Diabetes and Psychiatry

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample.

Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function.

Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed.

The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization.

Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity.

Erectile dysfunction (ED) is marked by a recurring incapacity to achieve or uphold a satisfactory erection during sexual activities. The study aims to increase awareness about male reproductive health, dispel misconceptions about ED and encourage physician-patient discussions. A live online poll was conducted during a 3-day webinar titled "Turning the Tide of Men's Health" organized by Viatris™ in collaboration with the Saudi Society of Family and Community Medicine and attended by healthcare professionals (HCPs) from diverse specialties. The attendees voluntarily responded to nine poll questions on adherence to ED medication, use of phosphodiesterase type 5 inhibitors (PDE5is) as cure versus management of ED and patients' challenges. The responses to the poll questions were recorded and assessed to understand the perceptions of HCPs. The poll garnered 10,423 responses from 5831 attendees on the second day of the webinar. The key findings included HCPs' perceptions that PDE5is contribute to ED management not complete cure. The respondents acknowledged that adherence to ED medications might decline on days without planned sexual activity, and long-term adherence on a daily PDE5i is exhibited by a relatively modest percentage of ED patients. The consensus among respondents was that PDE5is do not enhance or generate sexual desire, and the daily schedule of ED treatment may be burdensome for some patients. The findings from this poll offer insights into the perspectives of HCPs regarding the usage of PDE5is to treat ED. Responders of the poll generally agreed that PDE5is can help manage ED without affecting desire, though adherence may be lower on days without planned sexual activity. Furthermore, most respondents acknowledged that adhering to a daily pill regimen posed a greater burden than waiting for the medication to take effect.

Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). US management guidelines suggest their use in patients with persistent abdominal pain but their specific effect on this symptom has not been assessed systematically.

Glucagon-like-peptide 1 receptor agonists (GLP-1RA) have transformed type 2 diabetes (T2D) and obesity management. Multiple regulatory agencies are investigating reported associations between GLP1-RA and increased suicide attempts (SA), but observational data may be prone to confounding. Randomised control trials (RCT) of GLP-1RA were largely undertaken in people at lower risk of SA. Real-world data suggest semaglutide use associates with reduced suicidal ideation and depression but was under-powered to statistically assess risk of SA. Mendelian randomisation (MR) leverages genetic instrument(s) to infer potential causal association between an exposure and an outcome. We undertook MR using missense variants in the gene encoding GLP1R that improve glycemia, lower T2D risk and/or lower BMI, to investigate potential causal association between GLP-1RA and SA. In people of European ancestry, MR did not find evidence genetically proxied GLP1RA increased SA in a general population cohort: (rs10305492, exposure: HbA1c, odds ratio [OR] and 95% confidence interval [CI]: 1.38, 0.41-4.62, p = .60), (rs10305492, exposure: FG, OR 1.27, 0.52-3.13, p = .60) and (rs1042044, exposure BMI, OR 0.30, 0.06-1.48) with concordant results in a multi-ancestry SA case-control cohort. In conclusion, we did not find MR evidence that increased GLP-1RA impacts SA. This awaits confirmation with RCT and real-world data.

Hypoalbuminemia associates with poor acute ischemic stroke (AIS) outcomes. We hypothesised a non-linear relationship and aimed to systematically assess this association using prospective stroke data from the Norfolk and Norwich Stroke and TIA Register. Consecutive AIS patients aged ≥40 years admitted December 2003-December 2016 were included. Outcomes: In-hospital mortality, poor discharge, functional outcome (modified Rankin score 3-6), prolonged length of stay (PLoS) > 4 days, and long-term mortality. Restricted cubic spline regressions investigated the albumin-outcome relationship. We updated a systematic review (PubMed, Scopus, and Embase databases, January 2020-June 2023) and undertook a meta-analysis. A total of 9979 patients were included; mean age (standard deviation) = 78.3 (11.2) years; mean serum albumin 36.69 g/L (5.38). Compared to the cohort median, albumin < 37 g/L associated with up to two-fold higher long-term mortality (HR; 95% CI = 2.01; 1.61-2.49) and in-hospital mortality (RR; 95% CI = 1.48; 1.21-1.80). Albumin > 44 g/L associated with up to 12% higher long-term mortality (HR1.12; 1.06-1.19). Nine studies met our inclusion criteria totalling 23,597 patients. Low albumin associated with increased risk of long-term mortality (two studies; relative risk 1.57 (95% CI 1.11-2.22; = 81.28)), as did low-normal albumin (RR 1.10 (95% CI 1.01-1.20; = 0.00)). Strong evidence indicates increased long-term mortality in AIS patients with low or low-normal albumin on admission.

Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial.

This study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.

The link between poor cardiovascular health (CVH), lifestyle and mild cognitive impairment (MCI) has been well established in the general population. However, there is limited research exploring these associations in ageing UK veterans.

Although the specific pathogenesis of preterm birth (PTB) has not been thoroughly clarified, it is known to be related to various factors, such as pregnancy complications, maternal socioeconomic factors, lifestyle habits, reproductive history, environmental and psychological factors, prenatal care, and nutritional status. PTB has serious implications for newborns and families and is associated with high mortality and complications. Therefore, the prediction of PTB risk can facilitate early intervention and reduce its resultant adverse consequences.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (P < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (P = 6.92 × 10) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (P < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.

Malnutrition remains a pressing health concern in developing nations, contributing to growth delay (stunting) and psychomotor impairments among the youth. Tanzania has the highest prevalence of stunting, yet the psychomotor status of its population has not been previously studied. To address this gap, we gathered anthropometric, nutritional, and psychomotor data from 211 children with the aim of assessing the reliability of digital tools as indicators of psychomotor performance in relation to the nutritional status. Collected anthropometric measures included middle-upper arm circumference (MUAC), triceps skinfold thickness (TST), and handgrip strength, while psychomotor variables were assessed using digital finger tapping test (DFTT), eye-tracking test (ETT), and nine-hole peg test (9HPT). Statistical analysis revealed significant associations between age and both MUAC and handgrip strength (R = 0.5, p < 0.001). Moreover, DFTT and 9HPT demonstrated a correlation with each other (p = 0.026) and with MUAC, handgrip strength, and age (p < 0.001). Notably, lower stature was independently linked to slower horizontal eye movements (p < 0.001). Findings underscores the crucial link between nutrition and psychomotor skills in Tanzanian children. Digital tests like DFTT, ETT, and the 9HPT show promise for assessing psychomotor performance. Addressing malnutrition requires comprehensive interventions. Future research should explore long-term effects of interventions in resource-limited settings.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

The primary objective of this randomized controlled trial (RCT) is to establish the effectiveness of time-restricted eating (TRE) compared with the Mediterranean diet for people with bipolar disorder (BD) who have symptoms of sleep disorders or circadian rhythm sleep-wake disruption. This work builds on the growing evidence that TRE has benefits for improving circadian rhythms. TRE and Mediterranean diet guidance will be offered remotely using self-help materials and an app, with coaching support.

Glucagon-like peptide-1 (GLP-1) receptor agonist-based drugs (incretin mimetics) have meaningfully impacted current treatment of type 2 diabetes mellitus (T2DM), and their actions on satiety and weight loss have led to their use as an obesity medication. With multiple pleotropic actions beyond their insulinotropic and weight loss ones, including anti-inflammatory and anti-insulin-resistant effects selectively mediated by their receptors present within numerous organs, this drug class offers potential efficacy for an increasing number of systemic and neurological disorders whose current treatment is inadequate. Among these are a host of neurodegenerative disorders that are prevalent in the elderly, such as Parkinson's and Alzheimer's disease, which have bucked previous therapeutic approaches. An increasing preclinical, clinical, and epidemiological literature suggests that select incretin mimetics may provide an effective treatment strategy, but 'which ones' for 'which disorders' and 'when' remain key open questions.

Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters.

G protein-coupled receptors (GPCRs) are relevant targets for health and disease as they regulate various aspects of metabolism, proliferation, differentiation, and immune pathways. They are implicated in several disease areas, including cancer, diabetes, cardiovascular diseases, and mental disorders. It is worth noting that about a third of all marketed drugs target GPCRs, making them prime pharmacological targets for drug discovery. Numerous functional assays have been developed to assess GPCR activity and GPCR signaling in living cells. Here, we review the current literature of genetically encoded cell-based assays to measure GPCR activation and downstream signaling at different hierarchical levels of signaling, from the receptor to transcription, via transducers, effectors, and second messengers. Singleplex assay formats provide one data point per experimental condition. Typical examples are bioluminescence resonance energy transfer (BRET) assays and protease cleavage assays (e.g., Tango or split TEV). By contrast, multiplex assay formats allow for the parallel measurement of multiple receptors and pathways and typically use molecular barcodes as transcriptional reporters in barcoded assays. This enables the efficient identification of desired on-target and on-pathway effects as well as detrimental off-target and off-pathway effects. Multiplex assays are anticipated to accelerate drug discovery for GPCRs as they provide a comprehensive and broad identification of compound effects.

The genetic composition of embryos generated by in vitro fertilization (IVF) can be examined with preimplantation genetic testing (PGT). Until recently, PGT was limited to detecting single-gene, high-risk pathogenic variants, large structural variants, and aneuploidy. Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. Despite a heated debate around this new technology, called polygenic embryo screening (PES; also PGT-P), it is already available to IVF patients in some countries. Several articles have studied epidemiological, clinical, and ethical perspectives on PES; however, a comprehensive, principled review of this emerging field is missing.

Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake.

The hypothalamus undergoes significant changes with aging and plays crucial roles in age-related metabolic alterations. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-diabetic agents that promote glucose excretion, and metabolic homeostasis. Recent studies have shown that a SGLT2i, Canagliflozin (Cana), can extend the median survival of genetically heterogeneous UM-HET3 male mice and improve central metabolic control via increases in hypothalamic insulin responsiveness in aged males, as well as reduced age-associated hypothalamic inflammation. We studied the long- and short-term effects of Cana on hypothalamic metabolic control in UM-HET3 mice. Starting the treatment from 7 months of age, we show that 4 weeks of Cana treatment significantly reduced body weight and fat mass in male but not female mice that was associated with enhanced glucose tolerance and insulin sensitivity observed by 12 months. Indirect calorimetry showed that Cana treatment increased energy expenditure in male, but not female mice, at 12 months of age. Long-term Cana treatment increased metabolic rates in both sexes, and markedly increasing formation of both orexigenic and anorexigenic projections to the paraventricular nucleus of the hypothalamus (PVH) mostly in females by 25 months. Hypothalamic RNA-sequencing analysis revealed increased sex-specific genes and signaling pathways related to insulin signaling, glycogen catabolic pathway, neuropeptide signaling, and mitochondrial function upregulated by Cana, with males showing a more pronounced and sustained effect on metabolic pathways at both age groups. Overall, our data provide critical evidence for sex-specific mechanisms that are affected by Cana during aging suggesting key targets of hypothalamic Cana-induced neuroprotection for metabolic control.

Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts. However, relevant information resides at differing stages across the data-lifecycle. Often, this information is defined and standardized only at publication stage, which can lead to data loss and workload increase. In this study, we developed Metadatasheet, a metadata standard based on interviews with members of two biomedical consortia and systematic screening of data repositories. It aligns with the data-lifecycle allowing synchronous metadata recording within Microsoft Excel, a widespread data recording software. Additionally, we provide an implementation, the Metadata Workbook, that offers user-friendly features like automation, dynamic adaption, metadata integrity checks, and export options for various metadata standards. By design and due to its extensive documentation, the proposed metadata standard simplifies recording and structuring of metadata for biomedical scientists, promoting practicality and convenience in data management. This framework can accelerate scientific progress by enhancing collaboration and knowledge transfer throughout the intermediate steps of data creation.

Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.

Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies.

Smoking is responsible for 80 % of cases of Chronic Obstructive Pulmonary Disease (COPD), while the prognosis is improved by smoking cessation (SC). We examined clinical factors associated with SC among smokers with COPD comparing women and men.

