Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.

Diabetes mellitus is a global health issue that necessitates the development of novel therapeutic approaches. Today numerous experimental methods have been used and set up to evaluate novel drugs with antidiabetic effects. In addition, several research studies have been done to induce diabetes under in vitro and in vivo conditions, but only a small number of these efforts are currently in a usable stage. This review aims to provide useful guidance for researchers who seek to evaluate the antidiabetic potential of drugs, agents, or new medications using the standard methods published by authorities and academics worldwide organizations and research centers. In this review, we collected 132 relevant articles from prominent databases such as PubMed, ScienceDirect, Scopus and others to summarize in vitro and in vivo experimental validation of antidiabetic treatment from 1943 to present.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease, and typical pathologic findings include abnormally hyperphosphorylated tau aggregation and neurofibrillary tangles. Insulin resistance and hyperglycemia have been assessed as risk factors for AD development. As the maintenance of optimal blood glucose levels is an important indicator of diabetes mellitus (DM) treatment, diet control is essential. AMPK is a crucial sensor of cellular bioenergetics for controlling anabolic and catabolic metabolism. Diet restriction to achieve euglycemia can increase AMPK activity in the liver and heart. Since AMPK is a direct regulator of tau phosphorylation, we hypothesized that strict diet control to achieve euglycemia affects tau protein phosphorylation through increased AMPK activity in the hippocampus of DM rats. To confirm this hypothesis, we generated insulin-deficient DM rats by subtotal pancreatectomy. Animals were categorized into the restriction (R) group, control (C) group and ad libitum (AL) group according to the diet. We found that tau phosphorylation was significantly increased in the R group compared with the C or AL group. AMPK activity in the R group significantly increased compared to that of the C group or AL group, as expected. Furthermore, the R group showed more critical tau pathology in the hippocampus than the other groups. These results suggest that diet control to achieve euglycemia in insulin-deficient DM conditions is harmful because of the increased possibility of AD development through increased tau phosphorylation by AMPK activation in the hippocampus. We propose that not only hyperglycemia but also euglycemia, which is beneficial in DM patients, must be considered a potential risk factor for AD development, especially when euglycemia is achieved by diet control during insulin deficiency.

Excretion of β2-microglobulin (β2M) above 300 µg/g creatinine, termed tubulopathy, was regarded as the critical effect of chronic exposure to the metal pollutant cadmium (Cd). However, current evidence suggests that Cd may induce nephron atrophy, resulting in a reduction in the estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. Herein, these pathologies were investigated in relation to Cd exposure, smoking, diabetes and hypertension. Data were from 448 residents of Cd-polluted and non-polluted regions of Thailand. The body burden of Cd, indicated by the mean Cd excretion (ECd) normalized to creatinine clearance (Ccr) as (ECd/Ccr) ×100 in women and men did not differ (3.21 vs. 3.12 µg/L filtrate). The prevalence odds ratio (POR) for tubulopathy and a reduced eGFR were increased by 1.9-fold and 3.2-fold for every 10-fold rise in Cd body burden. In women only, a dose-effect relationship was seen between β2M excretion (Eβ2M/Ccr) and ECd/Ccr (F = 3.431, η2 0.021). In men, Eβ2M/Ccr was associated with diabetes (β = 0.279). In both genders, eGFR was inversely associated with Eβ2M/Ccr. The respective covariate- adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m2 lower in women and men who had severe tubulopathy; (Eβ2M/Ccr) ×100 ≥ 1000 µg/L filtrate. These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of Eβ2M/Ccr could be attributable mostly to Cd-induced impairment in tubular reabsorption of the protein together with Cd-induced nephron loss, evident from an inverse relationship between Eβ2M/Ccr and the eGFR.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

Background: Novel technologies like continuous glucose monitor (CGM) systems are improving diabetes management by means of real-time sensor glucose levels, retrospective course of glucose and trend arrows. Continuous Glucose Monitoring (CGM) offers real-time alerts for (prognostic) hypo- and hyperglycemia, fast dropping or increasing glucose, and hence improving glycaemia under unstable conditions like during meals, physical activity and exercise management. Complex CGM systems challenge people with diabetes and health care professionals in interpreting rapid changes, sensor delay (~10-minute difference between interstitial and plasma glucose), and malfunctions. Enhanced prediction models are necessary for optimal insulin dosing, daily activities, and especially for future fully closed-loop systems. Methods: The aim of this study was to investigate the efficacy of three different predictive models for glucose responses: 1) an autoregressive integrated moving average model (ARIMA), 2) logistic regression, 3)and long short-term memory networks (LSTM), in predicting glucose levels after 15 minutes and one hour. We compared and evaluated the performance of these models in predicting hypoglycemia (<70 mg/dL), euglycemia (70-180 mg/dL), and hyperglycemia (>180 mg/dL). In more detail, by assessing metrics such as precision, recall, F1-score, and accuracy, we specifically assessed which model provided the most accurate and reliable predictions for glucose levels Results: As expected, ARIMA showed the worst accuracy especially predicting hypoglycaemia withing 1-hour (7.3%). The accuracy of the logistic regression model, predicting hypoglycemia during the first 15 min was higher (98%), comparing to LSTM (88%). However, the LSTM model (87%) exceeded the accuracy of hypoglycemia prediction of the logistic regression (83%) during an hour prognosis. The same pattern observed in hyperglycemia - ARIMA model (60%, 1 hour), logistic regression (96%, 15 minutes) and LSTM (85%, 1 hour) Conclusions: These findings suggest that different models may have varying strengths and weaknesses in predicting glucose levels, and the choice of model should be carefully considered based on the specific requirements and context of the clinical application. The logistic regression model was more accurate for the next 15 minutes, especially predicting hypoglycemia. However, the LSTM model exceeded logistic regression for the next one hour prediction. Future research could explore hybrid models or ensemble approaches that combine the strengths of multiple models to further improve the accuracy and reliability of glucose predictions.

Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.

Accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated its effect on the number of macrophages and endothelial cells (ECs) within the CM. Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and Transglutaminase II, respectively. Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and 4-fold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p<0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals.

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of DNA-aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with AGE-Apt or control aptamer for 6 weeks and then sacrificed. Plasma glucose, testicular AGEs, and RAGE gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice; the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited the seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing the AGE–RAGE-induced oxidative stress and inflammation in the testes of DM mice.

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and one of the leading causes of blindness globally. Due to the progressive nature of the disease, earlier detection and timely treatment can lead to substantial reductions in the incidence of irreversible vision-loss. Artificial intelligence (AI) screening systems have offered clinically acceptable and quicker results in detecting diabetic retinopathy from retinal fundus and optical coherence tomography (OCT) images. Thus, this systematic review and meta-analysis of relevant investigations was performed to document the performance of AI screening systems that were applied to fundus and OCT images of patients from diverse geographic locations including North America, Europe, Africa, Asia, and Australia. A systematic literature search on Medline, Global Health, and PubMed was performed and studies published between October 2015 and January 2020 were included. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and AI-based investigations were mandatory for studies inclusion. The abstracts, titles, and full-texts of potentially eligible studies were screened against inclusion and exclusion criteria. Twenty-one studies were included in this systematic review; 18 met inclusion criteria for the meta-analysis. The pooled sensitivity of the evaluated AI screening systems in detecting diabetic retinopathy was 0.93 (95% CI: 0.92-0.94) and the specificity was 0.88 (95% CI: 0.86-0.89). The included studies detailed training and external validation datasets, criteria for diabetic retinopathy case ascertainment, imaging modalities, DR-grading scales, and compared AI results to those of human graders (e.g., ophthalmologists, retinal specialists, trained nurses, and other healthcare providers) as a reference standard. The findings of this study showed that the majority AI screening systems demonstrated clinically acceptable levels of sensitivity and specificity for detecting referable diabetic retinopathy from retinal fundus and OCT photographs. Further improvement depends on the continual development of novel algorithms with large and gradable sets of images for training and validation. If cost-effectiveness ratios can be optimized, AI can become a financially sustainable and clinically effective intervention that can be incorporated into the healthcare systems of low-to-middle income countries (LMICs) and geographically remote locations. Combining screening technologies with treatment interventions such as anti-VEGF therapy, acellular capillary laser treatment, and vitreoretinal surgery can lead to substantial reductions in the incidence of irreversible vision-loss due to proliferative diabetic retinopathy.

Diabetes becomes a life threatening non-communicable disease in the world, according to International Diabetic Federation (IDF) in 2023, an estimated 537 million adults (20-79 years) are living with diabetes, which is equivalent to 9.3% of the global adult population. This number is predicted to rise to 643 million by 2030 and 783 million by 2045. Over 3 in 4 adults with diabetes live in low- and middle-income countries. Diabetes is a persistent metabolic condition marked by increased levels of glucose in the bloodstream. It is a significant global health concern, affecting millions of individuals worldwide. It having the symptoms of drowsiness for the whole day if not properly examined or treated well. It is targeted to spread over the younger age community and the number is growing in the exponential fashion. Even day to day many advancements have come from the researcher to diagnose, to find solutions to prevent from newer entry. Authors have taken a dataset with 57 non diabetic and 20 diabetic patients with the total 28735 micro array gene to undergone pre-processing process and reduced up to 22960 gene data using Dimensionality Reduction (DR) such as Detrend Fluctuation Analysis (DFA), Chi square probability density function (Chi2PDF), Firefly algorithm Cuckoo search were used in this research. Meta heuristic algorithms like Particle swarm Optimization (PSO) and Harmonic Search (HS) are used for feature selection. Further seven classification techniques such as Non-Linear Regression (NLR), Linear Regression (LR), Logistics Regression (LoR), Gaussian Mixture Model (GMM), Bayesian Linear Discriminant Classifier (BLDC), Softmax Discriminant Classifier (SDC), Support Vector Machine – Radial Basis Function (SVM-RBF) are using to make a decision, predictive analysis and segregate the data according to the level of blood glucose as Diabetic Patient (DP) and Non-Diabetic Patient (NDP).

