Diabesity is a modern epidemic that indicates a strong association between obesity and diabetes. Key enzymes have been identified in the development and progression of both diseases, DPP-IV in glucose uptake and FAS in fatty acid synthesis. In both cases, the molecular mechanisms of how each one acts separately have been described, and which are the key inhibitory drugs and molecules for each one. However, although it is known that there is an association between both clinically and molecularly, the mechanism has not been elucidated; therefore, this review focuses on proposing a mechanism of convergence of DPP-IV and FAS in diabesity, and the possible mode of action in which bioactive peptides obtained from plant and animal sources can inhibit these two enzymes in a similar way as drugs do.

Non-communicable diseases (NCDs) are significant public health concern globally, and the burden is disproportionately high among urban populations. This study aims to compare the social determinants, NCD risk, and NCD prevalence among different wealth categories and to determine the factors associated with hypertension, obesity, and diabetes among the urban population of Nepal.

This study used urban population data from cross-sectional STEP wise approach to NCD risk factor surveillance (STEPS) survey of 2019, resulting in a sample of 3460 individuals of 15-69 years for inclusion in the analysis. We used bivariate analysis to compare the social determinants, NCD risk and NCD prevalence among urban poor, urban middle and urban rich and multivariate logistic regression to determine the association between social determinants, NCD risks and obesity, hypertension and diabetes among urban population.

The study found significant differences in hypertension, obesity and diabetes by gender, ethnicity, education, employment, smoking habits, and cholesterol levels between the three wealth groups. Among the urban poor, low education, unemployment and smoking habits were more prevalent, while high cholesterol was more prevalent among the urban rich. The significant factors associated with overweight and obesity after Bonferroni correction included Hilly region with higher odds of overweight (AOR=2.33, 95% CI=1.45-3.75,). In contrast, being from Karnali (AOR= 0.36, 95% CI=0.22-0.58) and Sudurpaschim (AOR=0.42, 95% CI=0.26-0.66) provinces were associated with lower odds of overweight and cholesterol, while cholesterol was associated with higher odds of obesity (AOR=1.01, 95% CI=1.01-1.02). Disadvantaged janajatis had the lower odds of overweight (AOR = 0.52, 95% CI = 0.36-0.78). Factors that remained significantly associated with hypertension and pre-hypertension after Bonferroni correction included: age, with higher odds of hypertension (AOR=1.03, 95% CI=1.02-1.04); men, who had higher odds of both pre-hypertension (AOR=1.68, 95% CI=1.19-2.36) and hypertension (AOR=2.23, 95% CI=1.56-3.47). Being obese (AOR = 5.12, 95% CI = 2.95-8.87, p = 0.001) and overweight (AOR = 1.69, 95% CI = 1.19-2.39, p = 0.003) were significantly associated with hypertension. Similarly, urban population residing in the hilly region had higher odds of diabetes (AOR=6.44, 95% CI=3.31-11.10) compared to the mountain region; those living in the Tarai region had higher odds of pre-diabetes (AOR=5.07, 95% CI=2.44-10.5) and diabetes (AOR=5.96, 95% CI=3.12-19.86). Respondents with high cholesterol higher odds of both pre-hypertension (AOR=1.00, 95% CI=1.00-1.02) and hypertension (AOR=1.03, 95% CI=1.02-1.04), pre-diabetics (AOR=1.00, 95% CI=1.00-1.02) and diabetics (AOR=1.03, 95% CI=1.02-1.04).

The findings indicate significant disparities in education, employment, and lifestyle habits across wealth groups; urban poor lacked education and employment. Factors such as ecological region, province, gender and age were associated with an increased risk of various health conditions such as being overweight, pre-hypertension, pre-diabetes, and diabetes. Improved health outcomes among urban populations interventions targeting increased access to education, additional investment in specific areas where outcomes are worst, and interventions to improve equitable access to healthcare are needed.

The pandemic of obesity preceded global spread of Inflammatory Bowel diseases by almost 2 decades. A pathogenic relationship has been described between obesity and inflammatory bowel diseases, but Crohn`s disease may be selectively impacted. The role of diet in pathogenesis has also gained significant support in the last few decades. This review explores dietary relationships to account for epidemiological observations. Quantifiable indices for diets have been described including a glycemic index, inflammatory indices and levels of food processing. Meta-analyses have been published which examine each for effects on obesity and co-morbidities as well as Crohn's disease and ulcerative colitis. This review suggests that ultra-processed foods provide the best link between obesity and Crohn's disease explaining epidemiological observations. However, the other 2 types of dietary indices likely contribute to ulcerative colitis as well as to co-morbidities related to both obesity and inflammatory bowel diseases. The term ultra-processed foods cover a large number of additives and extensive work is needed to define individual or combined harmful effects. Furthermore, the interactions among the 3 main indices need clarification in order to precisely apply therapeutic diets to both diseases (obesity and inflammatory bowel disease).

This investigation explores the worldwide impact of diabetes burden associated with air pollution, drawing on data from the Global Burden of Disease Study 2021.

The influence of air pollution on diabetes burden was analyzed at global, regional, and national levels. The study considered variations across age groups and genders and explored the relationship between disease impact and the Socio-Demographic Index (SDI). Additionally, an ARIMA model was employed to predict the future incidence of diabetes burden related to air pollution until 2050.

In 2021, approximately 281.91 thousand fatalities and 12.90 million disability-adjusted life years were attributed to diabetes burden due to air pollution, featuring an age-standardized mortality rate (ASMR) of 3.3234 (95% UI, 1.9549-4.6634) and an age-standardized DALY rate (ASDR) of 148.9167 (95% UI, 86.5013-224.9116) per 100,000 individuals. There was a noticeable escalation in the disease burden over the period studied. The most severe effects were noted in individuals aged 60 and above. The data also revealed a higher disease burden among males. Forecasting suggests that while low SDI regions might see a decrease in death rates, lower-middle SDI areas could face an increase in standardized mortality rates. On a national scale, Russia, Mexico, and several African nations are predicted to experience rising diabetes burden attributable to air pollution mortality rates and age-standardized mortality rates from now to 2050. South Asia and Africa are anticipated to witness substantial growth in age-standardized death rates compared to other areas.

The results provide essential insights for developing preventive strategies for diabetes burden and measures to mitigate air pollution.

Metabolic syndrome (MetS) is increasingly viewed as a pressing concern for public health globally. The objective of this study was to compare the predictive ability of 17 anthropometric indices for the risk of MetS in Chinese residents, to explore the differences in the predictive effect of the indices between different sexes, and to identify the optimal predictive indices of MetS for men and women.