Due to systemic inequities, Black adolescents with type 1 diabetes are more likely to have suboptimal glycemic control and high rates of diabetes distress, but tailored interventions for this population are lacking. In primary outcomes of a randomized clinical trial, a family-based eHealth intervention improved glycemic control in Black adolescents with type 1 diabetes and elevated depressive symptoms. The present study is a secondary analysis of these clinical trial data examining the moderating effect of diabetes distress on the efficacy of the intervention.

Despite emerging public concern regarding the sleep health of military personnel over the past two decades, there remains a dearth of research examining sleep health among naval personnel assigned to sea duty. This study examined sleep metrics (e.g. fatigue, short sleep duration) and mental (e.g. posttraumatic stress disorder, depression) and physical health (e.g. type 2 diabetes, bodily pain) outcomes among naval personnel with recent sea duty (i.e. afloat) compared with naval personnel with recent shore duty (i.e. ashore). Prevalence ratios and mean differences for all outcomes were estimated and adjusted for demographic and military variables, and subsequently stratified by obesity. Sleep metrics were similar between afloat and ashore sailors except for short sleep duration, while sailors with recent shore duty had poorer physical health compared with those with recent sea duty. Stratified analyses suggested naval personnel with obesity had a higher proportion of nearly all adverse sleep-related health outcomes than those without obesity. Among participants without obesity, afloat personnel were more likely to report very short sleep (≤ 5 hours) and fewer hours of average nightly sleep, but were less likely to report physical health outcomes compared with ashore personnel. These findings suggest potential differences in sleep metrics and sleep-related health outcomes between afloat and ashore naval personnel. Additional research examining sleep outcomes using more objective measures is required to further investigate these findings, which may inform strategies to foster consolidated sleep despite environmental and occupational challenges in order to maintain high-performing naval personnel.

Metabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients.

Dog ownership has been associated with several complex traits and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through meta-analysis of 31,566 Swedish twins in five discovery cohorts and additional 65,986 European-ancestry individuals in three replication cohorts from Sweden, Norway, and the UK. Association test with >7.4 million single-nucleotide polymorphisms were meta-analyzed using a fixed effect model after controlling for population structure and relatedness. We identified two suggestive loci using discovery cohorts, which did not reach genome-wide significance after meta-analysis with replication cohorts. Single-nucleotide polymorphisms-based heritability of dog ownership using linkage disequilibrium score regression was estimated at 0.123 (CI 0.038-0.207) using the discovery cohorts and 0.018 (CI -0.002, 0.039) when adding in replication cohorts. Negative genetic correlation with complex traits including type 2 diabetes, depression, neuroticism and asthma was only found using discovery summary data. Furthermore, we did not identify any genes/gene-sets reaching even suggestive level of significance. This genome-wide association study does not, by itself, provide clear evidence on common genetic variants that influence the dog ownership among European-ancestry individuals.

Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7 min (95% limits of agreement (LoA): -37.8-107.2 min) for total sleep duration, 2.6 min for REM duration (95% LoA: -68.4-73.4 min) and 32.1 min (95% LoA: -54.4-118.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6 h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.

The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.

Angiotensin receptor blockers (ARBs) are commonly used to treat hypertension that target the hormonal system (renin-angiotensin system (RAS)), which regulates various physiological functions in the body. ARBs work by blocking the binding of angiotensin II to its receptor, thereby preventing a rise in blood pressure. These drugs not only normalize the overactivation of RAS but also provide protective effects against cardiovascular, renal, and type 2 diabetic patients. Inappropriate RAS activity has been linked to insulin resistance of type 2 diabetes. Olmesartan, as an ARB, was found to have a beneficial role in reducing postprandial glucose levels in type 2 diabetes. However, ARBs can cause side effects, prompting a search for new compounds that have fewer adverse effects. This study explores the potential of natural metabolites, specifically eugenol, gallic acid, myricetin, -cymene, quercetin, and kaempferol, as ARB inhibitors compared to the current standard, olmesartan. Using in silico studies, the binding affinity of these natural substances to the ARB receptor was evaluated. The results showed that myricetin and kaempferol had affinities higher than those of olmesartan, suggesting that they could serve as promising ARB inhibitors for hypertension treatment. These natural compounds could provide an alternative approach to conventional antihypertensive drugs, which may have fewer side effects. However, more research is needed to validate the efficacy and safety of these natural compounds as antihypertensive drugs. Further in vitro and in vivo studies are needed to confirm their effectiveness and safety. This study provides a promising starting point for future investigations into the potential of natural metabolites as alternative treatments for hypertension. The findings also highlight the importance of exploring natural alternative treatments for hypertension and the protective effects of ARBs on early stage type-2 diabetics.

Supervised machine learning models have been widely used to predict and get insight into diseases by classifying patients based on personal health records. However, a class imbalance is an obstacle that disrupts the training of the models. In this study, we aimed to address class imbalance with a conditional normalizing flow model, one of the deep-learning-based semi-supervised models for anomaly detection. It is the first introduction of the normalizing flow algorithm for tabular biomedical data.

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.

Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity.

Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.

Turner syndrome affects 50 per 100,000 females, affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and US culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: 1) diagnosis and genetics, 2) growth, 3) puberty and estrogen treatment, 4) cardiovascular health, 5) transition, 6) fertility assessment, monitoring, and counselling, 7) health surveillance for comorbidities throughout the lifespan, and 8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

Chronic stress lead to dysregulation of metabolic hormones, creating risk for obesity and type 2 diabetes. Based on previous work suggesting the potential for sexual activity to relieve psychological stress and reduce stress-related neuroendocrine activity, the present research explored sexual activity as a protective factor. We focused on chronic stress in the form of caregiving stress, comparing premenopausal mothers of a child with an autism spectrum disorder vs. a neurotypical child, in relation to metabolic hormones - insulin (and insulin resistance as assessed by HOMA), leptin, and ghrelin. Then, we explored the moderating role of sexual activity. Our results showed that high-stress mothers showed higher levels of insulin, insulin resistance, and lower levels of ghrelin compared to low-stress mothers. However, sexual activity modulated these associations such that among mothers who were sexually active (as coded from their daily diaries), no significant differences in these outcomes were observed between groups. This buffering effect of sexual activity was distinguishable from the buffering effect of physical activity and independent of global relationship satisfaction. Together, our findings provide novel evidence supporting the potential protective effects of sexual activity from chronic stress-related metabolic disease risk.

