 120.1; p < 0.05) and free androgen index (FAI) (59.49 ± 14.79 vs. 83.03 ± 25.81; p < 0.0001), and higher levels of estrone (49.5 ± 27.7 vs. 36.6 ± 12.7 pg/ml) than men in the control group. Moreover, men with coronary artery disease were more insulin-resistant than controls and had an atherogenic lipid profile. There was an inverse correlation (p < 0.05) between testosterone level and serum level of glucose (r = −0.29), triglycerides (r = −0.37), body mass index (r = −0.55), waist (r = −0.43), total body fat mass (r = −0.3) and fasting insulin resistance index. A significant positive association (p < 0.05) was found between testosterone and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol level in serum (r = 0.26). Conclusions Low levels of total testosterone, testosterone/estradiol ratio and free androgen index and higher levels of estrone in men with coronary artery disease appear together with many features of metabolic syndrome and may be involved in the pathogenesis of coronary atherosclerosis.

Left Ventricular Function Impairment in Patients With Normal-Weight Obesity Contribution of Abdominal Fat Deposition, Profibrotic State, Reduced Insulin Sensitivity, and Proinflammatory Activation

Background— Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. Methods and Results— One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m2 and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (&bgr;=−0.17, P<0.006), C-reactive protein (&bgr;=−0.20, P<0.002) and abdominal fat deposit (&bgr;=−0.20, P<0.003); for tissue S velocity, PICP (&bgr;=−0.21, P<0.002) and abdominal fat deposit (&bgr;=−0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (&bgr;=−0.30, P<0.0001), PICP (&bgr;=−0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; &bgr;=−0.20, P<0.002); and for E/e′-PICP, IL-18 (both &bgr;=0.18, P<0.01) and HOMA IR (&bgr;=0.16, P<0.04). Conclusions— In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

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.

Quantitative ultrasound of the heel and some parameters of bone turnover in patients with acromegaly.

Abstract: Acromegaly caused by growth hormone (GH) hypersecretion is characterized by enhanced skeletal growth and soft tissue enlargement. Insulin-like growth factor-1 (IGF-1) is the main peripheral mediator of GH action and it has a crucial role in the maintenance of a normal bone mass. However, in some patients with acromegaly, secondary osteoporosis is observed, despite the strong anabolic effect of GH and IGF-1 in bones. It is thought to be due to hypogonadism. The bone changes are accompanied by increased turnover. The aim of this study was to assess bone properties by ultrasound and turnover in patients with acromegaly. The study was carried out in 26 patients (13 men, 13 women): 14 with active acromegaly and 12 cured by surgery who had non-active disease. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and their combination Stiffness Index (SI) by quantitative ultrasound (QUS) of the heel, hormonal status, serum osteocalcin (OC) concentration and the urinary excretion of pyridinoline collagen crosslinks (PYR) were all studied. Controls were 20 age- and sex-matched healthy persons. We observed statistically significantly lower QUS values in patients with active disease than in those whose disease was cured. The differences were more pronounced in men. QUS values were lower in the entire group of patients compared with the controls; however, the differences were not statistically significant. Serum OC concentrations and urinary PYR excretion were higher in active disease. Statistically significant inverse correlations between serum GH levels and SOS (r=–0.58, p = 0.002); BUA (r=–0.66; p= 0.0001); T-score (r = −0,65, p= 0.0001) and Z-score (r=–0.66, p = 0.0001) were found only in male patients. No correlations between IGF-1, duration of the disease, OC, PYR and other data studied were observed. In conclusion, we have shown decreased QUS parameters suggesting impaired bone properties and quality in terms of density and elasticity in men, but not in women, with active acromegaly. This finding suggests osteoporosis with increased bone turnover. The above-mentioned changes might be caused by the action of GH on trabecular bone and its metabolism, since no hypogonadism in male patients was shown. Moreover, the influence of acromegaly on heel geometry and soft tissue swelling should also be considered.

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.

Consequences of menopause in women with diabetes mellitus - a clinical problem.

Human life was prolonged by 30 years in the past century, with the result that about 40% of a womans life falls within the postmenopausal period. The consequences, both early and remote, in the form of cardiovascular disease, osteoporosis and neoplastic disease are most pronounced in women suffering from one of the most common diseases, i.e., diabetes mellitus and the metabolic syndrome preceding it. These patients are problematic for physicians, and for this reason a study of diagnostic and therapeutic management was undertaken on the basis of our own experience as well as examination based on evidence-based medicine. Prior to making therapeutic decisions it is necessary to determine cardiovascular, thromboembolic and breast cancer risk factors. Hormonal therapy may be helpful in young postmenopausal women who are free of risk factors, and its composition and route of administration are significant considerations. Women with risk factors and who are more than 10 years after menopause should be administered alternative therapy depending on the diagnosed pathology.