Peripubertal Alterations of Leptin Levels in Patients with Autism Spectrum Disorder and Elevated or Normal Body Weight.

Leptin, which plays a key role in energy homeostasis, is known as a neurotrophic factor possibly linking nutrition and neurodevelopment. Available data on the association between leptin and autism spectrum disorder (ASD) are confusing. The aim of this study was to explore whether plasma levels of leptin in pre- and post-pubertal children with ASD and/or overweightness/obesity differ from those of BMI- and age-matched healthy controls. Leptin levels were determined in 287 pre-pubertal children (mean age 8.09 years), classified as follows: ASD with overweightness/obesity (ASD+/Ob+); ASD without overweightness/obesity (ASD+/Ob-); non-ASD with overweightness/obesity (ASD-/Ob+); non-ASD without overweightness/obesity (ASD-/Ob-). The assessment was repeated in 258 of the children post-pubertally (mean age 14.26 years). There were no significant differences in leptin levels either before or after puberty between ASD+/Ob+ and ASD-/Ob+ or between ASD+/Ob- and ASD-/Ob-, although there was a strong trend toward significance for higher pre-pubertal leptin levels in ASD+/Ob- than in ASD-/Ob-. Post-pubertal leptin levels were significantly lower than pre-pubertal levels in ASD+/Ob+, ASD-/Ob+, and ASD+/Ob- and higher in ASD-/Ob-. Leptin levels, elevated pre-pubertally in the children with overweightness/obesity as well as in children with ASD and normal BMI, decrease with age, in contrast to the increasing leptin levels in healthy controls.

Selected Essential and Toxic Chemical Elements in Hypothyroidism-A Literature Review (2001-2021).

Thyroid hormones are known for controlling metabolism of lipids, carbohydrates, proteins, minerals, and electrolytes and for regulating body temperature. Normal thyroid status depends on the chemical/elemental composition of body fluids and tissues, which changes depending on physiological state, lifestyle and environment. A deficiency or excess of certain essential chemical elements (selenium, zinc, copper, iron or fluorine) or exposure to toxic (cadmium or lead) or potentially toxic elements (manganese or chromium) interacts with thyroid hormone synthesis and may disturb thyroid homeostasis. In our review, accessible databases (Scopus, PubMed and Web of Science) were searched for articles from 2001-2021 on the influence of selected chemical elements on the development of hypothyroidism. Our review adopted some of the strengths of a systematic review. After non-eligible reports were rejected, 29 remaining articles were reviewed. The review found that disruption of the physiological levels of elements in the body adversely affects the functioning of cells and tissues, which can lead to the development of disease.

Autism spectrum disorder: Trace elements imbalances and the pathogenesis and severity of autistic symptoms.

The identification of biomarkers as diagnostic tools and predictors of response to treatment of neurological developmental disorders (NDD) such as schizophrenia (SZ), attention deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD), still remains an important challenge for clinical medicine. Metallomic profiles of ASD patients cover, besides essential elements such as cobalt, chromium, copper, iron, manganese, molybdenum, zinc, selenium, also toxic metals burden of: aluminum, arsenic, mercury, lead, beryllium, nickel, cadmium. Performed studies indicate that children with ASD present a reduced ability of eliminating toxic metals, which leads to these metals' accumulation and aggravation of autistic symptoms. Extensive metallomic studies allow a better understanding of the importance of trace elements as environmental factors in the pathogenesis of ASD. Even though a mineral imbalance is a fact in ASD, we are still expecting relevant tests and the elaboration of reference levels of trace elements as potential biomarkers useful in diagnosis, prevention, and treatment of ASD.

Lead Levels in Non-Occupationally Exposed Women with Preeclampsia.

