Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes.

Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age.

A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.

Purpose Of Review: The present study aims to review the existing literature to identify pathophysiological proteins in obesity by conducting a systematic review of proteomics studies. Proteomics may reveal the mechanisms of obesity development and clarify the links between obesity and related diseases, improving our comprehension of obesity and its clinical implications.

Recent Findings: Most of the molecular events implicated in obesity development remain incomplete.

Quantification of lipoproteins by proton nuclear magnetic resonance spectroscopy (H-NMRS) improves the prediction of cardiac autonomic dysfunction in patients with type 1 diabetes.

Aims: To assess if advanced characterization of serum glycoprotein and lipoprotein profile, measured by proton nuclear magnetic resonance spectroscopy (H-NMRS) improves a predictive clinical model of cardioautonomic neuropathy (CAN) in subjects with type 1 diabetes (T1D).

Methods: Cross-sectional study (ClinicalTrials.gov Identifier: NCT04950634).

Serum metabolomics profiling by proton nuclear magnetic resonance spectrometry of the response to single oral macronutrient challenges in women with polycystic ovary syndrome (PCOS) compared with male and female controls.

Background: The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the-art proton nuclear magnetic resonance spectrometry (H-NMRS) metabolomics profiling, that androgen excess in women induces a certain masculinization of postprandial metabolism that is modulated by obesity.

Materials And Methods: Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected to be similar in terms of age and body mass index (BMI).

Serum metabolomics profiling by proton nuclear magnetic resonance spectroscopy reveals sexual dimorphism and masculinization of intermediate metabolism in women with polycystic ovary syndrome (PCOS).

Background: The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the art proton nuclear magnetic resonance spectroscopy metabolomics profiling, that androgen excess in women induces also a certain masculinization of intermediate metabolism that is modulated by obesity.

Methods: Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected in order to be similar in terms of age and body mass index (BMI).

Validation of circulating microRNAs miR-142-3p and miR-598-3p in women with polycystic ovary syndrome as potential diagnostic markers.

Study Question: Circulating miRNAs previously associated with androgen excess in women might be used as diagnostic biomarkers for polycystic ovary syndrome (PCOS).

Summary Answer: Models based on circulating miR-142-3p and miR-598-3p expression show good discrimination among women with and without PCOS, particularly when coupled with easily available measurements such as waist-to-hip ratio (WHR) and circulating LH-to-FSH (LH/FSH) ratios.

What Is Known Already: The lack of standardization of the signs, methods, and threshold values used to establish the presence of the diagnostic criteria (hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology) complicates the diagnosis of PCOS.

Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes.

Background: Sex differences characterize cardiovascular outcomes in patients with type 1 diabetes. Cardioautonomic neuropathy is a common complication of type 1 diabetes that associates increased morbi-mortality. Data regarding the interplay between sex and cardiovascular autonomic neuropathy are scarce and controversial in these patients.

The Effect of Sex and Obesity on the Gene Expression of Lipid Flippases in Adipose Tissue.

Molecular mechanisms behind obesity and sex-related effects in adipose tissue remain elusive. During adipocyte expansion, adipocytes undergo drastic remodelling of lipid membrane compositions. Lipid flippases catalyse phospholipid translocation from exoplasmic to the cytoplasmic leaflet of membranes.

Effect of Iron Depletion by Bloodletting vs. Observation on Oxidative Stress Biomarkers of Women with Functional Hyperandrogenism Taking a Combined Oral Contraceptive: A Randomized Clinical Trial.

Women with functional hyperandrogenism show both increased markers of oxidative stress and a mild iron overload. Combined oral contraceptives (COC) may worsen redox status in the general population. Since iron depletion ameliorates oxidative stress in other iron overload states, we aimed to address the changes in the redox status of these women as a consequence of COC therapy and of bloodletting, conducting a randomized, controlled, parallel, open-label clinical trial in 33 adult women with polycystic ovary syndrome or idiopathic hyperandrogenism.

Bloodletting has no effect on the blood pressure abnormalities of hyperandrogenic women taking oral contraceptives in a randomized clinical trial.

Normoferritinemic women with functional hyperandrogenism show a mild iron overload. Iron excess, hyperandrogenism, and cardioautonomic dysfunction contribute to blood pressure (BP) abnormalities in these patients. Furthermore, combined oral contraceptives (COC) prescribed for hyperandrogenic symptoms may worse BP recordings.

Remission of Diabetes Following Bariatric Surgery: Plasma Proteomic Profiles.

Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women with severe obesity submitted to bariatric procedures, including six non-diabetic patients and eleven patients with T2D.

Postprandial responses of circulating energy homeostasis mediators to single macronutrient challenges: influence of obesity and sex hormones.

We analysed the influence of obesity, sex and sex steroids on the postprandial responses of circulating energy homeostasis mediators and their receptors to different macronutrient challenges. Seventeen women with polycystic ovary syndrome (PCOS, 8 with obesity), 17 non-hyperandrogenic control women (8 with obesity) and 19 control men (9 with obesity) were submitted, on alternate days, to isocaloric (300 kcal) oral glucose, lipid and protein loads. We evaluated serum ghrelin, leptin, soluble leptin receptor and adiponectin levels and the leukocyte gene expression of ghrelin (GHRL) and its receptor (GHSR), leptin receptor (LEPR) and adiponectin receptor 1 (ADIPOR1) during the macronutrient challenges.