Chronic diseases such as childhood DM are a complex and continuous struggle as well as a great challenge both for the children who face the disease and for their parents. Type 1 DM is characterized by the complex management of the therapeutic treatment thus causing physical and psychological complications in family members. There are many families who, upon hearing the diagnosis of their child with DM, stand still in front of these new facts as their lives change. All these unprecedented conditions cause parents intense stress, discomfort and mental burden as the only thing that concerns them now is how the family will survive in the face of the current conditions they are experiencing as well as the future of the sick child. The purpose of this brief literature review is to present the research findings which are related to the quality of life among parents of children and adolescents with diabetes.

Diabetes mellitus, a metabolic disorder that is persistent in nature, is identified by an elevated concentration of glucose in the bloodstream. The disease has become a major public health problem, affecting millions of people globally, and is associated with significant morbidity and mortality. The increasing prevalence of diabetes and the lack of effective therapeutic interventions have led to the exploration of alternative and complementary forms of therapy, including ethnomedicine. Ethnomedicine is the study of traditional medical systems and the medicinal plants used by Indigenous communities. In other words, Ethnomedicine refers to the traditional medical practices and beliefs of a particular cultural or ethnic group. The most popular example of traditional medicine is the use of Aloe vera for the treatment of various diseases such as sunburn, cuts, burns, hypertension, diabetes, and jaundice for thousands of years [1]. In recent years, there has been increasing interest in the potential role of ethnomedicine in the management of diabetes, given its widespread use in many communities and its potential to offer cost-effective and culturally acceptable treatment options. It encompasses a range of traditional healing practices, including herbalism, acupuncture, and massage therapy. Despite the inconsistencies, there is growing evidence to suggest that certain ethnomedical practices may be effective in the management of diabetes [2,3]. For example, several studies have shown that certain herbal remedies, such as cinnamon, ginseng, and bitter melon, may have potential benefits in terms of improving glucose control and reducing the risk of complications associated with diabetes. Evidence-based ethnomedicine is an approach that applies scientific principles and methods to evaluate the efficacy and safety of traditional medical practices. This approach is crucial in the development of effective and safe ways to treat diabetes. To date, there have been numerous studies conducted to examine the efficacy and safety of various ethnomedical interventions for diabetes, including herbal remedies, dietary changes, and physical activity [4]. However, it is important to note that not all ethnomedical interventions for diabetes have been thoroughly evaluated, and many remain unproven. Furthermore, some interventions may be associated with significant risks, particularly in terms of drug interactions and adverse effects. As such, it is crucial that any ethnomedical interventions for diabetes be carefully evaluated using rigorous scientific methods and that patients be advised to consult with their healthcare provider before using any such interventions. It is important to note that the results of these studies have been mixed, with some showing promising results, while others have failed to demonstrate significant benefits. In this chapter, the evidence-based current state of ethnomedicine for diabetes was reviewed. We first provide an overview of diabetes and its pathophysiology, followed by a discussion of traditional medicinal practices used to treat the disease. We then present a systematic review of the scientific literature on the use of ethnomedicine for diabetes, focusing on herbal remedies and dietary interventions. Our review found that several medicinal plants offered promising results to treat all types of diabetes. For example, Gymnema sylvestre, a traditional Indian herb, has been shown to reduce blood glucose levels and improve insulin sensitivity [5]. Additionally, the use of bitter melon (Momordica charantia) has been shown to reduce fasting blood glucose levels and improve glucose tolerance in individuals with type 2 diabetes [6]. Another important aspect of ethnomedicine for diabetes is the use of dietary interventions [7]. Traditional diets, such as the Mediterranean diet, have been shown to have beneficial particularly in terms of improving glycaemic control, reducing the risk of cardiovascular disease, and insulin sensitivity [8]. Additionally, the use of low-carbohydrate diets, such as the ketogenic diet, has been shown to improve glycaemic control in individuals with type 2 diabetes [9]. Traditional medicine has a long history of treating the symptoms and managing the condition. However, the efficacy and safety of these traditional practices have not always been scientifically tested, and there is a lack of standardization and regulation in the production and use of traditional remedies for diabetes. This creates a challenge for healthcare providers and patients, who need to ensure that the treatments they use are safe and effective. Additionally, there is a need for further research to understand the mechanisms by which traditional remedies may be effective in managing diabetes and to determine the optimal dosage and administration methods [9]. Finally, it is also important to understand that the use of traditional remedies may interact with conventional medications, leading to adverse effects; for example, the use of Chinese traditional medicine, known as “herb ginseng,” for the treatment of various health conditions, including diabetes sometimes cause the side effect such as dizziness, confusion, and fainting while interacting with the anti-diabetic medications [10]. Therefore, it is important to approach the use of ethnomedicine for diabetes with caution and under the guidance of a qualified healthcare professional. In conclusion, evidence-based ethnomedicine offers a promising approach to the treatment of diabetes. While further research is needed to fully understand the mechanisms and safety of these interventions, the results to date suggest that traditional remedies and dietary interventions have the potential to be effective in the management of this disease. However, it is important to approach the use of ethnomedicine for diabetes with caution and under the guidance of a qualified healthcare professional and to continue to conduct rigorous scientific research to fully understand the benefits and risks associated with these interventions.

α-amylase inhibitors (aAIs) have been proved efficient for the management of type 2 diabetes. This study aimed to search the potential aAIs produced by microbial fermentation. Among various bacterial strains, Pseudomonas aeruginosa TUN03 was found as a potential aAI - producing strain, and shrimp heads powder (SHP) was screened as the most suitable C/N source for fermentation. P. aeruginosa TUN03 exhibited the highest aAIs productivity (3100 U/mL) in the medium containing 1.5% SHP with the initial pH of 7-7.5, and fermentation was performed at 27.5 °C in 2 days. Further, aAIs compounds were investigated for scale-up production in a 14 L – bioreactor system, and the results highlighted high yield (4200 U/mL) in much shorter fermentation time (12 h) compared to fermentation in flasks. The bioactivity-guided purification resulted in the isolation of one major target compound. This active compound was confirmed as hemi-pyocyanin (HPC), with good purity, via using high-performance liquid chromatography and gas chromatography-mass spectrometry. Notably, HPC demonstrated potent activity comparable to acarbose, a commercial antidiabetic drug; this is the first-ever report of aAI activity of HPC. The docking study indicated that HPC inhibits α-amylase via binding to amino acid Arg421 at the biding site on enzyme α-amylase with good binding energy (-9.3 kcal/mol) and creating two linkages of H-acceptor.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Objective To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure. Method We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant. Results Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. Conclusion The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologist, and neonatal pediatricians.

To Identify risk factors of perinatal complications amongst macrosomic babies in a reference hospital structure.We conducted a case-control institutional based study. Cases and controls of singleton livebirths were extracted from the maternity registry from January 2017 to December 2019 The case population consisted of mother and child macrosomic couples with perinatal complications. The control group consisted of couples without perinatal complications. Matching was done on age and sex. The main primary end point was the risk factors for complications. Data were analyzed using R, software version3.0 in adjusted and unadjusted analysis with p<0.05 threshold considered statistically significant.Out of 362 couples, we had 186 cases and 176 controls. Maternal age ≥30 years (p=0.024); non-screening for gestational diabetes (p=0.027); history of caesarean section (p=0.041); weight gain ≥16 kg (p<0.001); maternal HIV (p=0.047); birth weight ≥4500g (p=0.015) and birth height ≥ 52.7 ±1.7cm (p=0.026) were risk factors. The delivery of a macrosomic baby remains problematic in this setting. The improvement of the maternal-fetal prognosis requires quality prenatal surveillance and management by a multidisciplinary perinatal team involving obstetricians, endocrinologists and neonatal pediatricians.

World population is in a demographic transition, with an increase in number of older adults and prevalence of diseases related to aging. This study evaluated in vitro the potential of an ultrasound-assisted extract from Durvillaea incurvata to inhibit key enzymes associated with development of age-related diseases. Results show that an ultrasound-assisted extract as well as conventional extract from Durvillaea incurvata presented anti-diabetes potential by exhibiting inhibitory activity against α-glucosidase enzymes (91.8 ± 1.0 % and 93.8 ± 0.3 % respectively, at 500 µg/mL) and α-amylase (42.2 ± 1.4 % and 61.9 ± 0.9 % respectively, at 1500 µg/mL), related to starch digestion and postprandial glycemic response. Also, extracts presented inhibitory activity on the enzyme acetylcholinesterase (51.5% and 50.8% respectively, at 500 µg/mL) and butyrylcholinesterase (32.8% and 34.4% respectively, at 0.5 mg /mL), biomarkers associated with Alzheimer's disease, and showed inhibitory activity against angiotensin-I converting enzyme (98.7 ± 7.4% and 93.0 ± 3.4% respectively, at 2.0 mg /mL), key in the regulation of vascular tone and blood pressure, which helps to prevent the development of hypertension. In conclusion, the ultrasound-assisted extract of Durvillaea incurvata has the potential to prevent the development of age-related pathologies, such as diabetes, Alzheimer's disease, and hypertension.

Metabolic syndrome is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reduced risk of chronic disease. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for prevention or treatment of metabolic syndrome and associated health conditions. A search of PubMed and Scopus databases was carried out to assess the available clinical or cohort evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders or the health of individuals with metabolic syndrome or associated diseases were included. Out of a total of 1742 papers identified, there were 146 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, Nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric for blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of metabolic syndrome and associated disorders.

In a 24-week-long experiment, 31 rats were assigned to one of 3 groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. Both groups experienced significantly increased caloric intake but did not gain weight above the Control group level. Adipocytes in subcutaneous and visceral adipose depots of both groups had smaller size compared to control and higher density in tissue. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated that in both experimental groups high tissue respiration is associated with better biochemical profile and closer to control adipose tissue morphology. Increased tissue respiration in adipose depots could be an important mechanism of resilience to excessive caloric intake.

Covid-19 pandemic has greatly affected the whole world since the beginning and it continues to affect it. The main aim of this study is to show how Covid-19 affect other mortal diseases; cancer, heart diseases, and diabetes in near future. With this purpose two mathematical models are proposed via Ordinary Differential Equations (ODEs); one for the relationship between Covid-19 and cancer and one for the relationship between Covid-19, diabetes and heart diseases. Afterwards, stability analyses of these models are demonstrated. In order to see the effect of parameters on the disease compartments, sensitivity analysis is applied. Results of sensitivity analysis revealed that huge percentage of people are still scared of visiting doctors and this may lead a massive increase in the diagnosis of other diseases for upcoming years. Moreover, figures displayed that there exists a relationship between diabetes and heart diseases. Especially, diabetes patients should be careful about their health situations and take care of their heart. In order to provide these, awareness of people should be developed.

Objectives and Background: Gestational diabetes (GDM) is a common pregnancy complication, defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1-hour 50g oGCT (oral glucose challenge test) followed by a 2-hour 75g oGTT if the first was pathological. This analysis examines the correlation of 75g oGTT glucose levels and fetomaternal outcome. Methods: Data of 1664 patients from a gestational diabetes consultation clinic at the Charité University hospital in Berlin, Germany, were analyzed retrospectively from 2015 until 2022. The 75g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1-hour and 2-hour values after glucose application. These subtypes were compared regarding baseline characteristics as well as fetal and maternal outcome. Results: GDM-IFH and GDM-CH women displayed higher preconceptional BMI and required insulin therapy more frequently (p<0,001). The GDM-IFH group was at higher risk of having a primary cesarean section (p=0,047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p=0,013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p<0,001) and birth weight percentiles (p<0,001) and were at increased risk of being large for gestational age (LGA) (p=0,004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p=0,027) or with low fetal weight <30th percentile (p=0,003). Conclusion: This analysis shows a strong association between glucose response pattern in the 75g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach in prenatal care after a GDM diagnosis.

Diabetes is one of the fatal diseases that play a vital role in the growth of other diseases in the human body. Controlling and curing diabetes in its early stages is the most significant technique to avoid its effects of diabetes. However, lack of awareness and expensive clinical tests are the primary reasons to skip clinical diagnosis and take preventive methods in lower-income countries like Bangladesh, Pakistan, and India. From this perspective, the study aims to build an automated machine learning (ML) model, which will predict diabetes at an early stage using socio-demographic characteristics rather than clinical attributes. Because clinical features are not always known to all people from lower-income countries. To find the best fit supervised ML classifier of the model, we applied six classification algorithms and found that RF outperformed with an accuracy of 99.36%. In addition, the most significant risk factors were found based on the SHAP value by all the applied classifiers. The study reveals that polyuria, polydipsia, and delayed healing are the most significant risk factors for growing diabetes. The findings indicate that the proposed model is highly capable of predicting diabetes in the early stages.

Worldwide epidemiological data indicates insufficient diagnosis of diabetes as an increasing problem of public health. Searching for solutions in this disadvantageous situation, occupational medicine health services seem to open up a unique opportunity to recognize some abnormalities in early steps, especially among the asymptomatic working-age population. 316 workers underwent obligatory prophylactic examinations. In patients with twice assayed FGL ≥ 126 mg/dl (7.0 mmol/l) the additional intervention was implemented, including further diagnostic process and therapy in General Practice (GP), followed by examination by an occupational health specialist within 3 months. The diagnosis of previously unknown diabetes was established among 2.5% of examined workers. All patients referred to the GP due to detected glycaemia impairment visited their doctor and finished the diagnostic process, took up therapy constrained by the occupational health physician to show the effects of intervention within 3 months. Prophylactic medical check-ups allow improved compliance and medical surveillance over glycaemia impairment in patients with prediabetes states, unknown diabetes or uncontrolled clinical course of diabetes. Considering fasting glucose level during mandatory prophylactic examination helps effective prevention of diabetes and its complications and thus give public health system benefits.

DKA represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, T2DM in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, DKA and hyperosmolar hyperglycaemic state (HHS), or between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration and restoration of shifting electrolyte disorders and underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, an-tagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including inter-section points to the new generation of antidiabetic drugs. We provide insight into the effective-ness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Background: Myocardial infarction (MI) is a major cause of mortality worldwide. Its presentation as ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) is influence by atherosclerosis risk factors. Aim: To assess the patterns of presentation and predicting risk factors of acute MI in Kosovo. Methods: This is a cross sectional study from the Clinic of Cardiology of the University Clinical Center of Kosovo, which included all patients hospitalized with acute MI over a period of 7 years (January 1st, 2014 to December 31st, 2020). Data was collected using a structured questionnaire and epidemiological patterns and risk factors were analyzed. Results: Among 7353 patients admitted with acute MI (age 63 ± 12 years, 29% female), 4366 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. Patients age was not different between the two groups (p=0.077). NSTEMI patients smoked less (48.3% vs. 54%, p<0.001), but were more diabetics (37.8% vs. 33.6%, p<0.001), more hypertensives (69.6% vs. 63%, p<0.001), frequently had family history for coronary artery disease (CAD) (40% vs 38%, p=0.009), and included more females compared to STEMI patients (32% vs 27%, p<0.001). The two groups of patients, did not differ in the prevalence of significant CAD on angiography (66.8% vs. 67.8%, p = 0.396), but NSTEMI patients underwent less primary percutaneous interventions compared with STEMI patients (43.6% vs. 55.2%, p < 0.001). Conclusion: In Kosovo, STEMI is commoner than NSTEMI, who were mostly males, more likely to have diabetes, hypertension and family history for CAD compared to those with NSTEMI. Smoking and arterial hypertension proved the strongest predictors of acute MI, in Kosovo, thus highlighting the urgent need for better atherosclerosis risk control and education strategy.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

This review summarizes available data on invasive procedures applied with questionable indications in Russia in the recent past: mastectomy with the removal of muscles, gastrectomy for peptic ulcers, spleno-renal anastomosis for diabetes mellitus, thoracic surgery for bronchial asthma, overuse of surgery in tuberculosis, excessive and compulsory treatments of alcohol-dependent patients, etc. Among factors contributing to the use of invasive procedures with unproven efficiency have been the partial isolation from international scientific community, insufficient consideration of the principles of professional autonomy, informed consent and scientific polemics, training of medical personnel. It is known that invasive procedures can exert a placebo effect, which might have contributed to reported efficiency of some methods discussed here. However, by definition, placebo must be free of risks.

This study investigates the metabolic parallels between stimulated pancreatic beta cells and cancer cells, emphasizing glucose and glutamine metabolism. Addressing the significant public health challenges of Type 2 Diabetes Mellitus (T2DM) and cancer, we aim to deepen understanding of the mechanisms driving insulin secretion and cellular proliferation. Our analysis of anaplerotic cycles and NADPH's role in biosynthesis elucidates their vital functions in both processes. Additionally, we find that both cell types share an antioxidative response mediated by the Nrf2 signaling pathway, glutathione synthesis, and UCP2 upregulation. Notably, UCP2 facilitates the transfer of C4 metabolites, enhancing reductive TCA cycle metabolism. We also uncover that hypoxic responses are transient in beta cells post-stimulation but persistent in cancer cells. By synthesizing these insights, our research suggests novel therapeutic targets for T2DM, highlighting the shared metabolic strategies of stimulated beta cells and cancer cells. This comparative analysis not only illuminates the metabolic complexity of these conditions but also emphasizes the crucial role of metabolic pathways in cell function and survival, offering fresh perspectives for tackling T2DM and cancer challenges.

Individuals with metabolic syndrome have increased risk for developing health conditions, in-cluding cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary pat-terns and habits are extremely successful in controlling more than one of the metabolic syn-drome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardi-ovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

This scoping review comprehensively explores the existing literature on fenugreek (Trigonella foenum-graecum), a versatile herb known for its culinary and traditional medicinal uses. The review focuses on two key aspects: the hypoglycemic mechanism of fenugreek and its impact on milk production in breastfeeding women. By systematically analyzing and synthesizing the available evidence, this review aims to enhance our understanding of fenugreek's potential applications and identify research gaps for future systematic reviews. The search strategy targeted English-language animal studies published within the last five years that specifically investigated fenugreek's hypoglycemic mechanism and its effects on milk production. A total of 15,236 articles were initially identified from databases such as PubMed, Sci finder and ScienceDirect. After a rigorous selection process, including thorough evaluation of titles, abstracts, and full-texts, a subset of articles (including those titled "Impact of Fenugreek on Milk Production in Rodent Models of Lactation Challenge" and "Fenugreek Stimulates the Expression of Genes Involved in Milk Synthesis and Milk Flow through Modulation of Insulin/GH/IGF-1 Axis and Oxytocin Secretion") were included for detailed analysis. The findings 18 articles from the included studies demonstrate promising results regarding fenugreek's potential to stimulate milk production and regulate blood glucose levels. However, further research is necessary to unravel the underlying molecular pathways, establish optimal dosage guidelines, and assess long-term side effects. Overall, this scoping review offers valuable insights for lactating women seeking to enhance milk production and individuals managing blood sugar levels, providing potential alternative approaches for supporting lactation and glycemic control.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