There are many controversies regarding the relationship between lead exposure andcomplications in pregnancy. Preeclampsia (PE) is a maternal hypertensive disorder which is one of the main causes of maternal and foetal mortality. The aim of our study was to assess blood lead level (BLL) in Polish women with PE (PE group, n = 66) compared with healthy, non-pregnant women (CNP group, n = 40) and healthy pregnant women (CP group, n = 40). BLL was determined by inductively coupled plasma mass spectrometry (ICP-MS). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and BLL in the CP group were significantly lower than in the PE group (p < 0.001). Logistic regression analyses of BLL showed a significant positive relationship with the presence of PE. Furthermore, both the SBP and DBP values were positively associated with BLL. This study indicates that preeclamptic women tend to present with significantly higher BLL compared to healthy pregnant women. There were no differences in the BLL between the CP and CNP groups.

Alterations of urinary perchlorate levels in euthyroid postpubertal children with autism spectrum disorder.

BACKGROUND: Perchlorates ClO4(-) are known environmental and food contaminants that act as inhibitors of iodine uptake by the thyroid gland; however, information concerning their possible association with the development of autism spectrum disorder (ASD) is still missing. The current study is first presenting the alterations in perchlorate urine levels in euthyroid children with ASD. OBJECTIVES: To examine urinary perchlorates and iodides in euthyroid children diagnosed with ASD, compared to age-, and BMI-matched neurotypical controls, and to verify the association between these two ions in ASD. METHODS: Ions were determined in 24 h urine samples determined by ion chromatography-conductivity cell detection (IC-CD) and ion chromatography-pulsed amperometric detection (IC-PAD) techniques, respectively, in a total of 130 postpubertal euthyroid children with normal BMI (the mean age 14.46 years, SD = 1.32; the mean BMI 20.6, SD = 1.37), divided into age- and BMI-matched groups of ASD patients and neurotypical, healthy children (control). RESULTS: The ASD group presented with significantly higher perchlorate urine levels than the controls (median = 1.05 µg/L, interquartile range(IQR) = 1.5 versus median = 0.09 µg/L, IQR = 0.097, respectively), as well as lower iodide urine levels (median = 100.2 µg/L, IQR = 37 versus median = 156.95 µg/L, IQR = 26.11, respectively). The ASD group presented significantly lower TSH and higher free thyroid hormone (fT4, fT3) levels than the controls. In regression analyses, perchlorate urine levels showed significant positive relationships with normal BMI values and serum TSH, and inverse relationships with serum fT4. Urinary iodide levels showed significant inverse relationships with BMI values. The absence of ASD was associated with decreased odds of perchlorate urine levels (OR = 0.012, 95 % confidence interval [CI] 0.0002-0.76), and increased odds of iodide urine levels (OR = 1.15, 95 %CI 1.05-1.27). CONCLUSIONS: ASD may have an independent and significant impact on perchlorate as well as iodide levels in urine of euthyroid lean postpubertal children. Perchlorate levels do not appear to be directly associated with iodide levels in euthyroid children.

Are Obese Patients with Autism Spectrum Disorder More Likely to Be Selenium Deficient? Research Findings on Pre- and Post-Pubertal Children.

Selenium is involved in many metabolic pathways that are critical for life. Information concerning the metabolic effects of selenium in autism spectrum disorder (ASD) and obesity is still conflicting and incomplete. The pre- and post-pubertal selenium profiles of patients with ASD and obesity have not yet been investigated. The goal of the study was to examine selenium content before and after puberty in euthyroid children diagnosed with ASD, compared to age-matched neurotypical controls, with respect to overweight or obesity as a co-existing pathology. Serum, toenail, and 24h urine selenium levels were determined by inductively coupled plasma mass spectrometry in 287 prepubertal children (mean age 8.09 years), divided into groups: ASD with overweight/obesity (ASD+/Ob+); ASD without overweight/obesity (ASD+/Ob-); non-ASD with overweight/obesity (ASD-/Ob+); and non-ASD without overweight/obesity (ASD-/Ob-). The assessment was repeated in 258 of the children after puberty (mean age 14.26 years).The lowest serum (p < 0.001), urine (p < 0.001) and toenail (p < 0.001) selenium levels before and after puberty were observed in ASD+/Ob+ patients, and the highest in ASD-/Ob-. There were no differences in serum/toenail selenium levels between ASD+/Ob- and ASD-/Ob+ groups. The presence of ASD was associatedwith lower serum (p < 0.001) and toenail (p < 0.001) selenium in BMI-matched groups. In neurotypical patients, post-pubertal serum selenium levels were lower (p < 0.001) than pre-pubertal levels. In the multiple linear regression analyses, selenium levels showed inverse relationships with BMI (p < 0.001) and male gender (p < 0.001), irrespective of the sample type. The serum (p = 0.002) and toenail (p < 0.001) selenium levels were inversely associated with the presence of ASD. ASD, obesity/overweight, and male gender have independent impacts on selenium levels in children. Puberty may affect selenium content in neurotypical children of both genders, but not in ASD patients.