The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as a putative causal variant by leveraging our in-house 3D genomic data and public domain datasets. Using a luciferase reporter assay, we observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. We generated isogenic human embryonic stem cell lines homozygous for either rs7132908 allele to assess changes in gene expression and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. The rs7132908 obesity risk allele influenced expression of FAIM2 and other genes and decreased the proportion of neurons produced by differentiation. We have functionally validated rs7132908 as a causal obesity variant that temporally regulates nearby effector genes and influences neurodevelopment and survival.

This study aimed to determine the degree of family relations and associated socio-demographics characteristics, clinical/physical and mental disorders in type 2 diabetes mellitus in a Kenyan diabetes clinic. This study was part of a large multicentre study whose protocol and results had been published. It took place at the outpatient diabetes clinic at a County Teaching and Referral Hospital in South East Kenya involving 182 participants. We used a socio-demographic questionnaire, the Hamilton Depression (HAM-D) and PHQ-9 rating scales for depression, the MINI International Neuropsychiatric Interview (MINI; V5 or V6) for DSM-5 diagnoses, the WHO-5 Well-being scale and Problem Areas in Diabetes Scale (PAID). We extracted from the notes all physical conditions. We enquired about similar conditions in 1st and 2nd degree relatives. Descriptive, Chi-square test, Fisher's exact test, one way ANOVA, and Multinomial logistic regression analysis were conducted to test achievements of our specific aims. Of the 182 patients who participated in the study, 45.1% (82/182) reported a family history of diabetes. Conditions significantly (p < 0.05) associated with a degree of family history of diabetes were retinopathy, duration of diabetes (years), hypertension, and depressive disorder. On average 11.5% (21/182) scored severe depression (≥ 10) on PHQ-9 and 85.2% (115/182) scored good well-being (≥ 13 points). All DSM-5 psychiatric conditions were found in the 182 patients in varying prevalence regardless of relations. In addition, amongst the 182 patients, the highest prevalence was poor well-being on the WHO quality of life tool. This was followed by post-traumatic disorders (current), suicidality, and psychotic lifetime on DSM-5. The least prevalent on DSM-5 was eating disorders. Some type 2 diabetes mellitus physical disorders and depression have increased incidence in closely related patients. Overall, for all the patients, the prevalence of all DSM-5 diagnoses varied from 0.5 to 9.9%.

Depression in later life is associated with a two-fold increased risk of dementia. It is not clear to what extent potentially modifiable risk factors account for this association.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

We aimed to characterize the interplay between early life stress (ELS), metabolic syndrome (MetS), and plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system implicated in cardiometabolic diseases. We also examined the understudied intersection of ELS, physical activity and PAI-1.

Protectin DX (PDX), a specialized pro-resolving lipid mediator, presents potential therapeutic applications across various medical conditions due to its anti-inflammatory and antioxidant properties. Since type-1 diabetes mellitus (T1DM) is a disease with an inflammatory and oxidative profile, exploring the use of PDX in addressing T1DM and its associated comorbidities, including diabetic neuropathic pain, depression, and anxiety becomes urgent. Thus, in the current study, after 2 weeks of T1DM induction with streptozotocin (60 mg/kg) in Wistar rats, PDX (1, 3, and 10 ng/animal; i.p. injection of 200 μl/animal) was administered specifically on days 14, 15, 18, 21, 24, and 27 after T1DM induction. We investigated the PDX's effectiveness in alleviating neuropathic pain (mechanical allodynia; experiment 1), anxiety-like and depressive-like behaviors (experiment 2). Also, we studied whether the PDX treatment would induce antioxidant effects in the blood plasma, hippocampus, and prefrontal cortex (experiment 3), brain areas involved in the modulation of emotions. For evaluating mechanical allodynia, animals were repeatedly submitted to the Von Frey test; while for studying anxiety-like responses, animals were submitted to the elevated plus maze (day 26) and open field (day 28) tests. To analyze depressive-like behaviors, the animals were tested in the modified forced swimming test (day 28) immediately after the open field test. Our data demonstrated that PDX consistently increased the mechanical threshold throughout the study at the two highest doses, indicative of antinociceptive effect. Concerning depressive-like and anxiety-like behavior, all PDX doses effectively prevented these behaviors when compared to vehicle-treated T1DM rats. The PDX treatment significantly protected against the increased oxidative stress parameters in blood plasma and in hippocampus and prefrontal cortex. Interestingly, treated animals presented improvement on diabetes-related parameters by promoting weight gain and reducing hyperglycemia in T1DM rats. These findings suggest that PDX improved diabetic neuropathic pain, and induced antidepressant-like and anxiolytic-like effects, in addition to improving parameters related to the diabetic condition. It is worth noting that PDX also presented a protective action demonstrated by its antioxidant effects. To conclude, our findings suggest PDX treatment may be a promising candidate for improving the diabetic condition per se along with highly disabling comorbidities such as diabetic neuropathic pain and emotional disturbances associated with T1DM.

