A voice-based algorithm can predict type 2 diabetes status in USA adults: Findings from the Colive Voice study.

The pressing need to reduce undiagnosed type 2 diabetes (T2D) globally calls for innovative screening approaches. This study investigates the potential of using a voice-based algorithm to predict T2D status in adults, as the first step towards developing a non-invasive and scalable screening method. We analyzed pre-specified text recordings from 607 US participants from the Colive Voice study registered on ClinicalTrials.

UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.

Background: Ang-II (angiotensin II) impairs the function of the antihypertensive enzyme ACE2 (angiotensin-converting enzyme 2) by promoting its internalization, ubiquitination, and degradation, thus contributing to hypertension. However, few ACE2 ubiquitination partners have been identified, and their role in hypertension remains unknown.

Methods: Proteomics and bioinformatic analyses were used to identify ACE2 ubiquitination partners in the brain, heart, and kidney of hypertensive C57BL6/J mice of both sexes.

Sex-specific regulatory architecture of pancreatic islets from subjects with and without type 2 diabetes.

Patients with type 2 and type 1 diabetes (T2D and T1D) exhibit sex-specific differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-sequencing (scRNA-seq) and single nucleus ATAC-sequencing (snATAC-seq) with assays probing hormone secretion and bioenergetics. In non-diabetic (ND) donors, sex differences in islet cell chromatin accessibility and gene expression predominantly involved sex chromosomes.

Acute estradiol and progesterone therapy in hospitalized adults to reduce COVID-19 severity: a randomized control trial.

COVID-19 outcomes are less severe in women than men suggesting that female sex is protective. The steroids estradiol (E2) and progesterone (P4) promote anti-inflammatory immune responses and their therapeutic use for COVID-19 has been under investigation. The aim of the study was to evaluate the efficacy of a short systemic E2 and P4 combination in mitigating COVID-19 severity in hospitalized men and women.

Sex differences in circulating metabolites across glycemic status and risk of coronary heart disease.

Background: Women with type 2 diabetes (T2D) have a 50% excess risk of coronary heart disease (CHD) than men with T2D. We compared circulating metabolites and their associations with CHD in men and women across glycemic status.

Methods: We used metabolomic data (lipoproteins, fatty acids, amino acids, glycolysis, ketones, inflammation, and fluid balance) for 87,326 CHD-free UK Biobank participants.

Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.

Type 2 and type 1 diabetes (T2D, T1D) exhibit sex differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), hormone secretion, and bioenergetics. In nondiabetic (ND) donors, sex differences in islet cells gene accessibility and expression predominantly involved sex chromosomes.

Upregulation of inflammatory genes and pathways links obesity to severe COVID-19.

Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant).

Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement.

Background: Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes.

Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.

Biological sex affects the pathogenesis of type 2 and type 1 diabetes (T2D, T1D) including the development of β cell failure observed more often in males. The mechanisms that drive sex differences in β cell failure is unknown. Studying sex differences in islet regulation and function represent a unique avenue to understand the sex-specific heterogeneity in β cell failure in diabetes.

Sex hormones, sex chromosomes, and microbiota: Identification of as an estrogen-responsive microbiota.

Microbiota composition is known to be linked to sex. However, separating sex hormones and sex chromosome roles in gut microbial diversity is yet to be determined. To investigate the sex chromosome role independent of sex hormones, we used the four-core genotype mouse model.

Sex differences in energy metabolism: natural selection, mechanisms and consequences.

Metabolic homeostasis operates differently in men and women. This sex asymmetry is the result of evolutionary adaptations that enable women to resist loss of energy stores and protein mass while remaining fertile in times of energy deficit. During starvation or prolonged exercise, women rely on oxidation of lipids, which are a more efficient energy source than carbohydrates, to preserve glucose for neuronal and placental function and spare proteins necessary for organ function.

Testosterone Deficiency Promotes Arterial Stiffening Independent of Sex Chromosome Complement.

Background: Testosterone plays a vital role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health.

Sex-specific actions of estradiol and testosterone on human fibroblast and endothelial cell proliferation, bioenergetics, and vasculogenesis.

