Unraveling the Interplay between Nonalcoholic Fatty Liver Disease and Polycystic Ovary Syndrome in Adolescents: Pathogenesis, Prevalence, and Management Strategies.

BACKGROUND With the expanding understanding of conditions contributing to heightened cardiovascular risk, emerging pathologies like nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are being recognized as hepatic and ovarian manifestations of metabolic syndrome, respectively. This study aims to elucidate the recent advancements in our comprehension of the link between these conditions in the pediatric demographic, focusing on pathogenesis, incidence, diagnostic methods, and effective therapeutic strategies. MATERIAL AND METHODS A systematic review was conducted following the PRISMA 2020 guidelines, with a search of the PubMed database for eligible studies published in the ten years leading up to January 2023. RESULTS Out of 23 reports based on 16 original studies, we found a significantly higher prevalence of NAFLD in adolescents with PCOS compared to healthy controls. Factors such as increased de novo lipogenesis, alterations in gut microbiota, and a deficiency in growth differentiation factor-15 have been implicated in their pathogenesis. Additionally, novel biomarker S100A4, a clinical prediction score for hepatic steatosis in PCOS, and pharmacotherapy involving low-dose spironolactone, pioglitazone, and metformin have been proposed to enhance the management of these conditions. CONCLUSIONS A meticulous approach to the prevention, detection, and treatment of NAFLD in adolescents with PCOS is paramount to mitigate further complications. The study underlines the need for ongoing research to refine our understanding and management of these interconnected metabolic disorders.

The relationships between FLAIS, a novel insulin sensitivity index, and cardiovascular risk factors in a population-based study.

BACKGROUND: Insulin resistance is a risk factor for cardiovascular disease. Recently, we have developed a novel index, FLAIS (Fasting Laboratory Assessment of Insulin Sensitivity), which accurately reflects insulin sensitivity, measured with hyperinsulinemic-euglycemic clamp, in different groups of subjects. The aim of the present study was to assess the relationship of FLAIS with cardiovascular risk factors in a population-based study. METHODS: The study group comprised 339 individuals from the ongoing Bialystok Plus study, without previously known diabetes. Clinical examination, oral glucose tolerance test and the measurement of blood laboratory parameters were performed. RESULTS: Prediabetes (impaired fasting glucose and/or impaired glucose tolerance) was diagnosed in 165 individuals whereas type 2 diabetes was diagnosed in 19 subjects. FLAIS was lower in individuals with prediabetes and diabetes in comparison with individuals with normal glucose tolerance. FLAIS was significantly related to waist circumference, systolic and diastolic blood pressure, triglycerides, HDL-cholesterol and LDL-cholesterol in the entire study group and in the subgroups with normal glucose tolerance and with prediabetes/diabetes. HOMA-IR, QUICKI and Matsuda index were not related to blood pressure and LDL-cholesterol in individuals with normal glucose tolerance. Majority of the adjusted models with FLAIS were characterized by better fit with the data in comparison with other indices for all cardiovascular risk factors except waist circumference. CONCLUSIONS: FLAIS represents useful index to assess the cluster of insulin resistance-associated cardiovascular risk factors in general population.

Metabolic syndrome and its components in different phenotypes of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-age women. Important factors in its pathogenesis are hyperinsulinaemia and insulin resistance, which lead to higher risk of metabolic syndrome (MetS) and its complications. With the implementation of the Rotterdam diagnostic criteria in 2003, the group of PCOS patients became highly heterogeneous, with varying metabolic risk reported for different phenotypes of the syndrome. The aim of the present review is to assess the prevalence and severity of MetS and its components in patients with the four phenotypes of PCOS. A comprehensive search of Pubmed database was performed to identify studies comparing metabolic characteristics between PCOS patients with different phenotypes of the syndrome. The results of 60 studies published between 2004 and 2020 were retrieved and analysed. More adverse metabolic profile was observed in PCOS patients with hyperandrogenic phenotypes in comparison to normoandrogenic patients, as well as in classic phenotypes, defined by National Institutes of Health criteria, in comparison to newer phenotypes introduced by the Rotterdam criteria. In the majority of observations, normoandrogenic PCOS patients did not differ significantly from controls in terms of metabolic characteristics, although some East Asian studies reported more adverse metabolic profile in normoandrogenic phenotype in comparison to healthy women. In conclusion, metabolic abnormalities in PCOS seem to be associated with joint effects of hyperandrogenism, insulin resistance and visceral obesity. The differences observed between the four phenotypes of PCOS underline the need for individualised diagnostic and therapeutic approach.