Leptin and Ghrelin in Excessive Gestational Weight Gain-Association between Mothers and Offspring.

Two-thirds of pregnant women exceed gestational weight gain recommendations. Excessive gestational weight gain (EGWG) appears to be associated with offspring's complications induced by mechanisms that are still unclear. The aim of this study was to investigate whether umbilical cord leptin (UCL) and ghrelin (UCG) concentrations are altered in full-term neonates born to EGWG mothers and whether neonatal anthropometric measurements correlate with UCL and UCG levels and maternal serum ghrelin and leptin as well as urine ghrelin concentrations. The study subjects were divided into two groups, 28 healthy controls and 38 patients with EGWG. Lower UCL and UCG levels were observed in neonates born to healthy mothers but only in male newborns. In the control group UCG concentrations correlated positively with neonatal birth weight, body length and head circumference. In the control group maternal serum ghrelin levels correlated negatively with neonatal birth weight, body length and head circumference as well as positively with chest circumference. In the EGWG group UCG concentrations correlated negatively with neonatal birth weight and birth body length. UCL correlated positively with birth body length in EGWG group and negatively with head circumference in the control group. In conclusion, EGWG is associated with disturbances in UCL and UCG concentrations.

Fatty Acid-Binding Protein 4-An "Inauspicious" Adipokine-In Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain and Gestational Diabetes Mellitus.

The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

Ghrelin in Serum and Urine of Post-Partum Women with Gestational Diabetes Mellitus.

Women with a previous history of gestational diabetes mellitus (GDM) have a significantly increased risk of developing type 2 diabetes, obesity, and cardiovascular diseases in the future. The aim of the study was to evaluate ghrelin concentrations in serum and urine in the GDM group in the early post-partum period, with reference to laboratory results, body composition, and hydration status. The study subjects were divided into two groups, that is, 28 healthy controls and 26 patients with diagnosed GDM. The maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. The concentrations of ghrelin in the maternal serum and urine were determined via enzyme-linked immunosorbent assay (ELISA). The laboratory and BIA results of the mothers with GDM were different from those without GDM. Urine ghrelin positively correlated with serum ghrelin and high-density lipoprotein cholesterol (HDL) levels in healthy mothers. There were direct correlations between urine ghrelin and HDL as well as triglycerides levels in the GDM group. Neither the lean tissue index nor body cell mass index were related to the serum ghrelin concentrations in this group. Only the urine ghrelin of healthy mothers correlated with the fat tissue index. Our results draw attention to urine as an easily available and appropriable biological material for further studies.

Heat Shock Proteins as a Potential Therapeutic Target in the Treatment of Gestational Diabetes Mellitus: What We Know so Far.

Gestational diabetes mellitus (GDM) is a complex condition that involves a variety of pathological mechanisms, including pancreatic ß-cell failure, insulin resistance, and inflammation. There is an increasing body of literature suggesting that these interrelated phenomena may arise from the common mechanism of endoplasmic reticulum (ER) stress. Both obesity-associated nutrient excess and hyperglycemia disturb ER function in protein folding and transport. This results in the accumulation of polypeptides in the ER lumen and impairs insulin secretion and signaling. Exercise elicits metabolic adaptive responses, which may help to restore normal chaperone expression in insulin-resistant tissues. Pharmacological induction of chaperones, mimicking the metabolic effect of exercise, is a promising therapeutic tool for preventing GDM by maintaining the body's natural stress response. Metformin, a commonly used diabetes medication, has recently been identified as a modulator of ER-stress-associated inflammation. The results of recent studies suggest the potential use of chemical ER chaperones and antioxidant vitamins as therapeutic interventions that can prevent glucose-induced ER stress in GDM placentas. In this review, we discuss whether chaperones may significantly contribute to the pathogenesis of GDM, as well as whether they can be a potential therapeutic target in GDM treatment.