Progress toward the development of sex-specific tissue engineered systems has been hampered by the lack of research efforts to define the effects of sex-specific hormone concentrations on relevant human cell types. Here, we investigated the effects of defined concentrations of estradiol (E2) and dihydrotestosterone (DHT) on primary human dermal and lung fibroblasts (HDF and HLF), and human umbilical vein endothelial cells (HUVEC) from female (XX) and male (XY) donors in both 2D expansion cultures and 3D stromal vascular tissues. Sex-matched E2 and DHT stimulation in 2D expansion cultures significantly increased the proliferation index, mitochondrial membrane potential, and the expression of genes associated with bioenergetics (Na+/K+ ATPase, somatic cytochrome C) and beneficial stress responses (chaperonin) in all cell types tested.

Sex differences in cardiometabolic biomarkers during the pre-diabetes stage.

Using two large prospective epidemiological studies in the U.S., we examined biomarkers that reflect sex-specific pathophysiological pathways to cardiovascular complications among people with pre-diabetes.

Estetrol Is Safe and Well Tolerated during Treatment of Hospitalized Men and Women with Moderate COVID-19 in a Randomized, Double-Blind Study.

Epidemiological data suggest that the severe acute respiratory syndrome coronavirus 2 infection rate is higher in women than in men, but the death rate is lower, while women (>50 years) on menopausal hormone therapy (MHT) have a higher survival rate than those not on MHT. Classical oral estrogen enhances the synthesis of coagulation markers and may increase the risk of thromboembolic events that are common in coronavirus disease 2019 (COVID-19). The favorable hemostatic profile of estetrol (E4) might be suitable for use in women who are receiving estrogen treatment and contract COVID-19.

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells.

Sex Differences in Cardiovascular Risk Associated With Prediabetes and Undiagnosed Diabetes.

Introduction: Women with Type 2 diabetes (T2D) face up to 50% higher risk of cardiovascular disease than men. This study evaluated the extent to which prediabetes and undiagnosed T2D are associated with a greater excess risk of cardiovascular disease in women versus in men.

Methods: Data were pooled from 18,745 cardiovascular disease-free individuals from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study.

Association Between Metabolic Syndrome Inflammatory Biomarkers and COVID-19 Severity.

Context: Metabolic syndrome (MetS) is associated with increased risk of severe COVID-19. MetS inflammatory biomarkers share similarities with those of COVID-19, yet this association is poorly explored.

Objective: Biomarkers of COVID-19 patients with and without MetS, the combination of diabetes, hypertension, obesity, and/or dyslipidemia, were analyzed to identify biological predictors of COVID-19 severity.

Sex differences in prognostic role of fasting glucose, Oral glucose tolerance, and HbA1c in diabetic cardiovascular disease.

Fasting glucose‐defined prediabetes and undiagnosed diabetes based on the American Diabetes Association criteria were associated with a greater risk of coronary heart disease, stroke, and composite atherosclerotic cardiovascular disease in women. In contrast, oral glucose tolerance‐defined prediabetes and undiagnosed diabetes were associated with a greater risk of all cardiovascular outcomes in men. Intermediate A1c was associated with a more pronounced effect on the risk of coronary heart disease and stroke in women, whereas the above diagnostic level of A1c was associated with a higher magnitude of coronary heart risk in undiagnosed men but a higher magnitude of stroke risk in undiagnosed women.

Effect of menopausal hormone therapy on COVID-19 severe outcomes in women - A population-based study of the US National COVID Cohort Collaborative (N3C) data.

Whether menopausal hormone therapy (MHT) lessens the severity of COVID-19 among women is unclear. Leveraging a U.S.

Rising Prediabetes, Undiagnosed Diabetes, and Risk Factors in Young Women.

Introduction: Women of reproductive age are less prone to cardiovascular disease than men. However, diabetes mellitus negates this female advantage. The prevalence change of prediabetes (prediabetes mellitus) and diabetes mellitus and diabetes mellitus‒associated cardiovascular risk factors have not been clearly described in women before menopause.

Gender differences in health protective behaviours and its implications for COVID-19 pandemic in Taiwan: a population-based study.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored.