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Health to Eat A Smart Plate with Food Recognition, Classification, and Weight Measurement for Type-2 Diabetic Mellitus Patients Nutrition Control.

The management of type 2 diabetes mellitus (T2DM) is generally not only focused on pharmacological therapy. Medical nutrition therapy is often forgotten by patients for several reasons, such as difficulty determining the right nutritional pattern for themselves, regulating their daily nutritional patterns, or even not heeding nutritional diet recommendations given by doctors. Management of nutritional therapy is one of the important efforts that can be made by diabetic patients to prevent an increase in the complexity of the disease. Setting a diet with proper nutrition will help patients manage a healthy diet. The development of Smart Plate Health to Eat is a technological innovation that helps patients and users know the type of food, weight, and nutrients contained in certain foods. This study involved 50 types of food with a total of 30,800 foods using the YOLOv5s algorithm, where the identification, measurement of weight, and nutrition of food were investigated using a Chenbo load cell weight sensor (1 kg), an HX711 weight weighing AD module pressure sensor, and an IMX219-160 camera module (waveshare). The results of this study showed good identification accuracy in the analysis of four types of food rice (58%), braised quail eggs in soy sauce (60%), spicy beef soup (62%), and dried radish (31%), with accuracy for weight and nutrition (100%).

Tele-Assessment of Functional Capacity through the Six-Minute Walk Test in Patients with Diabetes Mellitus Type 2 Validity and Reliability of Repeated Measurements.

A tele-assessed 6MWT (TL 6MWT) could be an alternative method of evaluating functional capacity in patients with diabetes mellitus type 2 (DM2). This study aimed to assess the validity and reliability of a TL 6MWT. The functional capacity of 28 patients with DM2 (75% men) aged 61 ± 13 years was evaluated twice via an indoor, center-based 6MWT (CB 6MWT) and twice outside each patients home via a web-based platform TL 6MWT. The study showed a high statistically significant correlation between the CB and TL 6MWT (Pearsons

Lifestyle Intervention in NAFLD Long-Term Diabetes Incidence in Subjects Treated by Web- and Group-Based Programs.

Behavioral programs are needed for prevention and treatment of NAFLD and the effectiveness of a web-based intervention (WBI) is similar to a standard group-based intervention (GBI) on liver disease biomarkers. We aimed to test the long-term effectiveness of both programs on diabetes incidence, a common outcome in NAFLD progression. 546 NAFLD individuals (212 WBI, 334 GBI) were followed up to 60 months with regular 6- to 12-month hospital visits. The two cohorts differed in several socio-demographic and clinical data. In the course of the years, the average BMI similarly decreased in both cohorts, by 5% or more in 24.4% and by 10% or more in 16.5% of cases available at follow-up. After excluding 183 cases with diabetes at entry, diabetes was newly diagnosed in 48 cases during follow-up (31 (16.6% of cases without diabetes at entry) in the GBI cohort vs. 17 (9.7%) in WBI In individuals with NAFLD, WBI is as effective as GBI on the pending long-term risk of diabetes, via similar results on weight change.

Higher Adherence to Plant-Based Diet Lowers Type 2 Diabetes Risk among High and Non-High Cardiovascular Risk Populations A Cross-Sectional Study in Shanxi, China.

This study aimed to investigate the association between the plant-based diet index (PDI) score and T2D risk among residents of Shanxi Province, China, and explore whether the association was influenced by different levels of cardiovascular risk. A total of 50,694 participants aged 35-75 years were recruited between 2017 and 2019, and they were further divided into the high cardiovascular risk population (HCRP

Effects of Vitamin D on Cardiovascular Risk and Oxidative Stress.