This research utilized a cross-sectional study involving 5479 residents in Shandong Province, China. According to the subjects' working curve (ROC), TyG-WHtR, TyG-WC, METS-VF, CVAI, and LAP with the area under the curve (AUC) greater than 0.850 were included in the follow-up. To explore the associations between indices and the prevalence of MetS, three logistic regression models were employed. The dose-response relationship between the indices and the risk of MetS was performed by the Restricted cubic spline (RCS) curves.

The prevalence of MetS in this study is approximately 45.56%. The multivariate logistic regression showed the predictive capacity of the TyG-WC and METS-VF for MetS was superior in males, while only METS-VF in females. Furthermore, there is a non-linear relationship between MTES-VF and MetS risk both in men and women (non-linearity p < 0.001). The potential for the risk of MetS increased when the METS-VF exceeded 6.67 in males or 6.30 in females. In addition, in the male population, TyG-WC is non-linearly related to MetS risk (non-linear p < 0.001), and the risk of MetS may increase when TyG-WC is higher than 750.40.

TyG-WC and METS-VF have a good predictive value for the risk of MetS in the Chinese male population, with TyG-WC being better than METS-VF. For females, METS-VF could be regarded as the most reliable indicator.

Transcatheter aortic valve implantation (TAVI) has emerged as an effective treatment option for patients with severe aortic stenosis, particularly in those who are not suitable candidates for open-heart surgery. While diabetes is known to be associated with a higher risk of cardiovascular diseases, the impact of diabetes on the outcomes of TAVI remains controversial.

A systematic literature search was conducted across major databases, including PubMed, Web of Science (WOS), and Google Scholar, for studies published in English over the past 20 years, up until July 2024.

A total of 10 observational studies were analyzed, revealing that diabetic patients were generally younger than non-diabetic patients. The 30-day mortality rate was lower in non-diabetics (0.03 [0.02-0.04]) compared to diabetics (0.04 [0.03-0.05]). However, the hazard ratio for death beyond 30 days in diabetics was 2.05 (95% CI: 0.91-4.60, p = 0.08), and at one year, it was 1.04 (95% CI: 0.78-1.39, p = 0.77), with neither result reaching statistical significance. Meta-regression analysis showed that non-insulin-treated diabetes was significantly associated with an increased risk of acute kidney injury (AKI) compared to non-diabetics, with a log odds ratio (LogOR) of 0.3393 (p = 0.035) in one analysis and 0.3166 (p = 0.028) in another, confirming a statistically significant increase in AKI risk.

This review highlights that while diabetes slightly increases short-term mortality after TAVI, long-term survival remains comparable to non-diabetic patients. However, non-insulin-treated diabetes significantly raises the risk of acute kidney injury (AKI), emphasizing the need for enhanced renal protection and perioperative management.

Not applicable.

Approximately 40%-60% of all amputations are lower limb amputations (LLAs) related to diabetes mellitus (DM). The importance of quality of life (QoL) is increasingly recognized as after amputation. The objective of this cross-sectional study was to compare QoL (evaluated by Berg Balance Scale, BBS) in DM patients with unilateral transtibial amputation (TTA) using prosthesis (group A) with that of patients amputated due to other causes (group B). Overall, 32 patients completed two questionnaires: the 36-Item Health Survey (SF - 36) for QoL assessment and the Trinity Amputation and Prosthesis Experience Scale-Revised (TAPES-R). In group A, patients were significantly older (P < .05) with shorter periods of prosthesis use (P < .05) and had significantly lower (P = .008) adjustment to limitation (TAPES-R). Correlations were found between BBS score and SF-36, including physical functioning (P < .001, r = 0.682), energy and fatigue (P < .001, r = 0.643) and emotional well-being (P < .001, r = 0.644). In the TAPES-R, a large negative correlation was found between BBS and activity restriction (P = .001, r = -0.595). Poorer balance ability, greater activity limitation, and worse psychosocial adjustment to the prosthesis were found in patients with unilateral TTA and DM compared to TTA prosthesis users without DM.

We aim to compare the remission of erosive esophagitis (EE) among individuals with different phenotypes based on their metabolic health and obesity status and investigate the impact of changes in metabolic health on the EE remission.

Asymptomatic adults (n = 16 845) with EE at baseline, who underwent follow-up esophagogastroduodenoscopy (EGD) were categorized into 4 groups as follows: metabolically healthy (MH) nonobese, metabolically unhealthy (MU) nonobese, MH obese, and MU obese. EE was defined as grade A or higher mucosal breaks observed using esophagogastroduodenoscopy.

During a median follow-up of 2.2 years, the remission rates of EE were 286.4/103, 260.1/103, 201.5/103, and 219.9/103 person-years in MH nonobese, MU nonobese, MH obese, and MU obese groups, respectively. Multivariate-adjusted hazard ratios (95% CI) for EE remission among the MH nonobese, MU nonobese, and MH obese groups versus that of the MU obese group were 1.30 (1.23-1.37), 1.17 (1.12-1.23), and 0.98 (0.90-1.06), respectively, whereas those of the persistent MH, progression of MH to MU, and remission of MU to MH compared with the persistent MU group were 1.37 (1.23-1.52), 1.15 (1.01-1.30), and 1.28 (1.12-1.46), respectively. Increased EE remission in the persistent MH group was consistently observed in individuals with and without obesity (or abdominal obesity).

Metabolic health and nonobesity independently and favorably impact EE remission. Maintaining normal weight and healthy metabolic status may contribute to EE remission.

Pregnancy zone protein (PZP) is an antiprotease-resistant immunosuppressant belonging to the α-macroglobulin (αM) protein family. PZP is secreted by the liver and was found to be upregulated in plasma during pregnancy. α-2-macroglobulin (Α2M) shares 71 % serial homology with PZP, but low PZP levels do not lead to increased A2M levels in pregnancy. PZP can interact with several factors such as low-density lipoprotein receptor-associated protein (LRP), transforming growth factor-β (TGF-β), 78 kDa glucose-regulated protein (GRP78), and glycoside A (GdA). PZP is involved in the development of glycolipid metabolism disorders, bronchiectasis, Alzheimer's disease (AD), rheumatoid arthritis (RA), myocardial infarction (MI) and inflammatory bowel disease (IBD). PZP is also associated with the progression of tumorigenesis such as breast cancer (BC), homologyepatocellular carcinoma (HCC), lung adenocarcinoma (LAC), and colorectal cancer (CRC). Therefore, this review analyzes the role of PZP in pathophysiology of various diseases.

Obesity is a significant global health challenge, increasing the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease. Research indicates that obese individuals, regardless of their diabetic status, have an increased risk of cardiovascular complications. Studies suggest that these patients experience impaired electrical conduction in the heart, although the underlying cause-whether due to obesity-induced fat toxicity or diabetes-related factors-remains uncertain. This study investigated ventricular action potential parameters, as well as sodium (INa) and calcium (ICa, L) currents, in Zucker fatty (ZF) rats and Zucker diabetic fatty (ZDF) rats, which serve as models for obesity and T2DM, respectively. Ventricular myocytes were isolated from 25- to 30-week-old Zucker rats. Resting and action potentials were recorded using a β-escin perforated patch clamp, while INa and ICa,L were assessed with whole-cell patch clamp methods. ZF rats exhibited higher excitability and faster upstroke velocity with greater INa density, whereas ZDF rats showed decreased INa and slower action potential upstroke. No differences in ICa,L density or voltage sensitivity were found among the groups. In summary, obesity, with or without accompanying T2DM, distinctly impacts the action potential waveform, INa density, and excitability of ventricular myocytes in this rat model of T2DM.

ELOVL6, elongation-of-very-long-chain-fatty acids 6, a crucial enzyme in lipid metabolism, primarily responsible for the elongation of carbon chains of C12-C16 saturated fatty acids. It plays a significant role in various human diseases, particularly those associated with metabolic disorders related to fatty acid synthesis, such as insulin resistance, non-alcoholic fatty liver disease, cancer, and cardiovascular diseases. Emerging research also links ELOVL6 to kidney diseases, neurological conditions such as epilepsy, and pulmonary fibrosis. The enzyme's expression is regulated by various factors including diet, oxidative stress, and circadian rhythms. For instance, a high-carbohydrate diet can promote an increase in ELOVL6 expression. This abnormality leads to an accumulation of long-chain fatty acids and lipid deposition, ultimately resulting in pathological consequences across multiple systems in the body. As a biological target, ELOVL6 holds promise for diagnostic and therapeutic applications, with future research expected to uncover its mechanisms and therapeutic potential, paving the way for novel interventions in multiple disease areas. Here, the expression regulation and function of ELOVL6 in various human diseases are reviewed. This review underscores ELOVL6 as a significant therapeutic target for human diseases, with its potential for diagnostic and therapeutic applications anticipated to drive future research and enable innovative interventions in various pathological conditions.

Tanzania, like most low- and middle-income countries, is facing an increasing prevalence of obesity in the general population, including among women of reproductive age. Excess weight pre-pregnancy is a risk factor for the onset of gestational diabetes mellitus (GDM), which is associated with several poor pregnancy outcomes. Screening for GDM, as a primary preventive measure, is not systematically done in Tanzania. This study aims to explore current practices of screening for GDM during routine antenatal care (ANC), estimate the prevalence of GDM among ANC users and compare the performance of two commonly used GDM screening algorithms. We will then explore the best ways for implementing a functional screening practice for GDM at primary level hospitals using perspectives of health care workers, health managers, and pregnant women.

This will be an observational cross-sectional study design with sequential mixed-methods approach conducted in ANC clinics of two primary level hospitals: Kisarawe District Hospital in Coast region and Mbagala Rangi Tatu Hospital in Dar es Salaam region, Tanzania. Quantitative data will be collected to determine the current structural capacity and screening practices for GDM, the prevalence of GDM among ANC users, and the sensitivity and specificity of the two recommended screening algorithms. Qualitative data will be collected through key informant interviews with health managers and pregnant women and focus group discussions with healthcare workers to understand the rationale, challenges, possible solutions and benefits of the used screening algorithm. We will also explore the meaning of screening/diagnosis to pregnant women, and propose a functional GDM screening algorithm informed by users (i.e. pregnant women, health managers and care workers).

ANC is an entry point for pregnant women to access preventive services including screening for GDM. When done appropriately, GDM screening would reduce undesired outcomes attributed to GDM also beyond the pregnancy period. Through this study we will understand the bottlenecks and propose evidence to inform feasible ways to overcome them and establish a functional and standardized GDM screening service.

An increasing prevalence of overweight and obesity across the world can lead to serious health complications. The present narrative review highlighted the results of research on obesity management affiliated to the Endocrinology and Metabolism Research Institute (EMRI), Tehran University of Medical Sciences.

All documents from the EMRI focused on obesity topics were searched using PubMed and Scopus databases up to December 2019.

EMRI research projects conducted in obesity field cover several topics including childhood obesity, epidemiology of obesity, roles of genetic factors and gut microbiota in excess weight, as well as weight management by medicinal herbs and nutritional interventions. The increasing prevalence of excess-weight in children and adults indicates that conventional weight management strategies alone are not successful in obesity control and complementary therapies including herbal medicine could be helpful. Moreover, clarifying the role of the human genome and microbiome in different responses of individuals to dietary recommendations could be effective in achieving personalized nutrition.

Further population-based studies focusing on national and international collaborations are needed to progress more practical strategies to face with obesity challenge in different age ranges.

To identify the prevalence of cardiovascular disease (CVD) and obesity in patients with type 2 diabetes (T2D) in Germany and to evaluate if antidiabetic treatment patterns varied by comorbidity status.

Patients with T2D (aged ≥18 years) were identified during the study period (2014-2020) from medical claims of 4.5 million publicly insured German residents and divided into different cohorts based on CVD and/or obesity diagnosis. Annual prevalence and incidence were estimated for each study year, while characteristics and treatments were assessed in 2020. Data were extrapolated to the German population by age and sex.

The prevalence of T2D in 2020 was 11.4%. Among patients with T2D, 53.0% had CVD, 39.3% had obesity, and 20.9% had CVD and obesity. Since 2014, CVD increased by 1.4%, obesity by 4.5%, and CVD with obesity by 2.7% in patients with T2D. The incidence of T2D in 2020 was 1.0% (42.9% had CVD, 37.9% had obesity, and 15.8% had CVD and obesity). Among the prevalent T2D population in 2020, 4.9% received glucagon-like peptide-1 receptor agonists (GLP-1RAs), 9.7% received sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 13.0% received GLP-1 RAs and/or SGLT2 inhibitors. Of those with CVD, 12.9% received GLP-1 RAs and/or SGLT2 inhibitors (without CVD, 13.2%). Of those with obesity, 19.4% received GLP-1RAs and/or SGLT2 inhibitors (without obesity, 9.0%).

In this retrospective claims database study, more than two thirds of patients with T2D also had CVD, obesity, or both CVD and obesity. GLP-1 RA and SGLT2 inhibitor use remained low.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving metabolic resistance in both primary and metastatic breast cancer, and how the unique metabolic environments in metastatic sites further complicate treatment. By targeting distinct metabolic vulnerabilities at both the primary and metastatic stages, new strategies could improve the efficacy of existing therapies and provide better outcomes for breast cancer patients.

We examine the impact of access to high-speed internet on obesity. Using 14 waves of longitudinal data from the Household, Income and Labour Dynamics in Australia (HILDA) survey and a newly constructed dataset on the rollout and adoption rate of the National Broadband Network (NBN) across Australian postcodes, we find that access to high-speed internet has a positive effect on obesity. Specifically, our preferred instrumental variable estimates, which predict the variation in timing and location of internet access upgrades, suggest that a 1 % increase in the proportion of a postcode that has access to NBN is associated with a 1.573 increase in Body Mass Index and a 6.6 percentage point increase in the probability of being obese. These results are robust to several checks and alternative specifications. We also find that sedentary behaviour and inactivity are mechanisms through which access to high-speed internet transmits to obesity.

The epidemic of obesity and metabolic syndrome has become the most serious global public health problem. The part played by microRNA (miRNA) in the onset and progression of obesity and metabolic syndrome has been increasingly focused upon. The goal of this study was to explore miR-335-5p as a potential predictive biomarker or therapeutic target for obesity and metabolic syndrome. The expression level of miR-335-5p was detected by qRT-PCR. The diagnostic value of miR-335-5p was evaluated by ROC curve. The association between serum miR-335-5p levels and various clinical parameters was assessed using the chi-square test. Logistic regression analysis was used to evaluate the risk factors of metabolic syndrome in obese population. The biological processes and molecular mechanisms are studied through GO and KEGG enrichment analysis. The ROC curve analysis revealed that miR-335-5p could serve as a predictive indicator for the development of obesity accompanied by metabolic syndrome. Logistic regression analysis revealed that BMI, TG, FBG, HOMA-IR, and miR-335-5p expression represent independent risk factors of metabolic syndrome occurrence. Chi-square test analysis revealed that patients with higher values of BMI, SBP, DBP, TG, FBG, and HOMA-IR exhibited a more significantly increased expression of miR-335-5p in their serum. In conclusion, miR-335-5p holds predictive and diagnostic value for obesity and metabolic syndrome and has potential to serve as a biomarker for these conditions.

Metabolic dysfunction associated fatty liver disease (MAFLD) is a prevalent condition in patients with type 2 diabetes mellitus (T2DM). Isthmin-1 (ISM1) is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Although ISM1 has been shown to be associated with T2DM, its role in patients with MAFLD and metabolic syndrome (MetS) remains insufficiently examined. This study aimed to investigate the relationship between serum ISM1 and MAFLD in patients with T2DM and the potential involvement of MetS in this association.

A total of 250 participants were divided into four groups: 60 patients with T2DM and MAFLD, 60 with newly diagnosed T2DM, 60 with MAFLD, and 70 healthy controls. Serum ISM1 levels were measured using ELISA. The distribution of ISM1 concentration in the combined data was divided into quartiles, and the Cochran-Armitage trend test was performed to estimate the significant trends across increasing quartiles.

Compared with the controls, patients with coexisting MAFLD, MetS, and T2DM exhibited significantly elevated serum ISM1 concentrations. Serum ISM1 levels in the overweight/obese group were also higher than those in the lean group. Serum ISM1 levels were positively correlated with body mass index (BMI), uric acid, alanine aminotransferase, aspartate aminotransferase, total cholesterol (TC), low-density lipoprotein cholesterol, fasting insulin, and homeostasis model assessment of insulin resistance and negatively associated with age and high-density lipoprotein cholesterol (HDL-C). BMI, TC, and HDL-C were independently associated with serum ISM1 concentration. The relative risks for MAFLD, T2DM, and T2DM with MAFLD increased significantly with higher ISM1 quartiles. Furthermore, a positive correlation was observed between serum ISM1 levels and the number of MetS components, with the elevated plasma levels of ISM1 escalating the risk of developing MetS to some extent.

The combination of ISM1 with TG and UA was identified as the best predictive factor for diagnosing MAFLD and MetS, potentially due to their contribution to aggravating the metabolic state.

Off-label use of semaglutide for non-diabetic weight loss (which regulators have linked to social media promotion) created worldwide supply shortages. We evaluated worldwide semaglutide interest measured by online search behavior to gauge social media and conventional print media reporting's effect on search interest.

Using Google Trends Extended for Health (GTEH) multiple sampling, we retrieved regional online interest (ROI) for all countries and extracted timelines and top search queries for January 2021-August 2023 for countries with median ROI ≥ 20 using the "semaglutide" topic. We obtained semaglutide media reporting from the ProQuest database. We estimated the effect of media and within-country semaglutide interest on between-country interest with Granger causality analysis. We determined changepoints for trends within each country with joinpoint regression. We determined prominent themes in search queries for each country with natural language processing thematic analysis.

Twenty-seven countries were included. Most countries showed an increase in semaglutide interest over time, with Canada and the USA showing the largest sustained interest. Most of the search interest arose from 2022 onwards. Granger's analysis showed that media coverage could only partially explain interest, and interest in some countries partially preceded interest in others, with the UK and Germany showing strong relationships between news reports and lagged search interest. Joinpoint analysis identified up to four significant within-country changepoints. Most countries showed significant positive weekly trends in 2021-2022, although uptrends in search interest varied considerably between countries. One episode of the Dr. Oz show (TV media event) coincided with strong peaks in numerous countries. Natural language processing of top search queries showed some agreement between countries and country-specific themes. Weight loss was a major theme in most countries, while a diabetes theme was generally absent or weak. Some countries (Australia, Chile, South Africa, UK) had themes for buying Ozempic from (named) local retailers, and Germany had a theme related to buying Ozempic without a script.

GTEH data provided insights into global search interest in semaglutide and regional variation. Studies focusing on specific countries which include social media data can elucidate specific drivers behind the surge in off-label use of semaglutide.

Objectives The prevalence of chronic diseases among immigrants varies across different ethnic groups attributed to the disparities in their risk factors. This study aimed to explore the prevalence and correlates of chronic diseases among the rapidly growing South Asian population in Australia. Methods An online survey was administered (2020-2021) among South Asian immigrants in Australia. Diagnosed chronic diseases, smoking habits, physical activity, alcohol consumption, body mass index, and fruit and vegetable intake were assessed. A multivariable logistic regression model was used to examine factors associated with chronic disease. Results Overall, 50% of the study participants had one chronic disease and 39% had more than one chronic disease (n =282). Back pain (30%), depression (22%), diabetes (21%), hypertension (19%), and heart disease (12%) were the most reported diseases. Approximately 78% of participants were insufficiently active and 38% regularly consumed alcohol. Approximately three-quarters consumed fruits and vegetables less than once per day. Multivariable analyses showed that those who were aged more than 50years (OR=4.38, 95% CI 1.66-11.56), consumed alcohol more than once/month (OR=3.25, 95% CI 1.17-8.96), and ate less than one serving of vegetables/day (OR=2.94, 95% CI 1.19-7.26) had higher odds of having two or more chronic diseases. Conclusions Fifty percent of study participants presented with preventable diseases, signifying a substantial health burden. Public health interventions should primarily focus on reducing alcohol intake and increasing fruit and vegetable consumption, particularly among individuals of advanced age, to reduce the overall burden on the healthcare system.

To evaluate the prevalence of chronic comorbidities according to BMI classes and assess the interplay between excess body weight and blood glucose abnormalities in increasing the risk of major chronic diseases.

The study is based on data from the Health Search/IQVIA Health LPD Longitudinal Patient Database, an Italian general practice registry, with data obtained from electronic clinical records of 800 general practitioners throughout Italy. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2 and 3) and glucose metabolism status (normoglycemia-NGT; impaired fasting glucose-IFG; diabetes mellitus-DM). Comorbidities were identified through ICD-9 CM codes.

Data relative to 991,917 adults were analyzed. The prevalence of overweight was 39.4%, while the prevalence of obesity was 11.1% (class 1: 7.9%, class 2: 2.3%, class 3: 0.9%). In the whole population, the prevalence of DM and IFG was 8.9% and 4.2%, respectively. Both overweight and obesity were associated with an increasing prevalence of glucose metabolism alterations and a large array of different chronic conditions, including cardio-cerebrovascular diseases, heart failure, chronic kidney disease, osteoarticular diseases, depression, sleep apnea, and neoplasms of the gastrointestinal tract. Within each BMI class, the presence of IFG, and to a greater extent DM, identified subgroups of individuals with a marked increase in the risk of concomitant chronic conditions.

Addressing the double burden of excess weight and hyperglycemia represents an important challenge and a healthcare priority.

Obesity has emerged as a major health risk on a global scale. Hinokiflavone (HF), a natural small molecule, extracted from plants like cypress, exhibits diverse chemical structures and low synthesis costs. Using high-fat diet-induced obese mice models, we found that HF suppresses obesity by inducing apoptosis in adipose tissue. Adipocyte apoptosis helps maintain tissue health by removing aging, damaged, or excess cells in adipose tissue, which is crucial in preventing obesity and metabolic diseases. We found that HF can specifically bind to insulin-like growth factor 2 mRNA binding protein 2 to promote the stability of N6-methyladenosine-modified Bim, inducing mitochondrial outer membrane permeabilization. Mitochondrial outer membrane permeabilization leads to Caspase9/3-mediated adipocyte mitochondrial apoptosis, alleviating obesity induced by a high-fat diet. The proapoptotic effect of HF offers a controlled means for weight loss. This study reveals the potential of small molecule HF in developing new therapeutic approaches in drug development and biomedical research.

Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes.

593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan-Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes.

The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted.

Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT.

Alkannin is a plant-derived naphthoquinone that is isolated from the Boraginaceae family plants. In our previous studies, we found that shikonin, which is the R-enantiomer of alkannin, has potent antidiabetic activity by inhibiting the action of the aldose reductase (AR) enzyme and the protein-tyrosine phosphatase 1B (PTP1B). Therefore, in this study, we aim to explore the antidiabetic effect of alkannin targeting PTP1B and AR by employing in silico and in vitro techniques. For in silico, we used different parameters such as ADMET analysis, molecular docking, MD simulation, Root Mean Square Deviation (RMSD), protein-ligand mapping, and free binding energy calculation. The in vitro evaluation was done by assessing the inhibitory activity and enzyme kinetics of PTP1B and AR inhibition by alkannin. The in silico studies indicate that alkannin possesses favorable pharmacological properties and possesses strong binding affinity for diabetes target proteins. Hydrogen bonds (Val297, Ala299, Leu300, and Ser302) and hydrophobic interactions (Trp20, Val47, Tyr48, Trp79, Trp111, Phe122, Trp219, Val297, Cys298, Ala299, Leu300, and Leu301) are established by the compound, which potentially improves specificity and aids in the stabilization of the protein-ligand complex. The results from in vitro studies show a potent dose-dependent PTP1B inhibitory activity with an IC50 value of 19.47 μM, and toward AR it was estimated at 22.77 μM. Thus, from the results it is concluded that a low IC50 value of alkannin for both PTP1B and AR along with favorable pharmacological properties and optimal intra-molecular interactions indicates its utilization as a potential drug candidate for the management of diabetes and its end complications.

The global burden of cardiometabolic renal disease is increasing, particularly in underserved communities. Twinepidemic Inc.'s Galvanize Healthy Living program conducts community screenings, risk assessments, and educational interventions globally. We screened 1209 subjects for cardiovascular-kidney-metabolic syndrome, assessing their disease knowledge and self-confidence. Mean age was 50, with 65% females and 35% males. Imaging post-risk assessment revealed abnormalities: EKG (16%), echocardiogram (10%), carotid plaque (9%), ABI (2.5%), and eye exam (3.6%, including 8 retinopathies, 14 cataracts). New onset DM was found in 8%, prediabetes in 18.5%, High LDL in 4.2%, low HDL in 40.2%, high triglycerides in 13.1%, and abnormal BP in 38%. In addition, 18.2% were reclassified to a higher category of risk levels after imaging. Significant improvements in knowledge and self-empowerment (all p < 0.001) were seen after educational interventions. This study underscores early risk assessment's potential to enhance health outcomes globally for underserved populations, validating POC imaging and emphasizing the role of accessible care and education in patient engagement and empowerment.

Inflammation is the body's non-specific response to injury or infection. It is a natural defense mechanism that helps to maintain homeostasis and promotes tissue repair. However, excessive inflammation can lead to cellular, tissue, or organ dysfunction, as well as contribute to the development of acute vascular events and diseases like Crohn's disease, psoriasis, obesity, diabetes, and cancer. The initial response to injury involves the activation of platelets and coagulation mechanisms to stop bleeding. This is followed by the recruitment of immune cells and the release of cytokines to promote tissue repair. Over time, the injured tissue undergoes remodeling and returns to its pre-injury state. Inflammation is characterized by the activation of inflammatory signaling pathways involving cytokines, chemokines, and growth factors. Mast cells play a role in initiating inflammatory responses. Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and nucleotide-binding domain (NOD)-like receptors (NLRs) are involved in the activation of these inflammatory pathways. Inflammasomes, which are cytoplasmic complexes, also contribute to inflammation by activating cytokines. Inflammation can also be triggered by factors like dietary components and the composition of the gut microbiota. Dysregulation of the gut microbiome can lead to excessive inflammation and contribute to diseases like atherosclerosis and irritable bowel syndrome (IBS). The immune system and gut-associated lymphoid tissue (GALT) play crucial roles in the inflammatory response and the development of conditions like colorectal cancer. Anti-inflammatory therapy can play a significant role in reducing or inducing the remission of inflammatory diseases such as Crohn's disease and ulcerative colitis. The fetal origin of adult diseases theory suggests that conditions during fetal development, such as low birth weight and maternal obesity, can influence the risk of cardiometabolic diseases later in life. All of the known risk factors associated with cardiometabolic diseases such as hypertension, excess weight, obesity, type-2 diabetes, and vascular diseases are accompanied by chronic low-grade inflammation. Inflammation seems to have a role in precipitating even acute vascular events such as heart attacks and stroke. Common markers of inflammation associated with cardiometabolic disease include interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF-α), C-reactive protein (CRP), and soluble TNF receptors such as sTNFR1 and sTNFR2. These markers serve as indicators of systemic inflammation. However, these markers are not disease-specific but provide an insight into the overall chronic inflammatory status. In fact, inflammation has been identified as a potential target for future treatments to reduce or reverse the risk of atherosclerosis-related complications. The regulation of inflammation is complex, and further research is needed to better understand its mechanisms and develop strategies for managing inflammatory disorders. In summary, inflammation is a natural response to injury or infection, but excessive or prolonged inflammation can lead to the progression of various diseases. Understanding the underlying mechanisms of inflammation is important for developing treatments and preventive measures for inflammatory disorders.

Chronic pancreatitis (CP) is a progressive inflammatory disorder associated with marked morbidity and mortality and frequently requires hospitalization. This study aimed to investigate the time trends and geographical distribution of hospital admissions, the lethality rate of CP across Brazil, and the potential relationship with social indicators and associated risk factors.

Data were retrospectively obtained from the Brazilian Public Health System Registry between January 2009 and December 2019. The prevalence and lethality rates of CP per 100,000 inhabitants in each municipality were estimated from hospitalizations to in-hospital deaths and classified by age, sex, and demographic features.

During the study period, 64,609 admissions were retrieved, and most of the patients were males (63.54%). Hospitalization decreased by nearly half (-54.68%) in both sexes. CP rates in males were higher in all age groups. The greatest reduction in admissions (- 64%) was also noted in patients ≥ 70y. CP In-hospital lethality remained stable (5-6%) and similar for males and females. Patients ≥ 70y showed the highest lethality. The greatest increase in CP lethality rates (+ 10%) was observed in municipalities integrated into metropolises, which was mainly driven by small-sized municipalities (+ 124%).

CP hospitalizations decrease in both urban and rural areas, particularly in the North, Northeast, and Central-West regions, and in those above 70 years of age, but are not correlated with lethality rates in the South. This suggests ongoing changes in the environmental and socioeconomic factors in Brazil.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of chronic diabetes mellitus and has a significant impact on quality of life. DPN typically manifests itself as a symmetrical, length-dependent sensorimotor polyneuropathy with severe effects on gait. Surface electromyography (sEMG) is a valuable low-cost tool for assessing muscle activation patterns and precise identification of abnormalities. For the present study, we used information theory methods, such as cross-correlation (CC), normalized mutual information (NMI), conditional granger causality (CG-Causality), and transfer entropy (TE), to evaluate muscle network connectivity in three population groups: 33 controls (healthy volunteers, CT), 10 diabetic patients with a low risk of DPN (LW), and 17 moderate/high risk patients (MH). The results obtained indicated significant alterations in the intermuscular coupling mechanisms due to diabetes and DPN, with the TE group showing the best performance in detecting differences. The data revealed a significant increase in information transfer and muscle connectivity in the LW group over the CT group, while the MH group obtained significantly lower values for these metrics than the other two groups. These findings highlight the sEMG coupling metrics' potential to reveal neuromuscular mechanisms that could aid the development of targeted rehabilitation strategies and help monitor DPN patients.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed.

Obesity is an important condition affecting the quality of life of numerous patients and increasing their associated risk for multiple diseases, including tumors and immune-mediated disorders. Inflammation appears to play a major role in the development of obesity and represents a central point for the activity of cellular and humoral components in the adipose tissue. Macrophages play a key role as the main cellular component of the adipose tissue regulating the chronic inflammation and modulating the secretion and differentiation of various pro- and anti-inflammatory cytokines. Inflammation also involves a series of signaling pathways that might represent the focus for new therapies and interventions. Weight loss is essential in decreasing cardiometabolic risks and the degree of associated inflammation; however, the latter can persist for long after the excess weight is lost, and can involve changes in macrophage phenotypes that can ensure the metabolic adjustment. A clear understanding of the pathophysiological processes in the adipose tissue and the interplay between obesity and chronic inflammation can lead to a better understanding of the development of comorbidities and may ensure future targets for the treatment of obesity.

Obesity and its associated metabolic diseases are increasing globally. Sedentary lifestyle, high caloric diet, and genetic predisposition are known to contribute to the onset of obesity. It is increasingly recognized that exposure to environmental chemicals such as Bisphenol A (BPA) may also play a significant role. BPA has been correlated with an array of adverse health effects, including obesity and metabolic disorders. Due to public concern, manufacturers are replacing BPA with structural analogues for which there is limited toxicological data. The objective of this study was to assess the effects of these BPA analogues on adipogenesis.

The adipogenic effects of Tetra Methyl Bisphenol F (TMBPF), Bisphenol F (BPF), Bisphenol AP (BPAP), and fluorine-9-bisphenol (BHPF) were evaluated in murine 3T3-L1 cells. The cells were treated with BPA and its analogues at concentrations from 0.01 µM to 20 µM, throughout differentiation, in the absence of Dexamethasone (Dex). Lipid accumulation, mRNA and protein levels of adipogenic markers was assessed.

We found that TMBPF, BPF and BPA increased 3T3-L1 lipid accumulation and the expression levels of adipogenic markers lipoprotein lipase (Lpl), fatty acid binding protein 4 (Fabp4) and perilipin (Plin) (1-20 µM; p < 0.05), whereas BHPF and BPAP had no effect in this model. Further, TMBPF induced adipogenesis to a greater extent than all the other chemicals including BPA (1-20 µM; p < 0.05). The effect mediated by TMBPF on expression levels of Fabp4, but not Plin, is likely mediated via peroxisome proliferator-activated receptor (PPAR) γ activation.

Of the BPA analogues tested, BPF was most similar to BPA in its effects, while TMBPF was most adipogenic. In addition, TMBPF is likely a PPARγ agonist, it is likely an obesogenic chemical and may be a metabolic disruptor.

The rising phenomenon of obesity, a major risk factor for the development and progression of type 2 diabetes, is a complex and multifaceted issue that requires a comprehensive and coordinated approach to be prevented and managed. Although novel pharmacological measures to combat obesity have achieved unprecedented efficacy, a healthy lifestyle remains essential for the long-term success of any therapeutic intervention. However, this requires a high level of intrinsic motivation and continued behavioural changes in the face of multiple metabolic, psychological and environmental factors promoting weight gain, particularly in the context of type 2 diabetes. This review is intended to provide practical recommendations in the context of a holistic, person-centred approach to weight management, including evidence-based and expert recommendations addressing supportive communication, shared decision-making, as well as nutritional and pharmacological therapeutic approaches to achieve sustained weight loss.

Obesity and diabetes are commonly associated with one another and represent a significant global health issue, with a recent surge in disease incidence. Nigella sativa, also known as black cumin, is believed to possess several health benefits, including anti-diabetic, anticancer, antioxidant, antimicrobial, and anti-obesity properties. In this study, we aimed to identify the active compounds derived from N. sativa, which can potentially inhibit key protein targets and signaling pathways associated with diabesity treatment. We employed an exhaustive in silico search, which led to the identification of 22 potential compounds. Out of these, only five hits were found to be non-toxic, including Arabic and ascorbic acids, dihydrocodeine, catechin, and kaempferol. Our analysis revealed that these hits were associated with genes such as AKT1, IL6, SRC, and EGFR. Finally, we conducted molecular docking and molecular dynamics simulations, which identified kaempferol as the best binder for AKT1 in comparison to the reference molecule. Overall, our in silico integrated pipeline provides a useful approach to identify non-toxic phytocompounds as promising drug candidates to treat diabetes and obesity.Communicated by Ramaswamy H. Sarma.

Long-term exposure to PM2.5 is known to increase the risks for diabetes and obesity, but its effects on their coexistence, termed diabesity, remain uncertain. This study aimed to investigate the associations of long-term exposure to PM2.5 and its chemical constituents with the risks for diabesity, diabetes, and obesity.

This cross-sectional study used the baseline data of a multi-center cohort, consisting of three provincially representative cohorts comprising a total of 134,403 participants from the eastern (Fujian Province), central (Hubei Province), and western (Yunnan Province) regions of China. Obesity and diabetes, and diabesity were identified by a body mass index (BMI) ≥28 kg/m2 and fasting plasma glucose (FPG) ≥126 mg/dL. The average concentrations of PM2.5 and five chemical constituents (NO3 -, SO4 2-, NH4 +, organic matter, and black carbon) over participants' residence during the past three years were estimated using machine learning models. Logistic regression models with double robust estimators, Bayesian kernel machine regression, and weighted quantile sum regression were employed to estimate independent and joint effects of PM2.5 chemical constituents on the risks for diabesity, diabetes, and obesity, as well as the differences from the effects on obesity. Stratified analyses were performed to examine effect modification of sociodemographic and lifestyle factors.

There were 129,244 participants with a mean age of 54.1 ± 13.8 years included in the study. Each interquartile range increase in PM2.5 concentration (8.53 μg/m3) was associated with an increased risk for diabesity (OR = 1.23 [1.17, 1.30]), diabetes only (OR = 1.16 [1.13, 1.19]), and obesity only (OR = 1.03 [1.00, 1.05]). Long-term exposure to each PM2.5 chemical constituent was associated with an increased risk for diabesity, where organic matter exposure, with maximum weight (48%), was associated with a higher risk for diabesity (OR = 1.21 [1.16, 1.27]). Among those with obesity, black carbon contributed most (68%) to the joint effect of PM2.5 chemical constituents on diabesity (OR = 1.16 [1.11, 1.22]). Physical activity reduced adverse effects of PM2.5 on diabesity. Also, additive rather than multiplicative effects of obesity on the PM2.5-diabetes association were observed.

Long-term exposure to PM2.5 and its chemical constituents was associated with an increased risk for diabesity, stronger than associations for diabetes and obesity alone. The main constituents associated with diabesity and obesity were black carbon and organic matter.

National Natural Science Foundation of China (42271433, 723B2017), National Key R&D Program of China (2023YFC3604702), Fundamental Research Funds for the Central Universities (2042023kfyq04, 2042024kf1024), the Science and Technology Major Project of Tibetan Autonomous Region of China (XZ202201ZD0001G), Science and technology project of Tibet Autonomous Region（XZ202303ZY0007G), Key R&D Project of Sichuan Province (2023YFS0251), Renmin Hospital of Wuhan University (JCRCYG-2022-003), Jiangxi Provincial 03 Special Foundation and 5G Program (20224ABC03A05), Wuhan University Specific Fund for Major School-level Internationalization Initiatives (WHU-GJZDZX-PT07).

Regarding the rapidly increasing prevalence of obesity throughout the globe, it remains a serious public health concern. A subgroup of obesity that does not meet metabolic syndrome criteria is called metabolically healthy obesity (MHO). However, whether the MHO phenotype increases cardiovascular disease (CVD) risk is controversial. This study aimed to evaluate the prevalence of MHO and its 10-year CVD risk in Iranian populations.

Based on the STEPS 2021 project in Iran, we collected data on 18119 Iranians 25 years and older from all 31 provinces after applying many statistical factors. Using the Framingham score, we evaluated the 10-year cardiovascular risk associated with the various MHO definition criteria for Iranian populations.