In this review, we discuss the insulin resistance (IR) and its development in the insulin target tissues that leads to diabetes. Also, we highlight the use of induced pluripotent stem cells (iPSCs) to understand the mechanisms underlying the development of IR. IR is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Although there are currently several mouse models for both IR and T2D that had provided a lot of information about the disease, these models cannot recapitulate all the aspects of this complex disease as seen in each individual. Patient-specific iPSCs can overcome the hurdles faced with the classical mouse models for studying IR. iPSC technology can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of the genome editing and iPSCs may provide important information about the inherited factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

The number of people with gluten-related illnesses has been increasing and the available treatments include the introduction of a gluten-free diet. In the bakery industry, there are problems with gluten-free products, namely the important characteristics that this component gives to doughs and the low nutritional value they present. A disease that has also increased in recent years is diabetes mellitus, which is characterized by a lack of insulin and the effectiveness of its action (type 1 diabetes) or tissue insensitivity to the hormone (type 2 diabetes). In terms of treatments, there are several approaches: inhibition of digestive enzymes (α-amylase and α-glucosidase) or techniques based on mechanisms of action (stimulation of insulin production and release, insulin transport and decreased glucose absorption). Hyperglycemia is also associated with the production of reactive oxygen species, which leads to cell apoptosis. On the other hand, there was also an association with high levels of cholesterol in the body, which contributed to the development of other types of diseases. In this sense, macroalgae have been studied as a source of natural compounds and used as food supplements, due to their protein, amino acid and mineral content, and the anti-diabetic effect in controlling the glycemic index, oxidative stress and cholesterol have already been demonstrated. Seaweed emerges as a promising source of bioactive nutraceuticals for individuals with coeliac disease, diabetes, and hyperglycemia. The rising prevalence of gluten-related illnesses calls for effective treatments, and seaweed's potential in enhancing the nutritional value of gluten-free products is noteworthy. Additionally, its demonstrated anti-diabetic effects, including glycemic index control, oxidative stress reduction, and cholesterol management, make it a valuable dietary supplement. Further research is needed to explore the specific bioactivities of seaweed compounds and their mechanisms of action. Integrating seaweed-based nutraceuticals into diets could complement traditional treatments, offering potential health benefits to those with coeliac disease and diabetes.

Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with the pathogenesis of hypertension, but so far, the mechanism has not been well defined. We hypothesize that exposure to Cd causes a decline in the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73m2 (low eGFR). The mean blood Cd and mean urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Prevalence odds ratio (POR) for hypertension rose twofold in those with a medium Cd burden and blood Cd levels of 0.61-1.69 µg/L. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in those with hypertension was 7.5 mL/min/1.73m2 lower than those who were normotensive with the same Cd body burden. In addition, higher systolic blood pressure (SBP) values were associated with older age (β = 0.243), higher BMI (β = 0.113), lower eGFR (β = −0.106) and diabetes (β = 0.216). Mean SBP in those who had low eGFR and medium and heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. Thus, chronic environmental exposure to Cd that produces urinary and blood Cd levels of 0.57-0.61 µg/L, increases the risk of hypertension, and this could be mediated by a declining GFR.

The fetal splenic artery pulsatility index (PI) is a parameter that reflects fetal well-being and has been used as a predictor of adverse pregnancy outcomes. The aim of this study was to investigate the predictive value of splenic artery PI in GDM class A1 cases for NICU admission. In this prospective case controlled study, only sixty single pregnancy cases diagnosed with gestational diabetes mellitus class A1 were evaluated. Fetal splenic artery Doppler parameters Peak systolic velocity (PSV), Pulsatility index (PI), Resistivity index (RI) and End diastolic velocity (EDV) were measured in all cases. The rate of re-quirement of need of neanoatal intensive care unit was noted. In cases with need fetal intensive care, fetal splenic PI index was found to be statistically significantly lower than in healthy cases without it (0.94 ± 0.29 vs. 1.70 ± 0.53, respectively, p

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

Background: Despite advances in diabetes-related treatments, the effects of the disease have not yet been adequately reversed or prevented in patients. Therefore, there is an urgent need to develop more effective medication-assisted treatments in this field. Methods: In this study, type 1 diabetes mice models was established using multiple low-dose alloxan, and the diabetic mice were treated with three doses of dimethyl fumarate (DMF) i.e low, medium, and high viz. 20, 40 and 80 mg/kg, respectively for a period of 21 days. Then, specific test were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression, and histopathological changes in the mice kidney and liver. Results: The obtained results showed remarkably improved anti-diabetic, hepato-renal-protective, and oxidative stress indexes of DMF in alloxan-induced diabetic mice (p< 0.001). Treated mice with DMF demonstrated a noteworthy decrease in blood glucose levels when compared with diabetic group (p< 0.001). Diabetic liver and kidney tissues showed marked dilation of bile ducts, tubules, infiltration, and inflammation. On the contrary, the histological features of the treated mice with DMF improve as shown by normal size of glomerular capillaries along with decrease in less dilatation of ducts in comparison with diabetic mice. The real-time quantitative PCR results indicated that DMF injection decreased the alloxan-induced increase of significant elevations in mRNA levels of pro-inflammatory cytokines and adhesion molecules such as TNF-α, IL-6, and NF-κB levels in both kidney and liver tissues. Meanwhile, mice treated with DMF showed an increase in Sirt1 and Nrf2 expression in comparison to diabetic group. Conclusion: In conclusion, it can be concluded that DMF treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating ROS inflammatory pathways. Keywords: Diabetes, Dimethyl fumarate, Alloxan, Anti-inflammatory responses, Hepato-renal-protective effects.

Bisphenols are widely used in the synthesis of polycarbonate plastics, epoxy resins and thermal paper, which are used in manufacturing items of daily use. Packaged foods and drinks are the main sources of exposure to bisphenols. These chemicals affect humans and animals by disrupting the estrogen, androgen, progesterone, thyroid, and aryl hydrocarbon receptor functions. Bisphenols exert numerous harmful effects because of their interaction with receptors, ROS formation, lipid peroxidation, mitochondrial dysfunction, and cell signal alterations. Both cohort and case-control studies have determined an association between bisphenol exposure and increased risk of cardiovascular diseases, neurological disorders, reproductive abnormalities, obesity, and diabetes. Prenatal exposure to bisphenol results in developmental disorders in animals. These chemicals also affect the immune cells and play a significant role in initiating the inflammatory response. Exposure to bisphenols exhibit age, gender, and dose-dependent effects. Even at low concentrations, bisphenols exert toxicity, and hence deserve a critical assessment for their uses. Since bisphenols have a global influence on human health, the need to discover the underlying pathways involved in all disease conditions is essential. Furthermore, it is important to promote the use of alternatives for bisphenols, thereby restricting their uses.

Diabetes mellitus is the fifth deadliest disease in the developing countries. Even with all the research and new drugs available, combating diabetes is still challenging. There are successes in finding new cost effective drugs without side effects, even if not perfect. In our investigation we studied binding mechanism of secondary metabolite of T. chebula in silico. It was observed that three compounds out of 16 have a higher binding affinity for the target proteins. Ellagic acid showed highest binding affinity with alpha amylase, beta glucosidase and alpha glucosidase with lesser binding energies -4.5kcal/mol, -5.36kcal/mol and -4.48kcal/mol respectively. Arjungenin has lesser binding energy of 4.77 kcal/mol with glucokinase while luteoline has binding energy of -7.25kcal/mol for enzyme glycogen synthase kinase. These entire compounds interacted with non-covalent interaction. Petroleum ether extract showed the significant alpha amylase inhibitory activity i.e. 51.22% as compared to standard drug (65.99%).TLC analysis revealed the presence of total 9 compounds in different plant extracts one of them might be a lead compound which could be further exploited for the development of novel safer and potent antidiabetic drug.

Mucormycosis is an opportunistic fungal infection that is increasingly affecting patients with Coronavirus Disease (COVID-19). This connection is particularly pronounced in specific populations, including individuals with diabetes or those who have recently undergone corticosteroid therapy. Additionally, Cytomegalovirus (CMV) infection is a frequent complication among COVID-19 patients who have previously received corticosteroid or other immune-modulatory treatments. In this case report, we present the clinical details of a 56-year-old male who developed post-COVID pneumonia complicated by both cutaneous mucormycosis and CMV infection.

Objective: This study examined the impact of Japan’s state of emergency on trends in diabetes care during the coronavirus disease 2019 (COVID-19) pandemic. Design: A descriptive and retrospective study. Setting: Showa University Hospital, Japan. Participants: Patients with diabetes who received medical treatment from 2018 to 2020. Determinants of interest: Number of patients with diabetes visiting the hospital per week. To examine the impact of the Japan’s state of emergency, the number hospital visiting by patients with diabetes was summarized from 28 weeks of data, from calendar week 8 to week 35, for each year. Results: Compared with the mean of 2018 and 2019, no significant difference was found between the three periods (before, during, and after the state of emergency). However, the numbers of patients from both inside and outside Tokyo increased at 7 weeks after the state of emergency was lifted. Conclusions: A significant increase in the numbers of patients with diabetes was seen compared with the same period in 2018 and 2019, suggesting that the state of emergency may have hindered diabetes care. Therefore, patients with diabetes should be followed up continuous of diabetes care while keeping a close eye on measures.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis presents a critical synthesis of development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus, qualitatively synthesized. Out of these, 47 were included into quantitative synthesis. There was substantial heterogeneity in reporting of these outcomes (I²= 88.35%, Q= 317.64), with significant improvement (SMD=0.36, 95% CI: 0.23 to 0.49) noted in biomedical outcomes in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (P < 0.001). These interventions should be implemented in healthcare and community settings to improve health of patients suffering from DM and obesity.