Acute-phase glycoprotein profile responses to different oral macronutrient challenges: Influence of sex, functional hyperandrogenism and obesity.

Acute-phase glycoprotein H-NMR spectroscopy profiles serve as surrogate markers of chronic inflammation in metabolic disorders such as obesity, diabetes and polycystic ovary syndrome (PCOS). The latter is associated with increased height-to-width (H/W) ratios of GlycA and GlycB after fasting, but not to glycoprotein areas, regardless of obesity. We studied the responses to separate glucose, lipid and protein oral challenges of five glycoprotein variables (GlycA, GlycB, and GlycF areas and the GlycA and GlycB H/W ratios) in 17 women with PCOS, 17 control women, and 19 healthy men.

Changes in Soluble TWEAK Concentrations, but Not Those in Amyloid-β(1-40), Are Associated with a Decrease in Carotid Intima-Media Thickness after Bariatric Surgery in Obese Women.

Background/aim: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and amyloid-β(1-40) (Aβ40) emerged as markers of cardiovascular risk because of their actions in the endothelium and their role in atherosclerotic progression. The aim of this study was to analyze the association of these two factors with the decrease in carotid intima-media thickness (cIMT) after bariatric surgery in obese women.

Methods: We studied 60 severely obese women, of whom 20 were submitted to laparoscopic Roux-en-Y gastric bypass (RYGB), 20 to sleeve gastrectomy (SG), and 20 to lifestyle modification therapy.

2D Diffusion-Ordered H-NMR Spectroscopy Lipidomic Profiling after Oral Single Macronutrient Loads: Influence of Obesity, Sex, and Female Androgen Excess.

Scope: Postprandial dysmetabolism plays a major role in the pathogenesis of metabolic disorders such as obesity and the polycystic ovary syndrome (PCOS). The aim is to characterize the circulating lipoprotein particle profiles in response to oral glucose, lipid, and protein challenges.

Methods And Results: 17 women with PCOS, 17 control women, and 19 healthy men selected to have similar age and body mass index are studied.

TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones.

We studied if macronutrients of the diet have different effects on leukocyte activation, and if these effects are influenced by sex hormones or obesity. We analyzed leukocyte cell surface and gene expression of toll-like receptors 2 and 4 (TLR2 and TLR4) during fasting and after macronutrient loads in women with polycystic ovary syndrome and female and male controls. Fasting TLR2 surface expression in neutrophils was higher in men than in women.

Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex.

Scope: Cytokines have pleiotropic functions within the organism and their levels may be influenced by obesity, visceral adiposity and sex hormones. Diet composition may also affect their systemic concentrations during fasting and in the postprandial period. Hence, we studied the influence of sex steroids and obesity on the circulating levels of a panel of metabolic cytokines in the fasting state and after single macronutrient challenges.

Glycoprotein A and B Height-to-Width Ratios as Obesity-Independent Novel Biomarkers of Low-Grade Chronic Inflammation in Women with Polycystic Ovary Syndrome (PCOS).

The polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women in reproductive age. Obesity and low-grade chronic inflammation are frequently associated with PCOS. Recently, proton nuclear magnetic resonance (H-NMR)-derived glycoprotein profiles have emerged as potential biomarkers that reflect systemic inflammation in type 2 diabetes, obesity, and other pathological processes.

Androgen Excess in Women: Proteomic and Metabolomic Approaches.

Most research efforts addressing the pathophysiology of polycystic ovary syndrome (PCOS) applied targeted approaches focusing on specific genes and/or proteins that were selected on the basis of previous knowledge about their putative roles in metabolic and signalling pathways. On the contrary, the use of nontargeted approaches is not constricted by previous knowledge on the issue and offers the potential advantage of revealing novel associations with unexpected molecules that might lead to new mechanistic explanations for the etiology and the pathophysiology of PCOS. To date, several "omics" approaches have been applied to create a holistic picture complementing the information generated by genetic studies.

Postprandial inflammatory responses after oral glucose, lipid and protein challenges: Influence of obesity, sex and polycystic ovary syndrome.

Background & Aims: Most evidence linking the polycystic ovary syndrome (PCOS) with chronic low-grade inflammation has been obtained in the fasting state. We have studied the postprandial inflammatory response to oral glucose, lipid and protein challenges and the possible influences of obesity, sex and PCOS on these responses.

Methods: On alternate days, we submitted 17 women with PCOS (9 non-obese, 8 obese), 17 control women (9 non-obese, 8 obese) and 19 control men (10 non-obese, 9 obese) to isocaloric (300 Kcal) oral macronutrient loads.

Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity.

Context: Gut microbiota play a major role in health and disease by influencing physiology, metabolism, nutrition, and immune function.

Objective: To evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found.

Design: Cross-sectional study.

Non-targeted profiling of circulating microRNAs in women with polycystic ovary syndrome (PCOS): effects of obesity and sex hormones.

Purpose: Circulating micro-ribonucleic acids (miRNAs) are small noncoding RNA molecules that influence gene transcription. We conducted the present profiling study to characterize the expression of circulating miRNAs in lean and obese patients with polycystic ovary syndrome (PCOS), the most common endocrine and metabolic disorder in premenopausal women.

Basic Procedures: We selected 11 control women, 12 patients with PCOS and 12 men so that they were similar in terms of body mass index.