The prevalence of MHO was 6.42% (5.93-6.91) at the national level according to the AHA-NHLBI definition, and 23.29% of obese women and 24.55% of obese men were classified as MHOs. Moreover, the MHO group was younger than the metabolically unhealthy obesity (MUO) group based on all definitions (p < 0.001). The odds ratio of MUO individuals being classified as high-risk individuals by the Framingham criteria for CVD was significantly higher than that of MHO individuals by all definitions, with a crude odds ratio of 3.55:1 based on AHA-NHLBI definition.

This study reveals a significant prevalence of MHO in the Iranian population, with approximately 25% of obese individuals classified as MHO. While MHO is associated with a lower risk of cardiovascular disease compared to MUO, MHO carries the potential for transitioning to an unhealthy state.

The online version contains supplementary material available at 10.1007/s40200-023-01364-5.

We aimed to compare the risk of erosive esophagitis (EE) among individuals with different phenotypes based on metabolic health status and obesity and investigate the role of changes in metabolic health in EE risk.

A cohort of 258 892 asymptomatic adults without EE at baseline who underwent ollow-up esophagogastroduodenoscopy (EGD) were categorized into the following four groups according to metabolic health and obesity status: (i) metabolically healthy (MH) non-obese; (ii) metabolically unhealthy (MU) non-obese; (iii) MH obese; and (iv) MU obese. EE was defined as the presence of grade A or higher mucosal breaks on EGD.

During a median follow-up of 4.5 years, the incidence rates of EE were 0.6/103 person-years (PY), 1.7/103 PY, 1.7/103 PY, and 3.1/103 PY in the MH non-obese, MU non-obese, MH obese, and MU obese groups, respectively. The multivariable-adjusted hazard ratio (HR) (95% confidence intervals [CI]) for developing EE comparing the MH obese, MU non-obese, and MU obese groups with the MH non-obese group were 1.49 (1.29-1.71), 1.56 (1.25-1.94), and 2.18 (1.90-2.49), respectively. The multivariable-adjusted HR (95% CI) comparing the progression of MH to MU, regression of MU to MH, and persistent MU with the persistent MH group were 1.39 (1.10-1.76), 1.39 (1.09-1.77), and 1.86 (1.56-2.21), respectively. The increased risk of EE among the persistent MU group was consistently observed in individuals without obesity or abdominal obesity.

Metabolic unhealthiness and obesity were independent risk factors for the development of EE, suggesting that maintaining both normal weight and metabolic health may help reduce the risk of EE.

In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC). Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis. Claudin-6 overexpression is associated with an HCC aggressive phenotype and treatment resistance. Claudin-6 mAbs or chimeric antigen receptor-T cells therapies are currently being clinically investigated for Claudin-6 overexpressing tumors. In conclusion, targeting Claudin proteins offers a novel clinical opportunity for the treatment of patients with advanced liver fibrosis and HCC.

To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex.

A cross-sectional study.

A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group.

The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (β = -0.37, p = 0.002; β = -1.22, p = 0.03) and deep retinal vessel density, respectively (β = -0.66, p < 0.001; β = -1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (β = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (β = -0.50, p = 0.003).

This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences.

To prevent obesity and diabetes environmental interventions such as eliminating food deserts, restricting proliferation of food swamps, and improving park access are essential. In the United States, however, studies that examine the food and park access relationship with obesity and diabetes using both global and local regression are lacking. To guide county, state, and federal policy in combating obesity and diabetes, there is a need for cross-scale analyses to identify that relationship at national and local levels. This study applied spatial regression and geographically weighted regression to the 3,108 counties in the contiguous United States. Global regression show food deserts exposure and density of fast-food restaurants have non-significant association with obesity and diabetes while park access has a significant inverse association with both diseases. Geographically weighted regression that takes into account spatial heterogeneity shows that, among southern states that show high prevalence of obesity and diabetes, Alabama and Mississippi stand out as having opportunity to improve park access. Results suggest food deserts exposure are positively associated with obesity and diabetes in counties close to Alabama, Georgia, and Tennessee while density of fast-food restaurants show positive association with two diseases in counties of western New York and northwestern Pennsylvania. These findings will help policymakers and public health agencies in determining which geographic areas need to be prioritized when implementing public interventions such as promoting healthy food access, limiting unhealthy food options, and increasing park access.

Background: Individuals diagnosed with type 2 diabetes mellitus (T2DM) are more prone to experiencing severe cardiovascular (CV) events, often occurring at a younger age, due to a complex interplay of risk factors. T2DM diagnosis inherently classifies patients as belonging to a higher CV risk group. In light of the increased susceptibility to severe CV outcomes, our study aims to assess the distribution of CV risk categories and the attainment of therapeutic targets among Romanian patients diagnosed with T2DM. Methods: A cross-sectional analysis was performed, including 885 patients diagnosed with T2DM who were consecutively admitted to a secondary care hospital unit between January and July 2019. Data collection included demographics, lipid profile, glycated hemoglobin (HbA1c), blood pressure (BP), estimated glomerular filtration rate (eGFR), and medication specifics for T2DM and associated conditions. Patients were stratified into CV risk categories based on the ESC/EAS guidelines, encompassing moderate, high, and very high risk categories. The rationale for selecting these guidelines for CV risk categories was that they were current and provided best practice recommendations for T2DM patients during the cross-sectional evaluation. We assessed therapeutic target achievement rates for LDL-C, HbA1C, and BP for each CV risk category. Additionally, we examined utilization rates of statins and novel cardio- and reno-protective, non-insulin antidiabetic medications. Results: The group's average age was 62.9 ± 7.7 years and comprised 53.7% females. An average HbA1c level of 7.1 ± 1.3% was observed in the group. Within the cohort, 83% had hypertension, with a mean systolic BP of 132 ± 16.2 mm Hg and mean diastolic BP of 80 ± 9.6 mm Hg. Additionally, 64.6% of patients were obese, with a mean body mass index of 32.3 ± 5.3 kg/m2. Mean LDL-C levels varied across the different CV risk categories: 106.6 ± 35.6 mg/dL in the very high risk category, 113 ± 39.3 mg/dL in the high risk category, and 124.3 ± 38.3 mg/dL in the moderate risk category. Most treatment schemes included metformin (87.0%) and statins (67.0%), with variable use rates for other glucose-lowering and CV risk-modifying therapies. The percentage of patients using GLP-1 RAs was 8.1%, while 3.9% used SGLT2 inhibitors. Conclusions: Most Romanian patients with T2DM are at very high or high CV risk. Despite reaching glycemic control targets, most patients are not achieving the composite target, which includes, besides glycemic control, BP values and lipid profile. Many patients with T2DM are not benefiting from DM therapies with additional cardiorenal benefits or statins.