Serum Heat Shock Protein 90 Alpha: A New Marker of Hypertension-Induced Endothelial Injury?

BACKGROUND: Hypertension-induced endothelial dysfunction is associated with an impaired bioavailability of nitric oxide regulated through interactions between nitric oxide synthase and heat shock protein-90 (Hsp-90). The role of Hsp-90 in the development of arterial hypertension remains unclear. OBJECTIVES: The objective of the study was to evaluate serum concentrations of Hsp-90a in patients with arterial hypertension in comparison to their normotensive counterparts. MATERIAL AND METHODS: The study was performed on 49 adults (mean age 55.6 years) with an elevated waist circumference. The individuals presented no subjective feeling of any disease, admitted no drug treatment for any condition, and had not previously been diagnosed with the metabolic syndrome. Patients were screened for arterial hypertension and other component disorders of the metabolic syndrome. Hsp-90a concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Twenty-eight subjects were diagnosed with arterial hypertension, while 21 individuals had normal blood pressure. Twenty-five patients satisfied the metabolic syndrome diagnostic criteria. Hsp-90a concentrations were significantly higher (p = 0.002) in the individuals with arterial hypertension than in their normotensive counterparts (median ± interquartile range): 19.42 ng/mL ± 5.17 vs. 16.86 ng/mL ± 3.18. The concentrations of Hsp-90a correlated positively with systolic blood pressure (R = 0.39; p = 0.005) and diastolic blood pressure (R = 0.29; p = 0.046). CONCLUSIONS: An increase in Hsp-90a concentrations in patients with arterial hypertension may be a compensatory mechanism for the impaired bioavailability of nitric oxide. The role of Hsp-90a as an early marker of hypertension-associated endothelial injury should be confirmed in further studies on a larger group of patients.

Overweight, obesity and cognitive functions disorders in group of people suffering from mental illness. / Nadwaga i otylosc a zaburzenia funkcji poznawczych w grupie osób chorujacych psychicznie.

OBJECTIVES: The aim of this study was to examine whether obesity affects cognitive functions in people suffering from mental illness. METHODS: 91 persons suffering from mental illness, including 51 women and 40 men took part in the study. Mean age of patients was 46 years. These persons were under constant psychiatric care, they were the participants of the daily support centre. Overweight and obesity was measured by Body Mass Index (BMI). Abdominal obesity was measured according to IDF guidelines and waist-hip ratio (WHR). Cognitive functions were examined using STMS, Verbal Fluency Test and Rey Auditory Verbal Test. RESULTS: Abdominal obesity was diagnosed in 70% of patients according to IDF guidelines and in 61% according to WHR, in women these results were respectively: 83% and 94%, while in men 62% and 32%. BMI distribution in the study group was respectively: obesity class II - 5 persons (5%), obesity class I - 26 persons (28%), overweight - 32 persons (35%), correct BMI - 27 persons (30%), underweight - 1 person (2%). There was a negative correlation between WHR, waist circumference and abstract reasoning, direct memory and delayed memory. BMI and body mass correlated negatively only with delayed memory. Number of medications taken by the studied persons showed a positive correlation with body mass and waist circumference. Negative correlations between cognitive functions and body mass, overweight and abdominal obesity was observed in women. In men these correlations were not observed, there were only correlations between cognitive functions and age. CONCLUSIONS: Obesity contributes to a decline in cognitive functions especially in direct memory and abstract reasoning.

An Interplay between Obesity and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia.

Mental illness and metabolic syndrome--a literature review.

