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.
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.
While obesity has been correlated with welfare in the general population, there is not much data on the influence of body composition on welfare among the non-obese adult individuals. In this study, ...a total of 726 non-obese individuals from the general population were analyzed. The mean age was 46.8 ± 15.4 years and 42.1% of participants were male. The anthropometric measurements and dual energy X-ray absorptiometry (DEXA) were done. The mean value for the Satisfaction with Life Scale (SWLS) was 23.09 ± 5.43, for Euro Quality of Life Visual Analogue Scale (EQ-VAS) was 78.0 ± 14.5, and for the Beck Depression Inventory (BDI) was 6.7 ± 6.6. On the SWLS, the higher waist-hip ratio had a negative impact even after adjusting for age, gender, and concomitant diseases. EQ-VAS was inversely associated with android fat distribution and directly associated with muscle mass. BDI value was inversely associated with lower muscle mass, especially in lower limbs. The well-being of women was mainly associated with the distribution of adipose tissue and less with the distribution of muscle tissue-abdominal fat distribution has a particularly negative impact on well-being among women. In contrast, men's well-being depends more on muscle mass and to a lesser extent on the distribution of fat tissue-a positive significant effect has lean mass and a circumference of thigh below gluteal fold.
In Poland there are still nearly 20 million individuals with hypercholesterolaemia, most of them are unaware of their condition; that is also why only ca. 5% of patients with familial ...hypercholesterolaemia have been diagnosed; that is why other rare cholesterol metabolism disorders are so rarely diagnosed in Poland. Let us hope that these guidelines, being an effect of work of experts representing 6 main scientific societies, as well as the network of PoLA lipid centers being a part of the EAS lipid centers, certification of lipidologists by PoLA, or the growing number of centers for rare diseases, with a network planned by the Ministry of Health, improvements in coordinated care for patients after myocardial infarction (KOS-Zawał), reimbursement of innovative agents, as well as introduction in Poland of an effective primary prevention program, will make improvement in relation to these unmet needs in diagnostics and treatment of lipid disorders possible.
Purpose
Insulin resistance is an important factor in the pathogenesis of polycystic ovary syndrome (PCOS), which is associated with higher risk of metabolic syndrome (MetS) and cardiovascular ...complications. Early atherosclerotic lesions may be diagnosed by ultrasonographic parameters: brachial artery flow-mediated dilation after reactive hyperaemia (FMD) and intima-media thickness of common carotid artery (IMT). The aim of the study was to assess the relation of IMT and FMD with clinical and laboratory parameters reflecting metabolic status in young women with different PCOS phenotypes.
Methods
The study included 154 PCOS patients diagnosed with the Rotterdam criteria, divided into four phenotypes, and 113 healthy women. Laboratory analyses, transvaginal ultrasound, and IMT and FMD measurements were conducted. MetS was diagnosed with International Diabetes Federation/American Heart Association (IDF/AHA) consensus criteria.
Results
MetS was more prevalent in PCOS patients than healthy women (14.29 vs. 5.31%;
p
= 0.019), with highest prevalence in phenotypes I and II (
p
= 0.039). IMT and FMD did not differ between PCOS patients and the controls, nor between the PCOS phenotypes. PCOS patients with MetS presented lower FMD than other PCOS patients (
p
= 0.018). In women with PCOS, FMD correlated with glucose and insulin concentrations in the fasting state (
R
= −0.33,
p
= 0.002;
R
= −0.23,
p
= 0.026) and at 2 h of OGTT (
R
= −0.29,
p
= 0.006;
R
= −0.26,
p
= 0.014). In patients with phenotype I, correlations were found between IMT and BMI (
R
= 0.45,
p
= 0.006) and between FMD and fasting glucose concentrations (
R
= −0.46,
p
= 0.011).
Conclusions
Metabolic disturbances and the diagnosis of MetS in patients with PCOS, especially in hyperandrogenic phenotypes, might be associated with alterations in IMT and FMD.
Abstract 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/m 2 ) – 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 (β = − 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.
OBJECTIVE:--Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled ...trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS--Patients (type 2 diabetes, aged 30-75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose <7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose <6.7 mmol/l). RESULTS:--A total of 1,115 patients were randomly assigned (PRANDIAL n = 557; BASAL n = 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n = 174, 31.2%) and BASAL (n = 181, 32.4%) groups were similar (hazard ratio 0.98 95% CI 0.8-1.21). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 ± 0.1 vs. 7.8 ± 0.1%; P = 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P < 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P < 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P < 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P = 0.233) versus the PRANDIAL group. CONCLUSIONS:--Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.