Erectile dysfunction (ED) is the inability to achieve or maintain an erection during sexual performance. ED is one of the most common and neglected complications of diabetes. Almost 35-75% of diabetic men around the world suffer from ED. Although the exact mechanism by which diabetes causes ED is not well understood. However, several studies suggested it may be related to damage to the nerve and vessels that supply the penis.

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

Background. Human Milk (HM) is a dynamic nourishment: its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important evaluate the impact that gestational diseases have on HM components and if their presence, as source of oxidative stress in the mother, influence milk’s redox homeostasis. To assess Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) effect on milk’s total oxidative load, we chose to investigate both oxidative and antioxidant aspects, with respectively Lipid hydrop-eroxides (LOOHs) and Glutathione (GSH)). Methods. GSH and LOOHs were quantified using an ELISA test. To investigate the effect of pathology on redox homeostasis, mixed linear model with unistructural covariance structure was performed. Results. A total of 120 mothers were re-cruited. The GSH concentration results significant lower in GDM women than in healthy only in colostrum (p<0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. Discussion. Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the anti-oxidant composition of HM mainly in colostrum, but in case of PE, the composition of HM milk is preserved.

Background/Aim: microRNAs (miRNAs) are key regulators of both physiological and pathophysiological mechanisms in diabetes and gastrointestinal (GI) dysmotility. Our previous studies have demonstrated the therapeutic potential of miR-10a-5p mimic and miR-10b-5p mimic (miR-10a/b mimics) in rescuing diabetes and GI dysmotility in murine models of diabetes. In this study, we elucidated the safety profile of a long-term treatment with miR-10a/b mimics in diabetic mice. Methods: Male C57BL6 mice were fed a high-fat, high-sucrose diet (HFHSD) to induce diabetes and treated by five subcutaneous injections of miR-10a/b mimics for a 5-month period. We examined the long-term effect of the miRNA mimics on diabetes and GI dysmotility, including an assessment of cancer risk as well as liver and colon inflammation using cancer and inflammatory biomarkers. Results: HFHSD-induced diabetic mice subcutaneously injected with miR-10a/b mimics monthly for 5 months exhibited a marked reduction in fasting blood glucose levels with restoration of insulin and significant weight loss, improved glucose and insulin intolerance, and restored GI transit time. In addition, the miR-10a/b mimic treated diabetic mice showed no indication of risk for cancer development and inflammation induction in the liver, colon, and blood for the 5 months post injections. Conclusion: This longitudinal study demonstrates that miR-10a/b mimics, when subcutaneously administered in diabetic mice, effectively alleviate diabetes and GI dysmotility for 5 months with no discernible risk for cancer or inflammation in the liver and colon. The sustained efficacy and favorable safety profiles position miR-10a/b mimics as promising candidates in miRNA-based therapeutics for diabetes and GI dysmotility.

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

myfood24 is a comprehensive self-completed online 24-hour dietary recall tool currently used for nutritional assessments in epidemiological research. However, its clinical application has been unexplored. This mixed methods prospective observational study explores the acceptability and usability of myfood24 in a clinical population, women with gestational diabetes (GDM). Women were recruited at their first diabetes antenatal clinic appointment. To assess acceptability and usability, they were asked to complete five 24-hour dietary recalls using myfood24 over two weeks and a user experience questionnaire; with a subset invited to participate in a one-to-one semi-structured interview. Of the 199 participants, mean maternal age was 33 years, mean booking BMI 29.7kg/m2, 36% primiparous, 57% White, 33% Asian. Of these 121 (61%) completed myfood24 at least once and 73 (37%) completed the user questionnaire; 15 were interviewed. Usability of myfood24 was measured using the System Usability Scale (SUS) and found to be good (mean 70.9, 95%CI 67.1, 74.6). Interviews identified several areas for improvement, including optimising its use for mobile devices. myfood24 appears to be acceptable and have potential to support self-management and behaviour change for women with GDM but requires adaptation to record blood glucose results alongside real-time tracking of diet.

Over the last decade, Psidium guajava L. (guava) leaves have demonstrated their in vitro and in vivo effect against Diabetes mellitus (DM). However, there is a lack of literature concerning the effect of the individual phenolic compounds present in the leaves in DM disease. For this reason, the aim of the present work was the in silico evaluation of each phenolic compound. The identification of an 80% ethanol extract of guava leaves revealed the presence of 73 compounds. The in silico study carried out with the DIA-DB web server revealed that aldose reductase was the target protein with heterogeneous affinity. Naringenin exhibited the highest number of interactions with target proteins, and compounds like catechin, quercetin, naringenin and morin displayed similarities with known antidiabetic drugs. In conclusion, the computational workflow showed that guava leaves contain several compounds that can play a therapeutic role in the treatment of DM.

Abstract: Diabetes mellitus (DM) is associated with severe COVID-19 infection and complications. This study assessed COVID-19 vaccine acceptance and hesitancy in diabetes and explored reasons for nonvaccinating. This was a web-based cross-sectional survey using a mixed-method approach conducted between March-May 2021 corresponding to most SSA countries' early vaccine rollout period. Participants were those aged ≥18 years with self-reported DM in 11 Sub-Saharan African (SSA) countries. Responses to comments on reasons for vaccine hesitancy and facilitators for vaccine uptake were analyzed. Of the 73 participants with DM, 65.8% were males older than 35 years (86.3%), had post-secondary education (90%), and a significant proportion was from South Africa (39.7%), Nigeria (28.8%) and Ghana (13.7%). 64.4% had COVID-19 symptoms, 46.6% were tested for COVID-19, of which 19.2% tested positive. Few participants (6.8%) had taken the COVID-19 vaccination, 65.8% were willing to take the vaccine, while 26.0% either refused or hesitated to take the vaccine. The main reasons identified for not taking the vaccine were: advice from religious leaders, concerns about the vaccine safety, its effects, and efficacy, mistrust of the pharmaceutical companies, the conspiracy theories around the vaccines, the process of production, and the personal belief of the participants. However, participants stated they would take the vaccine if given more education about it, receive positive feedback from those vaccinated, are rewarded for taking the vaccine or if vaccination becomes a condition for travel and employment. The findings of this study showed that uptake of the COVID-19 vaccine was very low in this high-risk group. It is imperative that efforts to increase the uptake of vaccines, such as the provision of education and relevant information, are made.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Background and objectives: Induction of labor (IOL) is an event that occurs in up to one-quarter of pregnancies; less is known about the outcomes and safety of IOL in obese pregnant woman; no data is available on misoprostol vaginal insert (MVI) IOL in high-risk pregnancy obese women. Objectives: (1) to evaluate the rate of successful IOL with 200 μg MVI in obese (Body Mass Index - BMI over 30 kg/m2) high-risk pregnant women: late-term pregnancy, hypertension or diabetes, compared to obese non-high-risk ones; (2) to evaluate the safety profile of MVI in high-risk pregnancy obese patients. Study design: We conducted a cross-sectional study in "Filantropia" Clinical Hospital, Bucharest, Romania, from June 2017 to September 2019 (28 months). From a total of 11,096 registered live births, IOL was performed in 206 obese patients; 74 obese high-risk pregnant patients matched the inclusion criteria; of these, 33.8% pregnancies (n=25) were late-term (41 – 41+6 weeks), 43.2% (n=32) had associated pathologies (hypertension and diabetes); labor induction was guided using a standardized protocol. We evaluated the maternal and gestational age, parity, fetal tachysystole, hyper-stimulation, initial cervical status, time from induction to delivery, drug side effects, mode of delivery, and neonatal outcomes. Results: (a) The overall successful labor induction rate, evaluated by the vaginal delivery rate, was 71.6% (n=53), spontaneously or instrumentally assisted; 28.4% (n=21) births were unsuccessful MVI IOL, converted into caesareans. (b) No significant differences were found regarding the maternal outcomes; in terms of perinatal outcomes of safety, four cases of high-risk pregnancies vaginally delivered were associated with neonatal intensive care unit (NICU) admissions and a one-minute Apgar score under seven (5.4%). Most cases with adverse effects of misoprostol have been managed conservatively, except for three emergency C-section cases. Conclusions: Misoprostol vaginal insert is a safe choice in IOL in obese high-risk pregnancies with good maternal and perinatal outcomes.

Pancreatic ductal adenocarcinoma (PDAC) a highly malignant neoplasm, is classified as one of the most severe and devastating types of cancer. PDAC is a notable malignancy that exhibits a discouraging prognosis and a rising occurrence. The interplay between diabetes and pancreatic cancer exhibits a reciprocal causation. The identified metabolic disorder has been observed to possess noteworthy consequences on health outcomes, resulting in elevated rates of morbidity. The principal mechanisms involve the suppression of the immune system, the activation of pancreatic stellate cells (PSCs), and the onset of systemic metabolic disease caused by dysfunction of the islets. From this point forward, it is important to recognize that pancreatic cancer-related diabetes (PCRD) has the ability to increase the likelihood of developing pancreatic cancer. This highlights the complex relationship that exists between these two physiological states. Therefore, we investigate into the complex domain of PSCs, elucidating their intricate signaling pathways and the profound influence of chemokines on their behavior and final outcome. In order to surmount the obstacle of drug resistance and eliminate PDAC, researchers have undertaken extensive efforts to explore and cultivate novel natural compounds of the next generation. Additional investigation is necessary in order to comprehensively comprehend the effect of PCRD-mediated apoptosis on the progression and onset of PDAC through the utilization of natural compound. This study aims to examine the potential anticancer properties of natural compound in individuals with diabetes who are undergoing chemotherapy, targeted therapy, or immunotherapy. It is anticipated that these compounds will exhibit increased potency and possess enhanced pharmacological benefits. According to our research findings, it is indicated that naturally derived chemical compounds hold potential in the development of PDAC therapies that are both safe and efficacious.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked with defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of altered mitochondrial dynamics in pancreatic β cells using ge-netic/pharmacologic approaches, and how these affect insulin secretion.