INTRODUCTION AND OBJECTIVE: Researchers' opinions are divided on whether metabolic syndrome is a separate clinical entity. Undoubtedly, the components of the syndrome, such as abdominal obesity, hypertension, impaired glucose tolerance, hypertriglyceridaemia, adversely affect metabolism, bringing with it a number of consequences, including type 2 diabetes and cardiovascular disease which significantly impair the quality of life. ABBREVIATED DESCRIPTION OF THE STATE OF KNOWLEDGE: In recent years, much attention has been paid to research on the prevalence of metabolic disorders in mentally ill patients. This is due to a growing awareness that some antipsychotic medications contribute to weight gain in patients suffering from mental illness, and consequently lead to the development of a number of interrelated somatic factors, such as abdominal obesity, impaired glucose tolerance, hypertriglyceridaemia, and hypertension. Weight gain and other metabolic syndrome components have been noticed not only in patients, but also in their families. This paper presents current research on the prevalence of metabolic syndrome in people with mental illness. An analysis of the causes of metabolic disorders in this population has been conducted, including the role of the hypothalamic-pituitary-adrenal axis and cortisol secretion in the development of components of metabolic syndrome. CONCLUSIONS: Components of the metabolic syndrome are especially observed in mentally ill people. The mechanisms of their formation are not fully understood. A large role in their formation besides the negative effects of antipsychotic medication and specific lifestyle, play a specific dysregulation of the hypothalamic-pituitary-adrenal axis. Undoubtedly, further research and analysis in this area is necessary.

Is glyburide safe in pregnancy?

The clinical recognition and adequate treatment of women with hyperglycemia during pregnancy is significant in order to reduce neonatal complications correlated with gestational diabetes mellitus (GDM). The traditional management of pregnant patients with GDM in whom diet restriction is not sufficient enough involves subcutaneous insulin administration. However, insulin therapy has several disadvantages. It is therefore highly desirable to find an effective alternative to insulin. Glyburide (also known as glibenclamide) is currently classified as Category C by the U.S. Food and Drug Administration (FDA) for use in pregnancy. Despite the fact that the FDA does not approve glyburide for the treatment of GDM, the American College of Obstetricians and Gynecologists (ACOG) recommended in 2013 that: "when pharmacologic treatment of GDM is indicated, insulin and oral medications are equivalent in efficacy, and either can be an appropriate first-line therapy". These conflicting standpoints result from published contradictory data concerning the risks and benefits of the use of glyburide for the treatment of women with GDM. In this focused review we first present the current state of knowledge about the pharmacokinetics and pharmacodynamics of glyburide, including aspects of the transplacental transport and placental metabolism of the drug, and then we comment on several clinical studies describing the use of glyburide for the treatment of women with GDM. Since the contradictory data primarily concern the transfer of glyburide across the placenta, further rigorous scientific researches focusing on this issue are required in order to develop evidence-based recommendations for the use of glyburide for the treatment of women with GDM.

The impact of substance P on the pathogenesis of insulin resistance leading to gestational diabetes.

Gestational diabetes mellitus is one of the most often medical conditions during pregnancy affecting 5-6% of all pregnancies. The etiology of gestational diabetes is not clearly understood. In obesity and diabetes mellitus type 2, abnormal insulin signaling is an important agent mediating the increase of insulin resistance. Insulin receptor substrate serine phosphorylation is a time-controlled physiological reaction in insulin signaling that has been disrupted by metabolic and inflammatory stresses to support insulin resistance. Several kinases, including inhibitor of nuclear factor ĸB kinase β (IKK β), c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and ribosomal S6 protein kinase (S6K), are activated by these stimulators of insulin resistance and phosphorylate insulin receptor substrate proteins on several serine residues in an uncontrollable method. There are an increasing number of data indicating that substance P, being one of the crucial activators of these kinases, is a potent cytokine that impairs insulin signaling. Here we discuss recent studies that expand our understanding of how substance P may contribute to the development of insulin resistance. In our opinion, there are many interesting data suggesting that substance P may be a new player in the pathogenesis of this unfavorable condition, leading not only to the development of diabetes mellitus type 2, but also gestational diabetes. Since the etiology of gestational diabetes remains unclear, there is a strong need to explore new directions, including those not directly associated with the canonical knowledge regarding this pathology.