Data concerning metabolic consequences in women with polycystic ovary syndrome (PCOS) are delivered mainly by cross-sectional studies. In this research, we re-examined 31 Caucasian PCOS women after a ...median period of 120.9 months to evaluate the changes in metabolic syndrome components. Clinical examination, oral glucose tolerance test with estimations of glucose and insulin, lipids, sex hormone-binding globulin (SHBG) and sex hormones assessments were performed on two occasions. Additionally, the euglycaemic hyperinsulinaemic clamp technique was used at the baseline to assess insulin sensitivity (M-clamp value). In the end, the median age of participants was 35. We observed an increase in glucose concentrations, a decrease in insulin concentrations and no changes in insulin resistance markers. Final mean glucose, mean insulin, Matsuda index and body mass index (BMI) were correlated with baseline M-clamp value and SHBG (p < 0.01). During the follow-up, no one in the sample developed diabetes. The annualised incidence rate for conversion from normoglycaemia to prediabetes totalled 4.5%. Baseline BMI, free androgen index, fasting glucose and M-clamp value were identified as prediabetes predictors in young PCOS women (respectively, OR = 1.17, OR = 1.42, OR = 1.2, OR = 0.73, p < 0.05). Prediabetes appeared in 76.47% of the women with a final BMI of ≥ 25 kg/m2 and in 7.14% of the normal-weight women (p = 0.0001). In conclusion, we report a high rate of adverse change in glucose metabolism in overweight and obese participants, a deterioration in β-cell function and strong correlations between metabolic parameters assessed in the third and the fourth decade in PCOS women, emphasising the role of early intervention to prevent cardiometabolic diseases.
Women with polycystic ovary syndrome (PCOS) are characterized by insulin resistance and higher prevalence of obesity. Serum ferritin is increased in obesity and is associated with insulin resistance. ...The aim of the present study was to evaluate the relationships between serum ferritin concentration with insulin resistance and body composition estimated by dual-energy X-ray absorptiometry (DXA) in PCOS women in comparison to the control group.
One hundred four women were enrolled to the study-65 women with PCOS and 39 women matched for age and BMI as a control group. Serum ferritin concentration and oral glucose tolerance test (OGTT) were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. DXA was performed to estimate fat, fat-free mass, and visceral adipose tissue (VAT).
Women with PCOS have higher serum concentration of ferritin (
= 0.002), insulin at baseline (
= 0.03), at 60 min of OGTT (
= 0.01), at 120 min of OGTT (
= 0.004), HOMA-IR (
= 0.03), and VAT (
= 0.0001) in comparison to the control group. We observed a relationship of serum ferritin with insulin concentration at baseline (
= 0.25,
= 0.04) and at 120 min of OGTT (
= 0.31,
= 0.01) and with HOMA-IR (
= 0.30,
= 0.01) in the PCOS group. We noticed an association between serum ferritin concentration and VAT (
= 0.42,
= 0.001), trunk fat mass (
= 0.25,
= 0.04), and android fat mass (
= 0.25,
= 0.04) in the PCOS group. Multiple regression analysis revealed that ferritin (
= 0.02, β = 0.17), insulin at baseline (
= 0.001, β = 0.30), glucose at the 120 min of OGTT (
= 0.007, β = 0.26), and triglycerides (
= 0.001, β = 0.33) were independent predictors of VAT amount in PCOS women.
Elevated serum ferritin concentration is connected with insulin resistance as well as with DXA-estimated VAT, android, and trunk fat mass in PCOS women, and could be a marker of metabolic dysfunction.
The knowledge of polycystic ovary syndrome (PCOS) natural history is limited. Our objective was to assess the effect of aging on clinical, hormonal and sonographic ovarian PCOS features and ...additionally to identify parameters that impact the course of PCOS. A secondary aim was to supply additional information on the reproductive outcome in women with previously diagnosed PCOS. A longitudinal cohort study with a median follow-up of 120.9 months was conducted, and 31 Caucasian women previously diagnosed with PCOS according to the Rotterdam criteria were re-examined at a median age of 35. Clinical examinations; transvaginal ultrasound scans; and lipid, E-selectin and sex hormone assessments were performed at the beginning and at the end of the follow-up. It was observed that menstrual cycles became regular and sonographic morphology of ovaries was normalized in 55% and 49% of the participants, respectively (all p < 0.05). At the final assessment, 55% of the women no longer met the criteria for PCOS (p < 0.05). The age, follicle-stimulating hormone (FSH) and E-selectin assessed at the baseline were the most important predictors of the PCOS persistence into later years (respectively, OR = 0.84, OR = 0.39, OR = 1.08, all p < 0.05). Ninety-five percent of the patients who had ever been trying to conceive became pregnant a minimum of once. The women with persistent PCOS had worse metabolic and reproductive parameters compared to the women with resolved PCOS. Positive correlations were found between the number of miscarriages and ovarian volume, LH, androstenedione, 17-hydroxyprogesterone and an increase in E-selectin during the follow-up (R = 0.46, R = 0.59, R = 0.54, R = 0.49, R = 0.47, all p < 0.05). In conclusion, progressing from the third to the fourth decade is connected with a reduction in PCOS features, which seems to have a great impact on fertility of women with a previous diagnosis of PCOS. FSH and E-selectin, as determined at the initial PCOS diagnosis, had an impact on the disappearance of the syndrome years after.
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