This study develops a 7-layer Long Short-Term Memory (LSTM) model to enhance early diabetes detection in Oman, aligning with the theme of 'Artificial Intelligence in Healthcare'. The model focuses on addressing the increasing prevalence of Type 2 diabetes, projected to impact 23.8% of Oman's population by 2050. It employs LSTM neural networks to manage factors contributing to this rise, including obesity and genetic predispositions, and aims to bridge the gap in public health awareness and prevention. The model's performance is evaluated through various metrics. It achieves an accuracy of 99.40%, specificity and sensitivity of 100% for positive cases, a recall of 99.34% for negative cases, an F1 score of 96.24%, and an AUC score of 94.51%. These metrics indicate the model's capability in diabetes detection. The implementation of this LSTM model in Oman's healthcare system is proposed to enhance early detection and prevention of diabetes. This approach reflects an application of AI in addressing a significant health concern, with potential implications for similar healthcare challenges globally.st diagnostic capabilities, representing a significant leap forward in healthcare technology in Oman.

Hospital readmission and length of stay prediction provide info to manage hospitals’ bed capacity and the number of required staff, especially during pandemics. We present a hybrid deep model called Genetic Algorithm-Optimized Convolutional Neural Network (GAOCNN) with a unique preprocessing method to predict hospital readmission and the length of stay in patients having various conditions. GAOCNN uses one-dimensional convolutional layers to predict hospital readmission and length of stay. The parameters of the layers are optimized using a genetic algorithm. To show the performance of the proposed model in patients with various conditions, we evaluate the model under three healthcare datasets; the Diabetes 130-US hospitals dataset, the COVID-19 dataset, and the MIMIC-III dataset. The diabetes 130-US hospitals dataset has information on both readmission and the length of stay, while COVID-19 and MIMIC-III datasets just include information on the length of stay. Experimental results show that the proposed model’s accuracy for hospital readmission is 97.2% for diabetic patients. Also, the accuracy of the length of stay prediction is 89%, 99.4%, and 94.1% for diabetic, COVID-19, and ICU patients, respectively. These results confirm the superiority of the proposed model compared to existing methods. Our findings offer a platform for managing healthcare funds and resources for patients with various diseases.

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p&lt;0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P&lt;0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

Disease-related data and information collected by physicians, patients, and researchers seem insignificant at first glance. Still, the same unorganized data contain valuable information that is often hidden. The task of data mining techniques is to extract patterns to classify the data accurately. One of the various Data mining and its methods have been used often to diagnose various diseases. In this study, a machine learning (ML) technique based on distributed computing in the Apache Spark computing space is used to diagnose diabetics or hidden pattern of the illness to detect the disease using a large dataset in real-time. Implementation results of three ML techniques of Decision Tree (DT) technique or Random Forest (RF) or Support Vector Machine (SVM) in the Apache Spark computing environment using the Scala programming language and WEKA show that RF is more efficient and faster to diagnose diabetes in big data.

Background. There is limited evidence on the relationship between chronic kidney disease (CKD) and frailty in older people in Vietnam. This study aimed to examine the prevalence of frailty and its impact on mortality in older patients with end-stage renal disease. Method. This is a prospective, observational study at two large Dialysis Centres in Vietnam from November 2020 to June 2021. Consecutive older patients diagnosed with end-stage renal disease and on dialysis were recruited. Participants’ frailty status was defined by the Clinical Frailty Scale (CFS). The study outcome was all-cause mortality at 6th month. Results. A total of 175 participants were recruited (mean age 72.4 years, 58.9% female). Using the cut-point of CFS ≥4, 87.4% of the participants were frail. Mortality at 6th month was 14.9%, 31.9% in participants with CFS ≥7, 12.8% in participants with CFS=6, 7.5% in participants with CFS from 4 to 5, and 4.5% in participants with CFS ≤3 (p=0.001). Cox regression analysis showed that compared to the non-frail participants, the probability of death over 6 months was nearly 2-fold higher in the mildly frail, 3-fold higher in the moderately frail, and 9-fold higher in the severely frail participants. Conclusion. This study demonstrated a very high prevalence of frailty in older patients with end-stage renal disease and dialysis and the significant impact of frailty severity on mortality. Healthcare providers should consider incorporating frailty screening into routine care for older patients with end-stage renal disease and dialysis.

Recurrent hypoglycaemia, a common side-effect of insulin therapy in the treatment of type 1 diabetes, induces impaired glucose-sensing. Better understanding of how astrocytes, important non-neuronal cells in the brain, function in low glucose environments may improve our understanding of recurrent hypoglycaemia-induced defective counterregulation. Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglcyaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca2+ levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca2+ responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that attenuates RLG-induced mitochondrial adaptations.

Curcuma longa is only a rich source of curcumin (1) and its major analogues demethoxycurcumin (2) and bisdemethoxycurcumin (3) among the Curcuma species. The content ratio of these three curcumins in turmeric is depended on the varieties and growing environment. Recently, curcumin (1) has been reported as potential inhibitor of hepatic and enzymatic protein tyrosine phosphatase 1B (PTP1B) and its related disorders such as hypertriglyceridemia, hyperlipidemia and liver steatosis. Thus, we further purified curcumins (1–3) from C. longa and investigated their inhibitory effects against PTP1B and α-glucosidase enzymes. As the result, curcumins (1–3) exhibited potential PTP1B inhibition with IC50 values of 37.8 ± 1.4, 45.3 ± 0.7, and 72.6 ± 1.1 μM, respectively, and α-glucosidase inhibition with similar manner (IC50 values of 78.2 ± 0.2, 82.4 ± 0.6, and 90.6 ± 1.0 μM, respectively). These results reveal a key role of methoxylation in the variation of PTP1B and α-glucosidase inhibitory activity for these curcumins. In addition, density functional theory (DFT) was used accompanying with molecular docking (MD) to analyze the ligand stability and the interaction of curcumins (1–3) with PTP1B and glucoside hydrolase proteins. Assay-based results and the MD data obtained are highly correlation suggesting that the deterioration of the enzyme activity caused by the distortion of structural conformation of PTP1B and glucoside hydrolase may be related to the arrangement of amino acids in protein structure. This reported for the first time that inhibitory effects of curcumins (1–3) against PTP1B and glucoside hydrolase have been examined in vitro and in silico as well.

Pregnancy is a dynamic state with multiple metabolic changes occurring including insulin resistance. Gestational diabetes mellitus (GDM), a form of diabetes that appears during pregnancy, develops if metabolic aberrations occur, in particular, in normal pregnancy-induced insulin resistance. Multi-omics is a powerful approach for uncovering the mechanisms driving metabolic change in different physiologic and pathologic states. A recent study demonstrated that the gestational gut microbiome mediates pregnancy metabolic adaptations through effects on gut indoleamine-2,3 dioxygenase 1 activity and the production of kynurenine. Using the dataset generated from this highly controlled study, we performed a comprehensive analysis of the pregnancy-specific physiological and metabolic profiles, 16S rRNA microbiome, and plasma untargeted LC-MS metabolome data. To facilitate the utilization of these analysis results by other researchers, we developed MOMMI-MP, a database that provides an easy-to-use platform to browse and search differential abundant microbial taxa and metabolites, and to examine metabolic pathways. The datasets consist of data collected from 3 genetically diverse strains of mice (C57BL/6J, CD1, and NIH-Swiss) over 6 time points during the gestational (days 0, 10, 15, and 19 during gestation) and postpartum (days 3 and 20 after delivery) states, totaling 180 samples for each strain. The computational results are presented in various tables and plots, and organized in MOMMI-MP to empower exploratory analyses by other researchers. In conclusion, MOMMI-MP is a resource to facilitate the investigation of novel mechanisms governing metabolic changes during pregnancy.

Culinary herbs and spices are widely used in daily diets. Pakistan flora is enriched with phytochemicals due to a diverse range of land. Phytochemicals, including volatile and non-volatile compounds, have captured much interest due to their numerous health advantages and significance in daily diet. The present study aimed to conduct in-depth metabolomic profiling of Pakistani-grown fenugreek leaves (Trigonella foenum-graecum), fennel seeds (Foeniculum vulgare), mint leaves (Mentha royleana), coriander seeds (Coriandrum sativum) and basil leaves (Ocimum basilicum) by using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–mass spectrometry (GC-MS). The first study was conducted to optimize extraction using different solvents (methanol, ethanol, chloroform, acetone, and water). Total phenolic content (TPC), total flavonoid content (TFC), and total condensed tannins (TCT) were quantified along with the antioxidant and anti-diabetic activities. The highest TPC (125.42 ± 10.89 mg GAE/g) and the highest antioxidant and anti-diabetic potential were quantified in mint. Seventy-one phytochemical metabolites were identified using LC-MS/MS, while forty-nine volatile constituents were identified using the GC-MS. A positive correlation was identified between phenolic contents and their biological activities. Furthermore, molecular docking helped to find drug molecules with more excellent anti-diabetic activity based on their binding affinities. This study suggests that selected medicinal herbs from Pakistan have significant nutraceutical and phytopharmaceutical potential. This study could further help in drug discovery.