Correction: Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

[This corrects the article DOI: 10.1371/journal.pgen.1007813.].

Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria.

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.

The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies.

The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells' differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies-type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.

Polycystic ovary syndrome and the risk of cardiometabolic complications in longitudinal studies.

The purpose of this study was to perform a review of the longitudinal studies to determine whether polycystic ovary syndrome is associated with higher prevalence of metabolic complications and cardiovascular morbidity and mortality. The primary outcomes included body mass index, metabolic syndrome and its components (waist circumference, lipid profile, arterial hypertension, abnormal glucose metabolism (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes), insulin resistance, and cardiovascular diseases like stroke, angina, and coronary heart disease. Complications in pregnant women were beyond the scope of this review. PubMed database (1992-2018) was searched to identify proper publications. Finally, data from 47 articles were analysed. Studies differed in the design (prospective, retrospective, cohort, observational), research methods, polycystic ovary syndrome diagnostic criteria, studied populations, race, and ethnicity of the participants. Based on the data collected, it appears that women with polycystic ovary syndrome have higher prevalence of obesity, abdominal fat distribution, dyslipidaemia and deterioration of glucose metabolism, but increased prevalence of cardiovascular diseases is not proven.

Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome.

Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δ irisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δ irisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δ irisin (ß=0.70, p=0.0002), FFAs 60' during the clamp study (ß=-0.22, p=0.01), SHBG (ß=0.54, p<0.0001) and the interaction between Δ irisin and PCOS (ß=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.

Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis.

The kynurenine pathway (KP) of tryptophan degradation includes several compounds that reveal immunomodulatory properties. The present study aimed to investigate the alteration in KP metabolites in young women with autoimmune thyroiditis (AIT) and their associations with thyroid function. The thyroid function tests, antithyroid antibodies measurement and ultrasonography of the thyroid gland have been performed in 57 young women with AIT and 38 age-matched healthy controls. The serum levels of tryptophan, kynurenine (KYN) and its metabolites were determined, and the activity of KP enzymes was calculated indirectly as product-to-substrate ratios. KP was activated and dysregulated in AIT, along with significantly elevated levels of KYN and anthranilic acid (AA), at the expense of the reduction of kynurenic acid (KYNA), which was reflected by the increase in the AA/KYNA ratio (p < 0.001). In univariate and multiple regression analyses, peripheral deiodinase (SPINA-GD) activity in AIT was positively associated with KYNA, AA, and quinolinic acid (QA). The merger of AA, AA/KYNA ratio, QA and SPINA-GD exhibited the highest sensitivity and specificity to predict AIT (p < 0.001) in receiver operating characteristic (ROC) analysis. In conclusion, the serum KYN metabolite profile is dysregulated in young women with AIT and could serve as a new predictor of AIT risk.

Cushing's disease presenting with recurrent abscesses followed by post-remission hyperthyroidism.

Summary: We report a case of a 59-year-old woman with Cushing's disease who developed hyperthyroidism following treatment of hypercortisolaemia. The patient with a history of recurrent hospitalisations caused by multi-sited soft tissue abscesses was admitted with sepsis. Both her medical history and physical examination suggested Cushing's syndrome. The initial hormonal diagnostic process, conducted after sepsis treatment, brought forth conflicting results. However, hormonal assessment repeated 3 months later indicated pituitary hypercortisolaemia, which was confirmed through bilateral inferior petrosal sinus sampling and was successfully treated with transsphenoidal pituitary surgery. Three months after the surgery, the patient was readmitted to our epartment with symptoms of hyperthyroidism, which was confirmed by laboratory tests. Thyroid scintiscans indicated Graves' disease. However, the absence of anti-thyroid stimulating hormone antibodies suggested other etiologies of hyperthyroidism. Eventually, the patient underwent radioiodine therapy. Currently, her condition is improving and she has had no recurrence of abscesses, severe infections, or hyperthyroidism. In conclusion, while clinical manifestation of hypercortisolaemia might be non-specific, its treatment may trigger the development of autoimmune diseases. Learning points: The presence of recurrent severe infections should prompt physicians to consider the possibility of hypercortisolaemia. Chronic hypercortisolism is debilitating and can lead to significant disability. Dexamethasone suppression testing in patients with active or recent severe inflammatory or infectious illnesses may produce misleading or confusing results. Clinicians should be aware of the potential development of autoimmune diseases following successful treatment of hypercortisolaemia.