To evaluate the psychometric properties of a patient-reported outcome measure, the Automated Insulin Delivery-Benefits and Burdens Scale (AID-BBS), which was designed to assess benefits and burdens of AID use in adults with type 1 diabetes (T1D). The measure was hypothesized to have validity, reliability, and clinical utility for predicting likelihood of continued use of an AID system. A total of 217 adults with T1D (ages from 18 to 82 years) who were enrolled in an AID system research trial completed AID-BBS items at study midpoint (6 weeks) and at the end of the trial (13 weeks). Data were collected on pre-post glycemic outcomes. Participants completed other patient-reported psychosocial outcome measures (e.g., emotional well-being, diabetes distress, attitudes toward diabetes technology, diabetes treatment satisfaction) at Week 13. Likelihood of continued device use was assessed with three items at 13 weeks. Exploratory factor analysis supported a one-factor structure for each subscale (15-item benefit and 9-item burden subscale) when evaluated separately. Convergent, discriminant, and predictive validity, internal consistency, and test-retest reliability were supported. Benefit and burden subscales at week 6 predicted usage intention above and beyond device impact on glycemic outcomes, also controlling for baseline glycemic outcomes. : Findings support the AID-BBS as a psychometrically valid, reliable, and useful instrument for assessing burdens and benefits associated with AID system use in adults with T1D. The measure can be used to help health care providers set realistic expectations and proactively address modifiable burdens. Clinical Trial Registration Number: NCT04200313.

Polygenic embryo screening (PES) is a novel technology that estimates the likelihood of developing future conditions (eg, diabetes or depression) and traits (eg, height or cognitive ability) in human embryos, with the goal of selecting which embryos to use. Given its commercial availability and concerns raised by researchers, clinicians, bioethicists, and professional organizations, it is essential to inform key stakeholders and relevant policymakers about the public's perspectives on this technology.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with a complex origin, thought to involve a combination of genetic, biological and environmental factors. Insulin dysfunction has emerged as a potential factor contributing to AD pathogenesis, particularly in individuals with diabetes, and among those with insulin deficiency or undergoing insulin therapy. The intraperitoneal administration of streptozotocin (STZ) is widely used in rodent models to explore the impact of insulin deficiency on AD pathology, although prior research predominantly focused on young animals, with no comparative analysis across different age groups. Our study aimed to fill this gap by analyzing the impact of insulin dysfunction in 7 and 23 months 3xTg-AD mice, that exhibit both amyloid and tau pathologies. Our objective was to elucidate the age-specific consequences of insulin deficiency on AD pathology. STZ administration led to insulin deficiency in the younger mice, resulting in an increase in cortical amyloid-β (Aβ) and tau aggregation, while tau phosphorylation was not significantly affected. Conversely, older mice displayed an unexpected resilience to the peripheral metabolic impact of STZ, while exhibiting an increase in both tau phosphorylation and aggregation without significantly affecting amyloid pathology. These changes were paralleled with alterations in signaling pathways involving tau kinases and phosphatases. Several markers of blood-brain barrier (BBB) integrity declined with age in 3xTg-AD mice, which might have facilitated a direct neurotoxic effect of STZ in older mice. Overall, our research confirms the influence of insulin signaling dysfunction on AD pathology, but also advises careful interpretation of data related to STZ-induced effects in older animals.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide are primarily used for managing blood sugar levels in type 2 diabetes and aiding weight loss. Typically, their adverse effects are gastrointestinal, with limited exploration into their impact on mental health.

Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.

Posttraumatic stress disorder (PTSD) is associated with incident diabetes. However, past studies have often included predominantly male samples, despite important sex and gender differences in diabetes. To address this limitation, this study examined the association between PTSD and diabetes in older Veteran women, a population with a high burden of PTSD. Data were collected from 4,105 women ( = 67.4 years), participating in the Health of Vietnam-Era Veteran Women's Study (HealthViEWS; Department of Veterans Affairs Cooperative Studies Program #579). Participants completed self-report measures of demographics, health conditions, and health behaviors. Information on military service was obtained through service records. A structured clinical interview was conducted by telephone to assess current and lifetime PTSD and other mental health disorders. Weighted descriptive and logistic regression analyses were used to examine associations between PTSD and diabetes. The prevalence of diabetes was 28.4% among women with current full PTSD compared to 23.4%, 17.6%, and 17.5% for current subthreshold, remitted, and no PTSD. In unadjusted analyses, women with current full and subthreshold PTSD were 1.87 [1.49; 2.33] and 1.44 [1.11; 1.85] times more likely to have diabetes compared to women with no PTSD. Remitted PTSD was not associated with increased odds of diabetes. Effects were attenuated but remained significant after adjustment for relevant covariates. Vietnam-era women with current PTSD, including subthreshold symptoms, had a greater likelihood of diabetes compared to women without PTSD. These findings suggest that women with PTSD may benefit from increased diabetes prevention efforts.

A hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility of Apoe locus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice. Of note, postnatal administration of an APOE receptor agonist (APOE-RA) mitigates motor learning deficits and anxiety in those mice. Several molecular and electrophysiological properties essential for learning, which are altered by PAE, are restored by APOE-RA. Our human genome-wide association study further reveals that the interaction of PAE and a single nucleotide polymorphism in the APOE enhancer which chromatin is closed by PAE in mice is associated with lower scores in the delayed matching-to-sample task in children. APOE in the plasma is also reduced in PAE children, and the reduced level is associated with their lower cognitive performance. These findings suggest that controlling the APOE level can serve as an effective treatment for neurobehavioral deficits in FASD.

Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial.

Sleep is important for diabetes-related health outcomes. Using a multidimensional sleep health framework, we examined the association of individual sleep health dimensions and a composite sleep health score with hemoglobin A1c (HbA1c) and depressive symptoms among African American adults with type 2 diabetes.

To explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease.

Since we aim to test new options to find medication for cognitive disorders, we have begun to assess the effect of semaglutide and to conduct a review gathering studies that have attempted this purpose. This systematic review focuses on the cognitive effects of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), in the context of neurological and cognitive impairment. Semaglutide, a synthetic GLP-1 analog, showcased neuroprotective effects beyond metabolic regulation. It mitigated apoptosis and improved cognitive dysfunction in cerebrovascular disease, suggesting broader implications for neurological well-being. Also, studies highlighted GLP-1 RAs' positive impact on olfactory function in obese individuals with type 2 diabetes, on neurodegenerative disorders, multiple sclerosis, and endotoxemia. In order to analyze current studies that assess the impact of semaglutide on cognitive function, a literature search was conducted up to February 2024 on two online databases, MEDLINE (via PubMed) and Web of Science Core Collection, as well as various websites. Fifteen studies on mice populations and two studies on cell lines were included, analyzed, and assessed with bias-specific tools. The neuroprotective and anti-apoptotic properties of GLP-1 and its analogs were emphasized, with animal models and cell line studies demonstrating enhanced cognitive function. While promising, limitations include fewer studies, highlighting the need for extensive research, particularly in the human population. Even though this medication seems promising, there are significant limitations, one of which is the lack of studies on human subjects. Therefore, this review aims to gather current evidence.