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristic of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and consequently reduce the post-prandial raise of plasma glucose, which can reduce the risk of long-term diabetes complications. Hence, natural products are well-known sources for the discovery of new scaffold for drugs discovery, including new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach pass, Eastern Cape, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4) and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with IC50 values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1 and 3 respectively as ORAC (25789.9 ± 10.5; 23961.8 ± 14.1; 23939.3 ± 2.4) µM TE/g; 1 and 2 as FRAP (3917.8 ± 2.1; 1522.3 ± 0.9) µM AAE/g; 5 and 2 as TEAC (3190.4 ± 2.8; 2055.0 ± 2.6) µM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and anti-diabetic activities that can be useful to modulate oxidative stress, and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Background: The global prevalence of anxiety and depressive symptoms in adolescents has increased considerably during the COVID-19 pandemic. Mental health problems may compromise glycemic control in young people with type 1 diabetes; however, evidence of improved glycemic control in adolescents with T1D appeared early during the pandemic. This qualitative study aimed to provide a more in-depth understanding of how the COVID-19 pandemic affected adolescents with type 1 diabetes routines, experiences, T1D management, behaviors, and mental health. Methods: 24 adolescents, aged 15-18 years, with DM1, joined the discussion of focus groups in the context of the summer camp for diabetes. Word frequency and thematic analysis were conducted on adolescents’ narratives. Results: The word Frequency Analysis identified 'friends', 'family', and 'home' as the most frequent terms. Seven themes were identified: (1) COVID-19 and T1D; (2) emotional reactions to the COVID-19 pandemic; (3) changes in daily life; (4) feelings of loss; (5) coping with the COVID-19 pandemic; (6) the COVID-19 pandemic as an opportunity; (7) return to (new) normality. Conclusions The COVID-19 pandemic may have represented a more stressful condition for adolescents with DM1, facing additional challenges compared to their healthy peers. The results offer directions to the diabetes care team for a customized intervention while the consequences of the pandemic on adolescents’ health continue.

BACKGROUND: Patients with diabetic foot ulcers (DFU) and chronic limb-threatening ischemia (CLTI are at higher risk for major amputations and mortality. The aim of this study was to assess the safety and cost-efficacy of intramuscular injection of autologous monocyte-rich PRP platelet-rich plasma Tropocells® PRP (Estar Medical, Holon, Israel) in diabetic patients with chronic limb-threatening ischemia (CLTI) in which revascularization was not feasible. METHODS: a retrospective study was carried out on a series of patients with type 2 diabetes, grade Texas 3C or D DFU, and CLTI. All patients had undergone at least a previous revascularization and were allocated to a surgery waiting list for major amputation. According to the data provided by the manufacturer (https://www.zuccatobiotech.it/index.php/prodotti/tropocells), the monocyte-rich PRP kit obtained a platelet-rich plasma with a high concentration of peripheral blood mononuclear cells (with a proportionately lower amount of lymphocytes), a low concentration of neutrophils and an almost complete depletion of red blood cells. All patients underwent a procedure of local infiltration of autologous mononuclear cells through multiple perilesional and intramuscular injections of 10 mL PBMNC suspensions (0.2–0.3 mL in boluses) performed below the knee along the relevant vascular axis (anterior tibial artery and posterior tibial artery) at intervals of 1–2 cm and to a mean depth of 1.5–2 cm, using a 21 G needle. The procedures were performed according to the instructions of the manufacturer and were repeated at least two times (maximum 3 times) at intervals of 30 days. The principal endpoint was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoints were individual components of the primary endpoint, quality of life, any adverse events, and direct costs. All the endpoints were evaluated at 26 weeks. RESULTS: Out of 21 enrolled patients, 13 (61.9%) reached the primary endpoint, whereas three patients underwent a major amputation, and two patients died. The median TpCO2 was significantly increased, and pain was significantly reduced. The overall mean and median cost per patient were 9,255±7,328€ and 4,001 [2,991;7,565]€, respectively. CONCLUSIONS: the use of PBMNCs implants in patients with DFU and no-option CLTI seems to be efficacious in reducing the risk of major amputation and improve ulcer healing.

Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural ones is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and ef-fective strategy to include them in the diets of diabetic and obese people is through beverages. This review aimed to report the anti-diabetic potential of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase en-zymes, and to improve glucose uptake. In vivo, the beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable and fruit-based functional beverages to be a natural innovative therapy for the management of diabetes.

Introduction. The use of probiotics demonstrate efficacy against obesity and metabolic syndrome (MetS). Detection effective probiotic strains for hyperglycemia and immunity associated with is important task. The aim of the study was to evaluate an influence of Lactobacillus casei IMV B-7280 separately and composition L. casei IMV B-7280 / Bifidobacterium animalis VKB / B. animalis VKL on the levels of blood glucose and immunity in obese mice. Meterials and methods. Obesity was induced by fat-enriched diet (FED) in male BALB/c mice. Obese mice were transferred to standard diet and received per os probiotic strains daily during 10 days. We measured tumor necrosis factor-a (TNF-a) in blood serum using enzyme-linked immunosorbent assay and functional activity of peritoneal exudate macrophages (PEMs). Glucose levels in blood was defined with glucometer. Results. We ascertained that all probiotic strains induced reducing mice weight and visceral fat, normalization of TNF-a production and functional activity of PEMs. Treatment with L. casei IMV B-7280 was associated with decreasing blood glucose levels. No normalization of glucose and TNF-a levels in obese mice, transferred to standard diet without probiotic treatment, although we revealed decreasing their weight and visceral fat and partial recover of functional activity of PEMs. Conclusions. Probiotic strain L. casei IMV B-7280 (separately) and composition L. casei IMV B-7280 / B. animalis VKB / B. animalis VKL can re-equilibrate metabolic and inflammation indices in mouse obesity model. L. casei IMV B-7280 alone was more efficient in decreasing glucose levels than composition of strains.

Hemangioblasts give rise to endothelial progenitor cells (EPCs), which also express the cell surface markers CD133 and C-kit. They may differentiate into the outgrowth endothelial cells (OECs) that control neovascularization in the developing embryo. Reduced levels of EPC in circulation have been linked to human cardiovascular disorders, according to numerous studies. Furthermore, preeclampsia and senescence have been linked to levels of EPCs produced from cord blood. Uncertainties surround how preeclampsia affects the way EPCs function. It is reasonable to speculate that preeclampsia may have an impact on the function of fetal EPCs during the in utero period; however, given the present literature's suggestion that maternal vasculopathies, including preeclampsia, damage fetal circulation. Additionally, the differentiation potential and general activity of EPCs may serve as an indicator of the health of the fetal vascular system since they promote neovascularization and repair during pregnancy. Thus, the purpose of this review is to compare, through assessment of their quantity, differentiation potency, angiogenic activity, and senescence, the angiogenic function of fetal EPCs obtained from cord blood for normal and pregnancy problems. This will shed light on the relationship between the angiogenic function of fetal EPCs and pregnancy complications, which could have an effect on the management of long-term health issues like metabolic and cardiovascular disorders in offspring with abnormal vasculature development.

Background: Currently, limited number of therapeutic options are available to treat Diabetes mellitus, and to find a potential candidate, laboratory work takes time and also needs animal studies. So, the aim of this study was to determine the efficacy of some natural phytocompounds with the aid of molecular docking, bioinformatics and in silico drug design approaches. Method: Two proteins (Human CYP3A4 linked to metformin and Human dipeptidyl peptidase-IV) were selected and molecular docking studies were conducted using Pymol, AutoDock Vina, PyRx, and Discovery Studio. Different important pharmacokinetic parameters like ADME and toxicity data were obtained from online databases SwissADME and pkCSM program. Results: It was found that human dipeptidyl peptidase-IV (PDB ID: 4A5S) has exhibited a maximal affinity of -9.7 Kcal/mol for bryonolic acid and hesperidin, but only -6.7 kcal/mol for metformin hydrochloride. Similarly, the highest affinity of hesperidin for human CYP3A4 bound to metformin (PDB ID: 5G5J) is -10.7 Kcal/mol compared to metformin hydrochlor (-6.3 Kcal/mol). Besides, all the compounds have been documented outstanding ADMET profile, and accepted by drug-likeness or Lipinski rule. Conclusions: The present study suggested that these compounds can be further investigated in vitro and in vivo to establish them as lead compounds against Diabetes mellitus..

The number of diabetic patients worldwide is increasing rapidly. Prevention of diabetic reti-nopathy (DR), a leading cause of blindness, is a serious issue. We examined the effects of prophy-lactic pattern scanning laser retinal photocoagulation on DR development in 16 Spontaneously Diabetic Torii (SDT) fatty rats. Photocoagulation was applied to the right eyes of 8-week SDT fatty rats, and the left eyes served as the untreated controls. Electroretinography at 9 and 39 weeks of age and pathological examination of the retinal thickness and number of retinal folds, and immunohistochemistry of vascular endothelial growth factor and glial fibrillary acidic pro-tein at 24 and 40 weeks of age were performed bilaterally. No significant differences were seen between the left and right eyes in the apex latency and the amplitude of the oscillatory potential wave in the SDT fatty rats at 9 and 39 weeks of age and in the pathology and immunohistochem-istry in the SDT fatty rats at 24 and 40 weeks of age. Prophylactic pattern scanning retinal laser photocoagulation did not affect the development of DR in SDT fatty rats.

Diabetes management requires constant monitoring and individualized adjustments. This study proposes a novel approach that leverages digital twins and Personal Health Knowledge Graphs (PHKGs) to revolutionize diabetes care. Our key contribution lies in developing a real-time, patient-centric digital twin framework built on PHKGs. This framework integrates data from diverse sources, adhering to HL7 standards and enabling seamless information access and exchange. PHKGs offer a flexible and efficient format that supports various applications. As new knowledge about the patient becomes available, the PHKG can be easily extended to incorporate it. This dynamic approach fosters continuous improvement and facilitates the development of new applications. As proof of concept, we have demonstrated the versatility of our digital twin by applying it to different use cases in diabetes management. These include predicting glucose levels, optimizing insulin dosage, providing personalized lifestyle recommendations, and visualizing health data. By enabling real-time, patient-specific care, this research paves the way for more precise and personalized healthcare interventions, potentially improving long-term diabetes management outcomes.

