Role of Melatonin in the Onset of Metabolic Syndrome in Women.

Metabolic syndrome (MetS) is a constellation of several associated cardiometabolic risk factors that increase the risk of developing type 2 diabetes mellitus (T2DM), cardiovascular diseases, and mortality. The role of hormonal factors in the development of MetS is assumed. In women, an insulin-resistant state that is associated with polycystic ovarian syndrome and increased deposition of intra-abdominal adipose tissue promotes the development of MetS and increases cardiovascular risk. The neuroendocrine hormone melatonin is secreted mainly at night under the regulatory action of the suprachiasmatic nucleus in the hypothalamus. Melatonin secretion is influenced by exogenous factors such as light and seasons and endogenous factors such as age, sex, and body weight. At present, the role of melatonin in metabolic disorders in humans is not fully understood. In this review, we set out to analyze the relationship of melatonin with the main features of MetS in women. Data from experimental and clinical studies on the role of melatonin in glucose metabolism and on the involvement of melatonin in lipid disturbances in MetS are reviewed. The complex influence of melatonin on hypertension is discussed. The changes in melatonin, leptin, and ghrelin and their relation to various metabolic processes and vascular dysfunction are discussed.

SARS-CoV-2-induced adrenal crisis in a patient with autoimmune polyglandular syndrome type 1: case report.

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by the coexistence of endocrine and non-endocrine dysfunctions mediated by autoimmune mechanisms. Autoimmune polyglandular syndrome type 1 is defined as coexistence of chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Addison's disease as the obligatory component is potentially life threatening.Herein, we demonstrate a case of a 44-year-old woman with APS-1 (hypoparathyroidism, adrenal insufficiency, hypergonadotropic hypogonadism) and SARS-CoV-2-induced adrenal crisis. The patient presented with the typical manifestations of hypotensive shock, electrolyte disturbances of hyponatremia and hyperkalemia, and hypoglycaemia.Our case report illustrates the increased risk of severe course of COVID-19 in APS-1 syndrome patients along with heightened exposure to medical complications. The case reinforced the significance of a timely diagnosis, appropriate treatment, and education of patients with such a rare condition like APS-1.

Contribution of Components of Metabolic Syndrome to Cognitive Performance in Middle-Aged Adults.

INTRODUCTION: Metabolic syndrome (MetS) has been associated with impaired cognition in different cognitive domains. This study investigated the association between MetS and cognitive functioning in middle-aged Bulgarians across different definitions of MetS severity. MATERIAL AND METHODS: Our cross-sectional sample included 112 participants (67 free of MetS and 45 with MetS) with a mean age of 50.04 ± 3.31 years. The following MetS variables were considered-presence of MetS, continuously measured MetS components, dichotomized MetS components, number of MetS components present, and Metabolic Syndrome Severity Score (MSSS). Participants' cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). We employed multivariate regression models to investigate the associations between different measures of MetS severity and CERAD-NB total and subtest scores. RESULTS: Bivariate analyses showed that the CERAD-NB total score was significantly higher in women, participants with a university degree, those with normal blood pressure, normal waist circumference, and low triglyceride levels, compared with their counterparts. MetS participants had lower CERAD-NB total score (78.87 ± 6.89 vs. 84.97 ± 7.84) and specifically performed poorer on the subtest Word List Recall (7.16 ± 1.52 vs. 7.99 ± 1.52). These findings persisted after controlling for age, gender, and education. Next, generalized linear regression indicated that the CERAD-NB total score was lower in participants with MetS (ß = -4.86; 95% confidence interval [CI]: -7.60, -2.11), those with more MetS components (ß = -8.31; 95% CI: -14.13, -2.50 for fours vs. 0 components) and with an increase in MSSS (ß = -3.19; 95% CI: -4.67, -1.71). Hypertension independently contributed to lower CERAD-NB total score (ß = -4.00; 95% CI: -6.81, -1.19). CONCLUSIONS: Across several definitions, MetS was associated with lower cognitive functioning, and MetS severity appeared to be a better predictor than most MetS components. Recognizing and reducing severity of MetS components might be helpful in supporting cognitive functioning. Further longitudinal research is needed to shed more light on the relationship between MetS and cognitive functioning across the life span.

Cortisol Correlates with Structural Magnetic Resonance Imaging Parameters in Middle Aged Bulgarian Patients with Metabolic Syndrome: A Pilot Study.

BACKGROUND: There is a dose-dependent relationship between chronically increased cortisol levels and the number of metabolic syndrome (MetS) components. Both cortisol and MetS are linked to various brain abnormalities. AIM: To investigate an association of MetS components and salivary cortisol levels with cortical thickness in middle-aged Bulgarian patients with MetS. MATERIALS AND METHODS: We examined 26 healthy volunteers (mean age 50, 16±3.1 yrs) divided into two groups depending on whether or not they were diagnosed with MetS. Salivary cortisol was sampled and tested at two time points -morning and evening. Cortical thickness measures were obtained from structural T1-images using FreeSurfer software. We performed vertex-wise analysis across entire cortex and for preselected brain regions in frontal, temporal and cingulate cortex partial correlation analysis, accounting for gender. RESULTS: The control group consisted of 12 women; in the MetS group there were 6 men and 8 women. The whole brain analysis showed that waist circumference (WC) was negatively correlated with cortical thickness in rostro-lateral area in left frontal lobe and the right lateral orbito-frontal cortex. Morning cortisol levels, accounting for sex and WC, correlated negatively with thickness in left superior temporal area (r = -0.477, p = 0.039) and entorhinal area (r = -0.465, p = 0.045) and left mediotemporal cortex (r = -0.477, p = 0.038). CONCLUSION: Our pilot study confirmed that WC is associated with brain atrophic changes mainly in the frontal lobe. Our finding that cortisol levels negatively correlate with thinning of the cortex in temporal lobe should be further explored in subsequent study.

Metabolic syndrome severity score: range and associations with cardiovascular risk factors.

INTRODUCTION: Metabolic Syndrome Severity Score (MSSS) is a new clinical prediction rule (CPR) for diagnostic and therapeutic decisions and employs available components (sex, age, race, systolic blood pressure, waistline circumference, high-density lipoprotein, triglycerides and fasting blood glucose). The aim of our work was to perform cross-sectional pilot trial on middle-aged healthy volunteers and patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2DM) for studying feasibility and implementation of MSSS and its associations with cardiovascular risk factors. MATERIAL AND METHODS: We approached 64 eligible participants from Bulgaria. The MSSS values, together with demographic, anthropometric, medical history, laboratory findings, CVD risk factors, QRISK2 score for 10-year cardiovascular risk and predicted heart age, were analysed. Descriptive statistics with tests for comparison (e.g., t-test, χ2) between groups as well as ANOVA and logistic regression were applied. RESULTS: We analysed data from 56 participants (aged 50.11 ±3.43 years). The MSSS was higher in MetS patients (including 6 T2DM patients) than in controls (n = 29; 51.8%) presented as percentiles (69.97% and 34.41%, respectively) and z-scores (0.60 and -0.45, respectively) (p < 0.05). The logistic regression model of MSSS indicated a positive association with MetS/T2DM cases (correctness > 85%, p < 0.01). For further validation purposes, positive correlations of MSSS with CVD risk factor as diastolic blood pressure (Rho = 0.399; p < 0.003) and QRISK2 score (Rho = 0.524; p < 0.001) or predicted heart age (Rho = 0.368; p < 0.007) were also found. CONCLUSIONS: The pilot study of MSSS in Bulgaria indicated feasibility and consistency of its implementation among patients with metabolic syndrome and/or T2DM and healthy volunteers.

Role Of Vitamin D And Adipose Tissue Hormones In Women With Reproductive Disorders.

The role of vitamin D beyond that it plays in bone metabolism and calcium homeostasis has been lately quite emphasized. In this respect, vitamin D deficiency has been associated with higher risk of cardiovascular disease, metabolic syndrome, and reproductive disorders. Growing evidence has suggested that vitamin D deficiency is implicated in the pathogenesis of insulin resistance and the development of metabolic disorders in the polycystic ovary syndrome. The goal of the review is to present contemporary concepts of the relationship between hormones affecting the metabolic body status, serum vitamin D levels and the reproductive function.

Serum melatonin in women with polycystic ovary syndrome.

UNLABELLED: There has been a surge of interest in recent years in studying the changes of serum melatonin concentrations in disorders that are associated with insulin resistance such as diabetes mellitus type 2 and polycystic ovary syndrome (PCOS). AIM: The present study was designed to investigate the day-time and night-time levels of serum melatonin and the cortisol rhythm in women with PCOS and compare them with those of healthy women. PATIENTS AND METHODS: This is a case-control study which included 30 women with PCOS and 25 healthy women. All hormonal measurements in both the study group and controls were carried out between days 3 and 5 counted from the beginning of the last regular menstrual cycle; they included serum levels of melatonin and cortisol at 03:00 a.m and 08:00 a.m, total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), follicle stimulating hormone (FSH), and immunoreactive insulin at 08:00 a.m. RESULTS: Women with PCOS were found to have a significantly higher melatonin level at 08:00 a.m. and smaller mean night-day difference in the concentrations of melatonin in comparison with those of healthy women (natural log (Ln) night-day difference 0.60 +/- 0.10 pg/ml versus 1.15 +/- 0.14, p < 0.002). Melatonin to cortisol ratios at 03:00 a.m. and 08:00 a.m. showed no statistically significant differences between the two groups (Ln melatonin/cortisol 03:00 a.m., 1.01 +/- 0.06 versus 1.05 +/- 0.05; Ln melatonin/cortisol at 08:00 a.m., 0.62 +/- 0.01 versus 0.56 +/- 0.03, p > 0.05). CONCLUSION: The results we obtained about the changes of melatonin in women with PCOS could help in elucidating the complex pathophysiological pattern of this disease.

Effect of transdermal testosterone or alpha-lipoic acid on erectile dysfunction and quality of life in patients with type 2 diabetes mellitus.

UNLABELLED: Erectile dysfunction (ED) is the inability to develop and/or maintain an erection that is sufficient for satisfactory sexual intercourse. The prevalence of erectile dysfunction in diabetic men is 28-75%, this percentage rising with patient's age and duration of diabetes. The AIM of the present study was to investigate erectile dysfunction and quality of life in patients with type 2 diabetes mellitus (T2DM) after treating them with transdermal testosterone or with alpha-lipoic acid. MATERIALS AND METHODS: The effect of a 12-week treatment with transdermal testosterone or alpha-lipoic acid on the erectile function and quality of life of 45 men with ED and T2DM was studied in a randomized, prospective, open clinical, comparative study. The parameters we measured in the patients were body weight and body mass index (BMI); the albumin, lipids, HbA1C, testosterone (T), sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH) and microalbuminuria levels; the International Index of Erectile Function (IIEF) and Health related quality of life (SF-36) questionnaires were completed to evaluate ED and quality of life before and after 12 weeks of treatment with alpha-lipoic acid (600 mg, parenterally, for 7 days, followed by 600 mg received per os) or with transdermal testosterone in a dose of 50 mg daily. RESULTS: Testosterone treatment decreased BMI significantly (p < 0.01), increased testosterone concentrations (p < 0.01) and raised the SHBG levels (p < 0.05), improved the glycemic control and lipid profile (total cholesterol, p < 0.05; HDL cholesterol, p < 0.05; triglycerides, p < 0.05). The patients treated with alpha-lipoic acid had their BMI (p < 0.01), HbA1C (p < 0.01), total cholesterol (p < 0.01), HDL-cholesterol (p < 0.01) and triglycerides (p < 0.01) significantly reduced. The indicators for ED in both groups were also statistically significantly improved. There was improvement for all patients' self-assessment score for "physical functioning" (p = 0.001), for "role limitations due to physical health" (p < 0.001) and for "general health perception" (p = 0.021). CONCLUSIONS: Transdermal testosterone and alpha-lipoic acid have a tangible beneficial effect on erectile dysfunction and on metabolic disorders in T2DM patients and can be used to treat such patients.

Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

UNLABELLED: The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. MATERIALS AND METHODS: The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. RESULTS: Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. CONCLUSION: The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

Effect of short-term standard therapeutic regimens on neuropeptide Y and adipose tissue hormones in overweight insulin-resistant women with polycystic ovary syndrome.