Obesity constitutes a global health epidemic which worsens the main leading death causes such as type 2 diabetes, cardiovascular diseases, and cancer. Changes in the metabolism in patients with obesity frequently lead to insulin resistance, along with hyperglycemia, dyslipidemia and low-grade inflammation, favoring a more aggressive tumor microenvironment. One of the hallmarks of cancer is the reprogramming of the energy metabolism, in which tumor cells change oxidative phosphorylation to aerobic glycolysis or "Warburg effect". Aerobic glycolysis is faster than oxidative phosphorylation, but less efficient in terms of ATP production. To obtain sufficient ATP, tumor cells increase glucose uptake by the glucose transporters of the GLUT/SLC2 family. The human glucose transporter GLUT12 was isolated from the breast cancer cell line MCF7. It is expressed in adipose tissue, skeletal muscle and small intestine, where insulin promotes its translocation to the plasma membrane. Moreover, GLUT12 over-expression in mice increases the whole-body insulin sensitivity. Thus, GLUT12 has been proposed as a second insulin-responsive glucose transporter. In obesity, GLUT12 is downregulated and does not respond to insulin. In contrast, GLUT12 is overexpressed in human solid tumors such as breast, prostate, gastric, liver and colon. High glucose concentration, insulin, and hypoxia upregulate GLUT12 both in adipocytes and tumor cells. Inhibition of GLUT12 mediated Warburg effect suppresses proliferation, migration, and invasion of cancer cells and xenografted tumors. This review summarizes the up-to-date information about GLUT12 physiological role and its implication in obesity and cancer, opening new perspectives to consider this transporter as a therapeutic target.

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex-specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex-wise absolute mean curvature-a common estimate for cortical gyrification-in individuals with CAH (33 women and 20 men) and pair-wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly-the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women.

Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD.

Young women with type 1 diabetes are a high-risk population for eating disorders (ED). Prevention programs are lacking. In young women without diabetes, the Body Project has produced reductions in ED risk factors, ED symptoms and future ED onset. Therefore, the Body Project was adapted to type 1 diabetes, the Diabetes Body Project (DBP). In this protocol, we describe the multi-site randomized controlled trial (RCT) to evaluate efficacy of the DBP.

The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES).

To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT.

To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning.

The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort.

The impact of aging on diabetic retinopathy (DR) remains underestimated. The current study aimed to investigate the association between biological aging and DR, in contrast to chronological age (CA). Using the National Health and Nutrition Survey data from 2005 to 2008. Biological aging was evaluated through the biological age (BA) and phenotypic age (PA), which were calculated from clinical markers. DR was identified in participants with diabetes mellitus (DM) when they exhibited one or more retinal microaneurysms or retinal blot hemorrhages under retinal imaging, with or without the presence of more severe lesions. Survey-weighted multivariable logistic regression was performed, and the regression model was further fitted using restricted cubic splines. The discriminatory capability and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Based on weighted analyses, of the 3100 participants included in this study, of which 162 had DR. In the adjusted model, BA (odds ratio [OR] = 1.12, 95% CI, 1.06-1.18) and PA (OR = 1.11, 95% CI, 1.07-1.14) were associated with DR, while CA was not significantly (OR = 1.01, 95% CI, 0.99-1.03). Narrowing the analysis to DM participants and adjusting for factors like insulin showed similar results. ROC and DCA analyses indicate that BA/PA predicted DR better than CA and offer greater clinical utility. The positive association between BA/PA and DR was consistent across subgroups despite potential interactions. Biological aging heightens DR risk, with BA/PA showing a stronger association than CA. Our findings underscored the importance of timely anti-aging interventions for preventing DR.

Psychiatric medication can have adverse effects such as weight gain, which is a metabolic risk factor for the development of cardiovascular disease and diabetes. This study aimed to assess whether an IT-supported task shift from physicians to pharmacists could improve clinical guideline compliance in assessing metabolic risk factors for psychiatric patients.

Individuals with obesity who smoke cigarettes have increased risk of morbidity and mortality. The goal of the current study was to inform the development of a multiple health behavior change intervention designed to facilitate smoking cessation while also targeting weight gain.

Research linking type 2 diabetes and depression mostly relied on hospital-based diagnoses or prescription data, overlooking many outpatient diagnoses. We aimed to quantify the risks of depression in individuals newly diagnosed with type 2 diabetes, and type 2 diabetes in those newly diagnosed with depression, while exploring potential risk differences depending on age, sex, and follow-up time.

Obesity is a global pandemic associated with various cardio-metabolic and psychiatric disorders. Neurocognitive and functional deficits have been associated with several somatic and psychiatric disorders. Adiposity-related inflammation has recently emerged as a key risk factor for neurocognitive and functional impairments. This prospective transdiagnostic study aimed to investigate the role of adiposity-related inflammatory markers in neurocognitive and functional outcomes associated with weight changes.

Posttraumatic stress disorder (PTSD) is a prevalent mental health problem that increases risk of cardiovascular disease (CVD). It is not known whether gender or comorbidities modify associations between PTSD and CVD.

Hispanics/Latinos in the United States have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanics/Latinos of diverse heritages.