Secondary metabolites such as flavonoids are considered to be promising in the treatment of NAFLD, which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated with regard to their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from STZ-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose-dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver TG levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

The identification of fetal cells in the blood and tissues of healthy mothers raised questions about the potential alloreactive origins of various diseases, such as autoimmunity, diabetes, arteriosclerosis, and cancer. However, the extent to which alloreactivity contributes to these diseases remains unverified. This study presents a basic mathematical disease model based on the genes’ origin and immunological interactions. This model, grounded in set theory, classifies these immunological interactions based on their intrinsic, extrinsic, and allogeneic nature. Therefore, this model offers an unexpected common theoretical foundation for understanding alloreactivity, genetic diseases, and infections. Furthermore, this model provides a valuable framework for scrutinizing the role of alloreactivity in health and disease.

Life is supported by metabolism, a vital physiological activity. It guarantees enough energy available to power every cellular activity. The primary cellular substrate, glucose, is where the majority of the energy needed by the cell to support all other life activities and the growth of living creatures is derived. The quality of life is greatly impacted by any disease or flaw that alters the metabolism of glucose. There is no known cure for the metabolic illness known as diabetes. As diabetes is so varied, the only effective treatments would be based on precision medicine and a molecular strategy. This review covers a wide range of topics, including the ability to recognize the various forms of diabetes, the anthropogenic and genetic influence of the cause of diabetes, the severity of the various forms of diabetes, its potential existential risk, the disease burden, and clinical methods for diagnosing them. The most recent research goes on to recommend ways to ameliorate the disease, including diet-based management, biotherapies, and other individual lifestyle choices. Futuristic therapy using molecular biology approach was suggested. Recent research found a direct correlation between an individual's lifestyle and the rate of gene mutation in diabetes. There is an existential risk associated with the sickness as the rate of the spread of the disease among population globally is faster than the world's population growth rate. It is possible to think of diabetes as a silent pandemic.

Understanding the biology underlying the mechanisms and pathways regulating pancreatic β-cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin producing β-cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β-cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic β-cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive toβ-cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1⁺/NKX6.1⁺), warrants their future commitment to monohormonal β-cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1⁺/NKX6.1^-) results in an undesirable generation of non-functional polyhormonal β-cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β-cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a mean to increase β-cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β-cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.

Endothelial integrity plays a major role in homeostasis and is responsive to the numerous endogenous factors released. While its functional role in vascular tone is well described, its role in the pathophysiology of cardiovascular disease is of interest as a potential therapeutic target. We performed a systematic review to provide an overview of new therapeutic and diagnostic targets for the treatment of coronary artery disease related to endothelial dysfunction. Databases of PubMed, Ovid’s version of MEDLINE, and EMBASE were interrogated with appropriate search terms. 28 studies met inclusion criteria and were included in the final systematic review. We identified inflammation, pulmonary hypertension, diabetes mellitus and Fabry disease as pathophysiological mechanisms and explored the therapeutic options related to these conditions including medications such as Canakinumab. Endothelial dysfunction has a key role in several different pathophysiological processes which can be targeted for therapeutic options. Ongoing research should be targeted at making the transition to clinical practice. Further research is also needed on understanding the amelioration of endothelial dysfunction with the use of cardiovascular medications.

Rho guanosine triphosphatases (GTPases) are key regulators in a number of cellular functions, including actin cytoskeleton remodeling and vesicle traffic. Traditionally, Rho GTPases are studied because of their function in cell migration and cancer, while their roles in metabolism are less documented. However, emerging evidence implicates Rho GTPases as regulators of processes of crucial importance for maintaining metabolic homeostasis. Thus, the time is now ripe for reviewing Rho GTPases in the context of metabolic health. Rho GTPase-mediated key processes include the release of insulin from pancreatic β-cells, glucose uptake into skeletal muscle and adipose tissue, and muscle mass regulation. Through the current review, we cast light on the important role of Rho GTPases in skeletal muscle, adipose tissue, and the pancreas and mechanisms by which Rho GTPases act to regulate glucose metabolism in health and disease. We also describe challenges and goals for future research.

Abstract: Objective: To assess both individual and interactive effects of prenatal medical conditions depression and Diabetes, and health behaviors including smoking during pregnancy on infant birth defects. Methods: The data for this research study were collected by the Pregnancy Risk Assessment Monitoring System (PRAMS) in 2018. Birth certificate records were used in each participating jurisdiction to select a sample representative of all women who delivered a live-born infant. Complex sampling weights were used to analyze the data with a weighted sample size of 4,536,867. Descriptive statistics were performed to explore frequencies of the independent and dependent variables. Bivariate and multivariable analyses were conducted to examine associations among the independent and dependent variables. Results: The results indicate and significant interaction between the variables smoking and Depression and Depression and Diabetes (OR= 3.17; p-value <0.001 and OR= 3.13; p-value <0.001 respectively). Depression during pregnancy was found to be strongly associated with delivering an infant with a birth defect (OR= 1.31, P-value < 0.001). Conclusion: Depression during pregnancy and its interaction with smoking and Diabetes are vital in determining birth defects in infants. The results indicate that birth defects in the United States can be lowering Depression in pregnant women.

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.

Our findings indicate that all five phytocannabinoids reduce HG-HL-induced -cell loss likely through reducing apoptosis and pyroptosis. The protective effects of CBD, THCV, CBC, and CBN were seen in the GSIS impairment by HG-HL. Although all five phytocannabinoids tested in this research demonstrated the capability to inhibit β-cell dedifferentiation induced by HG-HL, CBD seems to be more effective compared to the other phytocannabinoids, as indicated by the specific biomarker responses of β-cells and progenitor cells to CBD.

Metabolic syndrome (MS), a complex pathology with features like abnormal body fat distribution, insulin resistance, and dyslipidaemia, contributes to higher cardiovascular (CV) risk. A cross-sectional study including 87 individuals, assessed CV risk in elderly patients with type 2 diabetes and MS in Algarve, Portugal. The 10-year CV risk was estimated using the ADVANCE risk score calculator. The reductions in CV risk were estimated by adjusting the data inputted on the online tool to achieve systolic blood pressure (SBP) <130 or <120 mmHg, and LDL-cholesterol <70 mg/dL. Beyond waist circumference, the mean number of clinical features of MS was 3.14±0.84, without significant sex differences. The mean CV risk was 22.5% (CI: 20.3-24.7). Sex-specific analysis showed higher risk in males (24.2%, CI: 21.3-27.0) vs. females (19.7%, CI: 16.2-23.3; p=0.028). Hypothetical risk reductions show that lowering SBP to <130 mmHg could significantly lower the risk by an average of 9.2% (CI: 7.7-10.7), whereas 34.5% of the participants would be out of the diagnostic criteria for MS. When comparing each potential intervention with current risk, all interventions significantly reduce the 10-years CV risk. The study highlights the potential of blood pressure control in reducing CV risk and the importance of multifaceted risk reduction strategies.

Background: The diagnosis of metabolic syndrome (MetS) is a challenge in people with spinal cord injury (SCI). We aimed at identifying clinical risk factors or early markers of MetS in SCI that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. Methods: 168 patients with chronic (>1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Results: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in minutes/week (OR: 0.998, 95%CI: 0.996, 0.999) and more severe pain symptoms as assessed by numeral rating scale (OR: 1.353, 95%CI: 1.085, 1.793). Conclusions: In patients with SCI, intense pain symptoms and poor LTPA may suggest a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insu-lin-sensitivity and comorbidities.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

Insulin resistance is the most important underlying cause of obesity and type 2 Diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits, widely known for their antioxidant properties, have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety, compliance and efficacy of mangosteen on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. 22 patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (HOmeostatic Model Assessment-Insulin Resistance, HOMA-IR -53.22% vs -15.23%, p=.0037), and a trend decrease in inflammation markers serum levels, together with trend greater weight loss and trend increased HDL levels. No side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible role of mangosteen in the treatment of obesity, insulin resistance and inflammation.

Atherosclerosis is associated with vascular diseases, diabetes, and cancers. The Jumonji C-domain-containing 6 (JMJD6) gene plays an important role in diverse biological processes. In addition, autoantibodies are reportedly useful in the early diagnosis and treatment of many diseases. Here, JMJD6 was identified by serological identification of antigens by recombinant cDNA expression cloning as an antigen recognized by serum IgG from patients with unstable angina pectoris. Then, we performed amplified luminescent proximity homogeneous assay-linked immunosorbent assay using purified recombinant antigens and found elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with atherosclerosis-related diseases including ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers including esophageal cancer (EC), gastric cancer, lung cancer, and mammary cancer, compared with those in healthy donors. The s-JMJD6-Ab levels were closely associated with hypertension, habitual smoking, and the intima-media thickness, an atherosclerosis index. The better postoperative survival status was shown in patients with EC from the JMJD6-Ab-positive group than the negative group, especially from JMJD6-Ab-positive/PD-L1-negative group and JMJD6-Ab-positive/p53-Ab-negative group than JMJD6-Ab-negative/PD-L1-positive group and JMJD6-Ab-negative/p53-Ab-positive group, respectively. Hence, JMJD6 autoantibodies may reflect atherosclerosis severity, thereby a potential biomarker for atherosclerosis-related diseases including ischemic stroke, AMI, DM, and cancers and for predicting EC prognosis.