Serum expression levels of selected microRNAs and their association with glucose metabolism in young women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances, such as insulin resistance and prediabetes, and the risk for their occurrence is especially increased in hyperandrogenic (HA) phenotypes of PCOS. Circulating microRNAs (miRNAs) may be involved in PCOS pathogenesis and regulation of metabolic processes. OBJECTIVES: The aim of the study was to assess expression levels of selected circulating miRNAs in women with PCOS and to investigate the relationship of these miRNAs with glucose metabolism. PATIENTS AND METHODS: The study included 95 patients with HA­PCOS and 76 healthy women similar to the study group in age and body mass index. Measurements of sex hormone concentrations, oral glucose tolerance test (OGTT), and transvaginal ultrasonography were performed. Serum levels of selected miRNAs (miR­27a, miR­34a, miR­106b, miR­193b, miR­181a, miR­181b, and miR­320) were assessed with real­time polymerase chain reaction, and their association with PCOS and glucose metabolism parameters was studied. RESULTS: Serum levels of all studied miRNAs, except for miR­34a, differed between the patients with HA­PCOS and healthy women (all P <0.05). In HA­PCOS, miR­27a and miR­320 levels correlated with fasting glucose (R = 0.33; P = 0.001 and R = -0.35; P <0.001, respectively) and insulin concentrations (R = 0.26; P = 0.01 and R = -0.23; P = 0.03, respectively). Additionally, the level of miR­27a correlated with mean glucose concentration during OGTT (R = 0.26; P = 0.01). No such correlations were observed in the healthy women. In linear regression analyses, both miR­27a and miR­320 were associated with fasting glucose concentrations after adjustment for potentially confounding factors in the HA­PCOS group only. CONCLUSIONS: The expression profile of circulating miRNAs is altered in patients with HA­PCOS. Circulating miR­27a and miR­320 could serve as potential biomarkers of glucose metabolism disturbances in PCOS.

The relationship between brain structure volumes, depressive symptoms and body composition in obese/overweight and normal-/underweight women.

Depressive symptoms are highly prevalent and heterogeneous in women. Different brain structures might be associated with depressive symptoms and body composition in women with obesity/overweight and normal-/underweight, although the data is limited. The analysis included 265 women from Bialystok PLUS population study, untreated with antidepressive or antipsychotic medications. The subjects underwent brain magnetic resonance imaging and body composition analysis. Beck Depression Inventory (BDI) score was inversely associated with nucleus accumbens volume (ß = -0.217, p = 0.008) in women with BMI ≥ 25 kg/m2, but with insula volume (ß = -0.147, p = 0.027) in women with BMI < 25 kg/m2 after adjustment for age and estimated intracranial volume (eTIV). In women with BMI ≥ 25 kg/m2, nucleus accumbens volume was inversely associated with the percentage of visceral fat and BDI score (ß = -0.236, p = 0.012, ß = -0.192, p = 0.017) after adjustment for age and eTIV. In women with BMI < 25 kg/m2, insula volume was positively associated with total fat-free mass and negatively with the BDI score (ß = 0.142, p = 0.030, ß = -0.137, p = 0.037) after adjustment for age and eTIV. Depressive symptoms might be associated with nucleus accumbens volume in overweight/obese women, while in normal-/ underweight women-with alterations in insula volume.

The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.

Circulating interleukin 6 and soluble forms of its receptors in relation to resting energy expenditure in women with anorexia nervosa.

CONTEXT: Anorexia nervosa (AN) is an eating disorder, resulting in sustained low weight and marked decrease in fat mass. Interleukin 6 (IL-6) may play a role in appetite, energy expenditure and body weight control. IL-6 acts through binding with membrane receptor (IL-6R) and activates glycoprotein 130 (gp130) signalling. Both IL-6R and gp130 are present in the blood in the soluble forms (sIL-6R and sgp130 respectively). sIL-6R sensitizes cells towards IL-6, whereas sgp130 inhibits gp130 signalling. OBJECTIVE: To estimate circulating IL-6/sIL-6R/sgp130 system and its relationships with body weight and resting energy expenditure (REE) in AN women. PATIENTS: We examined 19 women with AN and 27 healthy normal-weight female controls. MEASUREMENTS: Indirect calorimetry and the measurement of serum IL-6, sIL-6R and sgp130 concentrations were performed in all the subjects. RESULTS: REE was decreased in AN women (P < 0·001). Serum IL-6 was higher in AN women in comparison with control group (P = 0·005). Serum sIL-6R was lower (P = 0·009) and serum sgp130 was higher (P = 0·004) in AN women in comparison with controls. IL-6 and sIL-6R were related to REE in the entire study population (r = -0·54, P < 0·001 and r = 0·48, P = 0·001 respectively) and in AN group (r = -0·54, P = 0·024 and r = 0·60, P = 0·011 respectively). CONCLUSIONS: Increased IL-6 in AN seems to be compensated by the changes in sIL-6R and sgp130, which are directed towards inhibition of IL-6 action. The balance between these factors might play a role in the regulation of energy expenditure in AN.