Background This study investigates the association between medication adherence and health-related quality of life among adults with type 2 diabetes mellitus at the Health Center of Tyrnavos community level. Materials and methods This cross-sectional study involved 125 patients with type 2 diabetes mellitus, aged 60 years and older, who were visiting community healthcare facilities. The research was conducted with a structured questionnaire that included 34 questions related to socio-demographic data, self-reported compliance, and stress. The DQOL-BCI (Diabetes Quality of Life - Brief Clinical Inventory) scale was used to measure health-related quality of life. Results A total of 125 patients with a mean (SD) age of 69.2 (8.1) years were included in the study (64 women and 61 men). Based on the results of the descriptive analysis, 88.0% reported high medication adherence. However, 66% of the participants reported having high anxiety levels, with 33.6% having difficulty controlling their anxiety. Quality of life was negatively correlated with lower medication adherence ( < 0.05). Conclusions Older age and low medication adherence are associated with lower quality of life among diabetic patients. Interventions to improve the quality of life in elderly diabetic patients should consider the effect of age and medication adherence.

Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV.

Currently, more than 55 million people around the world suffer from dementia, and Alzheimer's Disease and Related Dementias (ADRD) accounts for nearly 60-70% of all those cases. The spread of Alzheimer's Disease (AD) pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of ADRD's causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study the ER stress-associated neurocellular response and its effects on neurocellular homeostasis and neurogenesis, we modeled an ER stress challenge using thapsigargin (TG), a specific inhibitor of sarco/endoplasmic reticulum Ca ATPase (SERCA), in the induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) of two individuals from our Mexican American Family Study (MAFS). High-content screening and transcriptomic analysis of the control and ER stress-challenged NSCs showed that the NSCs' ER stress response resulted in a significant decline in NSC self-renewal and an increase in apoptosis and cellular oxidative stress. A total of 2300 genes were significantly (moderated statistics FDR-corrected -value ≤ 0.05 and fold change absolute ≥ 2.0) differentially expressed (DE). The pathway enrichment and gene network analysis of DE genes suggests that all three unfolded protein response (UPR) pathways, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF-6), and inositol-requiring enzyme-1 (IRE1), were significantly activated and cooperatively regulated the NSCs' transcriptional response to ER stress. Our results show that IRE1/X-box binding protein 1 (XBP1) mediated transcriptional regulation of the E2F transcription factor 1 () gene, and its downstream targets have a dominant role in inducing G1/S-phase cell cycle arrest in ER stress-challenged NSCs. The ER stress-challenged NSCs also showed the activation of C/EBP homologous protein (CHOP)-mediated apoptosis and the dysregulation of synaptic plasticity and neurotransmitter homeostasis-associated genes. Overall, our results suggest that the ER stress-associated attenuation of NSC self-renewal, increased apoptosis, and dysregulated synaptic plasticity and neurotransmitter homeostasis plausibly play a role in the causation of ADRD.

The relationship between diet and the management of chronic illnesses is well established. However, it is unknown the extent to which people with chronic illnesses pay attention to nutritional information and act upon the information obtained. We evaluated the menu ordering practices of adults with chronic illnesses.

This paper presents a comprehensive overview of the National Sleep Research Resource (NSRR), a National Heart Lung and Blood Institute-supported repository developed to share data from clinical studies focused on the evaluation of sleep disorders. The NSRR addresses challenges presented by the heterogeneity of sleep-related data, leveraging innovative strategies to optimize the quality and accessibility of available datasets. It provides authorized users with secure centralized access to a large quantity of sleep-related data including polysomnography, actigraphy, demographics, patient-reported outcomes, and other data. In developing the NSRR, we have implemented data processing protocols that ensure de-identification and compliance with FAIR (Findable, Accessible, Interoperable, Reusable) principles. Heterogeneity stemming from intrinsic variation in the collection, annotation, definition, and interpretation of data has proven to be one of the primary obstacles to efficient sharing of datasets. Approaches employed by the NSRR to address this heterogeneity include (1) development of standardized sleep terminologies utilizing a compositional coding scheme, (2) specification of comprehensive metadata, (3) harmonization of commonly used variables, and (3) computational tools developed to standardize signal processing. We have also leveraged external resources to engineer a domain-specific approach to data harmonization. We describe the scope of data within the NSRR, its role in promoting sleep and circadian research through data sharing, and harmonization of large datasets and analytical tools. Finally, we identify opportunities for approaches for the field of sleep medicine to further support data standardization and sharing.

This study aimed to examine patient characteristics associated with receipt of gender-affirming hormone therapy in the Veterans Health Administration (VHA).

Direct-to-onsumer telemedicine (DTCT) has become popular as an alternative to traditional care. However, uncertainties about the potential risks associated with the lack of comprehensive quality evaluation could influence its long-term development. This study aimed to assess the quality of care provided by DTCT platforms in China using unannounced standardised patients (USP) between July 2021 and January 2022. The study assessed consultation services on both hospital and enterprise-sponsored platforms using the Institute of Medicine quality framework. It employed 10 USP cases, covering conditions such as diabetes, asthma, common cold, gastritis, angina, low back pain, child diarrhoea, child dermatitis, stress urinary incontinence and postpartum depression. Descriptive and regression analyses were employed to examine platform characteristics and compare quality across platform types. The results showed that of 170 USP visits across 107 different telemedicine platforms, enterprise-sponsored platforms achieved a 100% success in access, while hospital-sponsored platforms had a success rate of only 47.5% (56/118). Analysis highlighted a low overall correct diagnosis rate of 45% and inadequate adherence to clinical guidelines across all platforms. Notably, enterprise-sponsored platforms outperformed in accessibility, response time and case management compared with hospital-sponsored platforms. This study highlights the suboptimal quality of DTCT platforms in China, particularly for hospital-sponsored platforms. To further enhance DTCT services, future studies should compare DTCT and in-person care, aiming to identify gaps and potential risks associated with using DTCT as alternatives or supplements to traditional care. The potential of future development in enhancing DTCT services may involve exploring the integration of hospital resources with the technology and market capabilities of enterprise-sponsored platforms.