AIM: The study was aimed at elucidating the influence of a 3-month treatment with routine therapeutic regimens--oral hormonal contraceptives (OHC) with antiandrogenic activity (a standard combination of ethynil estradiol 35 microg plus cyproterone acetate 2 mg) in combination with insulin sensitizing agents--metformin (Group I) and rosiglitazone (Group II) on adipose tissue hormones and hypothalamic neuropeptide Y (NPY) in women with polycystic ovary syndrome. PATIENTS AND METHODS: The study included 66 overweight insulin resistant women with PCOS according to the recent ESHRE-ASRM criteria randomized into 2 age-matched therapeutic groups. RESULTS: Significant decrease of leptin (P < 0.01; P = 0.001, resp.), resistin (P < 0.01; P < 0.01, resp.), tumour necrosis factor alpha (TNF alpha) (P = 0.001; P < 0.001, resp.), and NPY (P < 0.05; P < 0.001, resp.) was observed in both groups after treatment. These findings were in parallel with a significant decrease in the anthropometric parameters of body weight in the metformin group only. No significant changes in hormonal characteristics of the groups were found except for a significant decrease in androstenedione and DHEA-S (P < 0.05) in the metformin group and in 17-OH-progesterone (P < 0.05) in the rosiglitazone group. HDL-cholesterol rose and diastolic blood pressure fell significantly (P < 0.05) in the metformin group. CONCLUSION: Our data suggest beneficial effects of the treatment on potential cardiovascular risk in insulin resistant PCOS women.

Serum leptin levels correlate with clinical and biochemical indices of insulin resistance in women with polycystic ovary syndrome.

OBJECTIVES: To compare serum leptin levels in women with polycystic ovary syndrome (PCOS) and healthy subjects, and to evaluate the relationship between leptin concentration and insulin resistance. METHODS: Forty-five women with PCOS and 20 controls were included in the study. Serum levels of leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, LH and FSH were measured. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed. RESULTS: Serum leptin levels in PCOS patients were higher than in the control group independently of BMI, WHR and waist circumference. In PCOS patients there was a strong positive correlation between leptin and IRI (r = 0.592, p < 0.01) on the one hand, and leptin and HOMA-IR, on the other (r = 0.637, p < 0.01). In PCOS patients with more pronounced insulin resistance (IR) the correlation between leptin levels and HOMA-IR is independent of BMI, WHR and waist circumference. We did not find any correlation between leptin and other hormonal indices in PCOS patients. CONCLUSIONS: Our study confirms the existence of a significant positive correlation between serum leptin levels and clinical and hormonal indices of IR. The hyperleptinaemia is probably due to leptin resistance and may be characteristic of the syndrome. The lack of correlation with other hormonal parameters is probably due to the heterogeneity of the PCOS group.

Serum ghrelin level in women with polycystic ovary syndrome and its relationship with endocrine and metabolic parameters.

AIMS: To compare ghrelin levels in women with polycystic ovary syndrome (PCOS) and healthy subjects and to evaluate the relationships between circulating ghrelin and the heterogeneity of clinical and biochemical manifestations of PCOS women. METHODS: Forty-five women with PCOS and 20 controls were included in the study. Serum levels of ghrelin, leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, luteinizing hormone and follicle-stimulating hormone were measured. Free androgen index and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. RESULTS: Serum ghrelin levels in PCOS patients were lower than in the control group (mean+/-standard error of the mean: 21.78+/-2.12 vs. 34.67+/-3.57 ng/ml; p = 0.04). In women with PCOS, a strong negative correlation was observed between ghrelin values and the clinical (BMI, WHR, waist circumference) and hormonal indices of insulin resistance (IRI and HOMA-IR). The negative correlative relationship between ghrelin and HOMA-IR disappeared after partial correlation analysis when controlling for WHR and BMI. Negative correlation existed between ghrelin and testosterone (r = -0.315; p<0.05) and between ghrelin and leptin levels (r = -0.306; p<0.05). The latter correlation disappeared after partial correlation analysis controlling for BMI, WHR and HOMA-IR. CONCLUSION: The ghrelin level in women with PCOS reflects the metabolic and hormonal changes which are characteristics of the syndrome. The inverse correlation between ghrelin and leptin in these women is mediated through metabolic factors.