Normal metabolic flexibility despite insulin resistance women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance (IR) is connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called "metabolic inflexibility". The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI<25 kg/m²) and 52 overweight or obesity (BMI>25 kg/m²), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (P<0.001) and obesity (P=0.005) were independently characterized by lower insulin sensitivity. PCOS (P=0.002) and obesity (P=0.001) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (P<0.001) in insulin-stimulated conditions in comparison to lean subject whereas PCOS had no effect on these parameters (P=0.29 and P=0.43; respectively). Metabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.

The influence of insulin infusion on the metabolism of amyloid ß peptides in plasma.

BACKGROUND: Accumulating body of evidence suggests pathophysiologic links between Alzheimer's disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid ß (Aß) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady-state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity. OBJECTIVE: The aim of this study was to analyze the influence of insulin on the plasma concentrations of Aß peptides. METHODS: Blood samples were collected from 20 healthy young male volunteers before insulin infusion (clamp) and then at 120 and 360 minutes. In the second protocol, insulin was accompanied by Intralipid, which is mainly a mixture of triacylglycerols, and heparin, given as an activator of lipoprotein lipase, inducing insulin resistance. Analyses of plasma Aß1-42, Aßx-42, Aß1-40, and Aßx-40 were performed with multiplexing technology. Furthermore, concentrations of the Aß peptides in healthy persons were compared with those in 16 type 1 DM patients receiving chronic insulin therapy. RESULTS: When applied alone (i.e., without Intralipid), insulin infusion increased concentrations of Aß42 (full length and N-terminally shortened) but not of Aß40. When combined with Intralipid, infusion of insulin resulted in increased concentrations of all peptides (nonsignificant tendency in case of Aßx-40). We did not observe differences between Aß peptide concentrations in healthy subjects and those in type 1 DM patients. CONCLUSION: Infusion of insulin in nonphysiologic high doses increases plasma concentrations of Aß peptides; in case of Aß40, only when applied together with Intralipid, which perhaps might be explained by hypothetical shift of insulin degrading enzyme activity from degradation of Aß peptides to the degradation of insulin.

The association between plasma N-terminal pro-brain natriuretic peptide concentration and metabolic disturbances in women with depressive symptoms.

BACKGROUND: The relationship between brain natriuretic peptides and depression was studied in patients with cardiovascular diseases (CVD), but the data in people without CVD are limited. Metabolic disturbances can be associated with natriuretic peptides' levels. The study aimed to assess serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in women with depressive symptoms and its relationship with metabolic disturbances. METHODS: The analysis included 347 women (20-60 years old) from Bialystok PLUS cohort study: 98 with depressive symptoms and 249 controls. Clinical examination, oral glucose tolerance test (OGTT) and assessment of lipid, sex hormone binding globulin (SHBG) and NT-proBNP concentrations in the blood were performed. The participants completed Beck Depression Inventory questionnaire. RESULTS: Metabolic syndrome was more frequent in the group of women with depressive symptoms compared to women without depressive symptoms. Women with depressive symptoms had lower NT-proBNP level than the control group - 45.88 (27.80-67.04) vs 56.49 (32.42-94.25) pg/mL, p = 0.027. Multiple linear regression analysis of all women showed that NT-proBNP level was reversely associated with the presence of depressive symptoms, waist circumference and heart rate and positively connected with age. In the group of women with depressive symptoms, we observed negative correlations between NT-proBNP level and insulin concentration at 60 min of OGTT, diastolic blood pressure and a positive correlation with SHBG. CONCLUSIONS: NT-proBNP level is decreased in women with depressive symptoms, which might be connected with metabolic disturbances in this group.

The prevalence of diabetes and prediabetes: a population-based study.