Semaglutide (Ozempic), a GLP-1 receptor agonist effective in weight management, and ziprasidone (Geodon), an antipsychotic with a lower risk of metabolic side effects, are well-established in treating type 2 diabetes and schizophrenia, respectively. However, their interactions and effects on psychiatric symptoms are less understood. In this study, we report a case of a 43-year-old male with schizophrenia and diabetes with exacerbated paranoid delusions upon semaglutide administration for weight loss; symptoms peaked at higher doses and subsided after dose reduction. Concurrently, serum ziprasidone levels were significantly elevated at the dose reduction, suggesting a pharmacokinetic interaction likely due to semaglutide-induced slowed gastric emptying affecting ziprasidone's absorption and metabolism. This study illustrates the need for careful monitoring of psychiatric symptoms and drug levels when these medications are used together. Additionally, further research into their interactions to optimize treatment for patients with coexisting metabolic and psychiatric conditions is warranted.

A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response.

Ranolazine is a piperazine derivative and is indicated for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies. Visual hallucinations together with neurological symptoms have been described with ranolazine treatment. In this case report, we describe a case of an elderly diabetic patient with chronic angina pectoris who developed visual hallucinations during an acute worsening of kidney function after tolerating ranolazine well for six years. Regular monitoring of electrocardiograms, kidney function, and psychiatric and neurological adverse effects in elderly patients on ranolazine is advised.

The National Health Service (NHS) in England is currently piloting a weight loss programme for remission of newly diagnosed type 2 diabetes (T2D), where participants replace all food with low-energy nutritionally complete formula products for 12 weeks (total diet replacement, TDR) and receive behavioural support. In a clinical trial, this programme led to remission in nearly half the participants. However, this weight loss programme might also worsen disordered eating and prompt eating disorders in susceptible people. We aim to investigate if the TDR programme is non-inferior to standard care in terms of disordered eating in susceptible individuals.

To explore the goals, barriers, and facilitators set by caregivers of preschool-aged children to improve food parenting practices and household food environments.

The paradox of concurrent coronary artery disease (CAD) among patients with rheumatic and non-rheumatic valvular heart disease (RVHD; non-RVHD) is unclear. We aimed to evaluate the impact of the RVHD and non-RVHD on the prevalence of CAD and various risk factors, assess the number of diseased coronaries, clinical profile and the possible predictors of CAD in these patients, which may clarify the paradox and provide an insight for the prevention of CAD.

Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies. Appeared originally in .

The increased prevalence of visual impairment among diabetes patients has become a major global public health problem. Although numerous primary studies have been conducted to determine the prevalence of visual impairment and its associated factors among diabetes patients in Ethiopia, these studies presented inconsistent findings. Therefore, this review aimed to determine the pooled prevalence of visual impairment and identify associated factors among diabetes patients.

Barriers to attending in-person lifestyle interventions are common during pregnancy. The majority of young adults use Instagram, and pregnancy-related content abounds on this social media platform. The aims of this study were to assess interest in an Instagram-delivered gestational weight gain (GWG) intervention, examine characteristics associated with program interest, describe interest in specific program components, and to explore perceived advantages of and concerns about the proposed intervention.

A high-glucose environment is involved in the progression of diabetes mellitus (DM). This study aims to explore the regulatory effects of quercetin (QUE) on autophagy and apoptosis after myocardial injury in rats with DM. The type 2 DM rat models were constructed using low-dose streptozotocin (STZ) treatment combined with a high-carbohydrate (HC) diet . Compared with the control group, the body weight was decreased, whereas blood pressure, blood glucose, and the LVW/BW ratio were increased in the diabetic group. The results showed that the myocardial fibers were disordered in the diabetic group. Moreover, we found that the myocardial collagen fibers, PAS-positive cells, and apoptosis were increased, whereas the mitochondrial structure was destroyed and autophagic vacuoles were significantly reduced in the diabetic group compared with the control group. The expression levels of autophagy-related proteins LC3 and Beclin1 were decreased, whereas the expression levels of P62, Caspae-3, and Bax/Bcl-2 were increased in the diabetic group and . Moreover, QUE treatment alleviated the cellular oxidative stress reaction under high-glucose environments. The results of immunoprecipitation (IP) showed that the autophagy protein Beclin1 was bound to Bcl-2, and the binding capacity increased in the HG group, whereas it decreased after QUE treatment, suggesting that QUE inhibited the binding capacity between Beclin1 and Bcl-2, thus leading to the preservation of Beclin1-induced autophagy. In addition, the blood pressure, blood glucose, and cardiac function of rats were improved following QUE treatment. In conclusion, QUE suppressed diabetic myocardial injury and ameliorated cardiac function by regulating myocardial autophagy and inhibition of apoptosis in diabetes through the AMPK/mTOR signaling pathway.

Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation.

Background Sexual complications of people with diabetes mellitus (DM) are often neglected by the patients as well as clinicians. The neglect is more in women due to the associated stigma and taboo. Indian studies are scanty, varied and inconsistent, regarding the impact of DM on sexual functioning in women. We studied the patterns and predictors of sexual dysfunction in women with DM. Methods We did a cross-sectional questionnaire-based study comprising 50 participants in both the study (women with DM1 and DM2) and control groups (relatives/caregivers of patients and the hospital staff), selected randomly from the medicine outpatient department from May to August 2016. Approval from the institutional ethics committee was obtained. Clinical anxiety and depression were screened using the hospital anxiety and depression scale. Sexual dysfunction was assessed through female sexual function index scale (FSFI), and predictors were assessed by correlating FSFI scores with sociodemographic and clinical parameters. Results We found that 44% of women with DM had sexual dysfunction compared with 20% in the control group (p<0.01). The pattern of sexual dysfunction was seen across the domains of desire, arousal, lubrication and orgasm. High body mass index, higher age, duration of DM, treatment with insulin and complications of DM predicted a greater degree of sexual dysfunction among women. Conclusion Sexual dysfunction is common in women with DM, irrespective of the type of DM and coexisting psychological factors such as depression and anxiety.

Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population.

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.

Treating comorbid depression does not always improve outcomes for people with type 2 diabetes. Evidence is lacking on potential psychological and behavioural intermediaries of the impact of depression on diabetes outcomes.

Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population.

The objectives of this study were: 1) to describe the socio-demographics and classify the chief complaints and reasons to encounter facilities of patients presenting to public healthcare facilities; 2) to explore differences in these complaints and: International Classification of Primary Care-3 (ICPC-3) groups across socio-demographic and health system levels.