INTRODUCTION: Diabetes remains one of the top public health care priorities. Over 6% of the world's population is affected by type 2 diabetes; however, a similar number of individuals may be unaware of this diagnosis. OBJECTIVES: Our population­basedstudy aimed to investigate the true prevalence of diabetes and prediabetes in the general population of a medium­sized city in Poland. PATIENTS AND METHODS: The analysis included 1051 participants of the Bialystok PLUS population­based cohort study. In those who did not report a history of diabetes, the oral glucose tolerance test (OGTT) was performed. Medical history data were gathered using standardized questionnaires, and anthropometric as well as body composition measurements were performed. RESULTS: According to the medical history data, a total of 75 participants had diabetes (7.14%). Prediabetes (impaired fasting glycemia [IFG] or impaired glucose tolerance [IGT]) was identified in 410 individuals, including 241 participants with IFG (22.9%) and 169 patients with IGT (16.1%). Moreover, there were 71 individuals (6.75%) who were newly diagnosed with diabetes based on OGTT results. Overall, 146 patients with diabetes (13.8%) were identified. The ratio of lean mass to fat mass differed significantly between the patients with newly diagnosed diabetes and those without impaired glucose metabolism. CONCLUSIONS: Our cohort study demonstrated a high prevalence of undiagnosed diabetes in the Bialystok population. In addition, we showed that a large group of patients still remains undiagnosed for other hyperglycemic disorders. Abdominal obesity as well as imbalance between the fat and lean mass may predispose to diabetes.

Multimorbidity Patterns in the Urban Population in Poland.

A number of studies have been conducted on multimorbidity; however, there are different patterns in various countries, ethnicities and social groups. The aim of this study is to estimate the prevalence of multimorbidity (physical diseases) in the urban population in Poland. In this population-based study, we examined multimorbidity stratified by sex, age, educational attainment and professional activity. Sixty-seven conditions were identified based on self-reported history (known conditions) and completed examinations (unknown conditions). Among the overall individuals aged 20-80 years, 1422 (88.2%) of the total 1612 individuals, 787 (88.9%) of 885 women and 635 (87.3%) of 727 men were diagnosed with at least two chronic conditions. On average, 5.25 ± 3.5 conditions occurred in the study population. The number of diagnosed conditions per individual increased with age and decreased with higher educational levels, with differing pathways in women and men. Women showed a higher number of conditions than men in the same age groups and educational levels. Only among students, the level of multimorbidity was lower in women than in men. In the other occupational activity categories, it was already higher in women. The level of multimorbidity in employed and unemployed individuals in a particular sex cluster was similar. We identified a high prevalence of multimorbidity in the urban population in Poland varying by age, sex, education attainment and professional activity. Our work may help in the selection of appropriate screening tests based on age, sex and educational attainment in order to recognise multimorbidity based on both known and unknown conditions. Ultimately, it may impact clinical practice, service delivery and study design.

Role and mechanism of miR-335-5p in the pathogenesis and treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of unknown etiology that occurs in women of reproductive age. Despite being considered to affect up to one-fifth of women in this cohort, the condition lacks generally accepted diagnostic biomarkers and options for targeted therapy. Hereby, we analyzed the diagnostic, therapeutic, and functional potential of a recently discovered miR-335-5p that was observed to be reduced in the follicular fluid (FF) of PCOS patients as compared with healthy women. We found miR-335-5p to be significantly decreased in the serum and FF samples of PCOS patients (n = 40) vs healthy women (n = 30), as well as in primary human granulosa cells (hGCs), and in 3 different hormonally induced PCOS-like murine models vs. wild-type (WT) mice. The level of circulating miR-335-5p was found to significantly correlate with the impaired endocrine and clinical features associated with PCOS in human patients. Ovarian intrabursal injection of the miR-335-5p antagomir in WT mice ovaries induced a PCOS-like reproductive phenotype. Treatment with the miR-335-5p agomir rescued the dihydrotestosterone-induced PCOS-phenotype in mice, thereby providing a functional link between miR-335-5p and PCOS. We identified SP1 as a miR-335-5p target gene by using the dual-luciferase reporter assay. Both the luciferase reporter assay and chromatin immunoprecipitation assay showed that SP1 bound to the promoter region of human CYP19A1 and inhibited its transcription. miR-335-5p increased the production of estradiol via the SP1/CYP19A1 axis in hGCs, thereby suggesting its mechanistic pathway of action. In conclusion, these results provide evidence that miR-335-5p may function as a mediator in the etiopathogenesis of PCOS, as well as has the potential as both a novel diagnostic biomarker and therapeutic target for PCOS.