Vitamin D has been primarily studied as an important factor influencing bone and calcium metabolism. Metabolites of vitamin D are essential for whole-body calcium homeostasis, maintaining serum calcium levels within a narrow range by regulating this process in the bones and gut. Nevertheless, its deficiency is also related to increased risk of type 2 diabetes mellitus (T2DM), metabolic syndrome (MS), and cardiovascular disease (CVD)-with increased visceral adipose tissue and body mass index (BMI), as well as the frequently associated hypercholesterolemia. It has been reported that vitamin D levels are inversely related to cardiovascular (CV) risk in men and women. However, the effects of vitamin D on distinct outcomes in women and the dose of supplementation needed to improve clinical endpoints have not been established. 25-Hydroxyvitamin D 25(OH)D reduces systemic inflammatory mediators in CVD and favors the release of anti-inflammatory cytokines from the immune system. In addition, 25(OH)D can be primarily converted into calcitriol (1,25-dihydroxycholecalciferol 1,25(OH)2D) in the kidneys through the action of the 1-α-hydroxylase enzyme. Calcitriol, through the downregulation mechanism of renin expression, renin-angiotensin-aldosterone system (RAAS) activity, and its interaction with the vitamin D receptor, can bring CV benefits. The calcitriol form also lowers parathyroid hormone (PTH) levels by indirectly causing a reduction in aldosterone and mineralocorticoid synthesis. Elevated plasma aldosterone is related to endothelial dysfunction and CVD in hypovitaminosis D status. Vitamin D supplementation may benefit certain risk groups, as it improves metabolic variables, reducing oxidative stress and CV outcomes. More studies are needed to define interventions with vitamin D in men and women.

Identification and Characterization of Genomic Predictors of Sarcopenia and Sarcopenic Obesity Using UK Biobank Data.

The substantial decline in skeletal muscle mass, strength, and gait speed is a sign of severe sarcopenia, which may partly depend on genetic risk factors. So far, hundreds of genome-wide significant single nucleotide polymorphisms (SNPs) associated with handgrip strength, lean mass and walking pace have been identified in the UK Biobank cohort however, their pleiotropic effects on all three phenotypes have not been investigated. By combining summary statistics of genome-wide association studies (GWAS) of handgrip strength, lean mass and walking pace, we have identified 78 independent SNPs (from 73 loci) associated with all three traits with consistent effect directions. Of the 78 SNPs, 55 polymorphisms were also associated with body fat percentage and 25 polymorphisms with type 2 diabetes (T2D), indicating that sarcopenia, obesity and T2D share many common risk alleles. Follow-up bioinformatic analysis revealed that sarcopenia risk alleles were associated with tiredness, falls in the last year, neuroticism, alcohol intake frequency, smoking, time spent watching television, higher salt, white bread, and processed meat intake whereas protective alleles were positively associated with bone mineral density, serum testosterone, IGF1, and 25-hydroxyvitamin D levels, height, intelligence, cognitive performance, educational attainment, income, physical activity, ground coffee drinking and healthier diet (muesli, cereal, wholemeal or wholegrain bread, potassium, magnesium, cheese, oily fish, protein, water, fruit, and vegetable intake). Furthermore, the literature data suggest that single-bout resistance exercise may induce significant changes in the expression of 26 of the 73 implicated genes in m. vastus lateralis, which may partly explain beneficial effects of strength training in the prevention and treatment of sarcopenia. In conclusion, we have identified and characterized 78 SNPs associated with sarcopenia and 55 SNPs with sarcopenic obesity in European-ancestry individuals from the UK Biobank.

Altered Expression of Antimicrobial Peptides in the Upper Gastrointestinal Tract of Patients with Diabetes Mellitus.

Antimicrobial peptides (AMP) are essential components of innate immunity with a broad range of antimicrobial activities against bacteria, viruses, and fungi. The aim of this study was to investigate AMP expression in the upper gastrointestinal tract in normal and pathological metabolic states in humans. Furthermore, we examined the correlation between vitamin D levels and AMP expression in the same cohort. Serum concentrations of 25-hydroxyvitamin D3 were measured, and mRNA expression of β-defensins HBD-1, -2, -3, -4, α-defensins HD-5 and -6 and cathelicidin in the upper gastrointestinal tract epithelia were determined by quantitative RT-PCR in 31 individuals (10 with type 2 diabetes, 10 with insulin resistance, and 11 healthy controls). The majority of the cohort showed low vitamin D concentrations, which were negatively correlated with mRNA expression levels of HBD-3 in corpus mucosa.

Medium-Term Nutritional and Metabolic Outcome of Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-S).

Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S), like other hypoabsorptive procedures, could be burdened by long-term nutritional deficiencies such as malnutrition, anemia, hypocalcemia, and hyperparathyroidism. We aimed to report our experience in terms of mid-term (2 years) bariatric, nutritional, and metabolic results in patients who underwent SADI-S both as a primary or revisional procedure. One hundred twenty-one patients were scheduled for SADI-S as a primary or revisional procedure from July 2016 to February 2020 and completed at least 2 years of follow-up. Demographic features, bariatric, nutritional, and metabolic results were analyzed during a stepped follow-up at 3 months, 6 months, 1 year and 2 years. Sixty-six patients (47 female and 19 male) were included. The median preoperative BMI was 53 (48-58) kgm SADI-S could be considered as an efficient and safe procedure with regard to nutritional status, at least in mid-term (2 years) results. It represents a promising bariatric procedure because of the excellent metabolic and bariatric outcomes with acceptable nutritional deficiency rates. Nevertheless, larger studies with longer follow-ups are necessary to draw definitive conclusions.

Sugar-Sweetened Beverages and Metabolic Risk in Children and Adolescents with Obesity A Narrative Review.

Sugar-sweetened beverages (SSBs) are major contributors of free sugars to the diet. A strong relationship between SSB intake and weight gain is described. we performed a narrative review to present an overview of the role of SSBs as a pivotal contributor in the development of obesity and metabolism-related complications. different factors influence SSB consumption in children, including economic variables, individual attributes and behaviors to environmental factors, parent features and parents behaviors. Data suggest that SSB intake has a negative effect on weight and obesity-related diseases. The leading mechanism linking SSB intake to the risk of gaining weight is decreased satiety and incomplete compensatory reduction in energy intake at meals following ingestion of liquid calories. Additionally, the effects of SSBs on gut microbiota and on eating behaviors were also reported. An association between SSB intake, weight gain and cardiometabolic risks is evident. Consumption of SSBs had a significant impact on the prevalence of obesity and related metabolic risks, including insulin resistance, type 2 diabetes, hypertension and metabolic syndrome. Limiting consumption of SSBs and increasing knowledge of the effect of SSBs on early metabolic and cardiovascular disorders will be useful in developing strategies to counteract the problem and to prevent obesity and related complications.Key future research areas for which further studies are needed include investigating the long-term effects of SSBs on health outcomes as well as analyzing the health effects of sugar consumed in solid compared to liquid forms and further elucidating the biological mechanisms of sugar addiction and energy compensation.

A Single Strain of

Type 2 diabetes (T2D) is usually accompanied by obesity and nonalcoholic fatty-liver-related insulin resistance. The link between T2D and dysbiosis has been receiving increasing attention. Probiotics can improve insulin sensitivity by regulating imbalances in microbiota, but efficacy varies based on the probiotic used. This study screened the main strain in the feces of healthy adult mice and found it to be a new

Associations between Conventional and Emerging Indicators of Dietary Carbohydrate Quality and New-Onset Type 2 Diabetes Mellitus in Chinese Adults.

Dietary glycemic index (GI), carbohydrate to fiber ratio (CF) and carbohydrate quality index (CQI) are conventional and emerging indicators for carbohydrate quality. We aimed to investigate the associations between these indicators and new-onset type 2 diabetes mellitus (T2DM) risk among Chinese adults. This prospective cohort study included 14,590 adults from the China Health and Nutrition Survey without cardiometabolic diseases at baseline. The associations between dietary GI, CF and CQI and T2DM risk were assessed using Cox proportional hazard regression analysis and dose-response relationships were explored using restricted cubic spline and threshold analysis. After a mean follow-up duration of 10 years, a total of 1053 new-onset T2DM cases occurred. There were U-shaped associations between dietary GI and CF and T2DM risk (both

New Advances in Metabolic Syndrome, from Prevention to Treatment The Role of Diet and Food.

The definition of metabolic syndrome (MetS) has undergone several changes over the years due to the difficulty in establishing universal criteria for it. Underlying the disorders related to MetS is almost invariably a pro-inflammatory state related to altered glucose metabolism, which could lead to elevated cardiovascular risk. Indeed, the complications closely related to MetS are cardiovascular diseases (CVDs) and type 2 diabetes (T2D). It has been observed that the predisposition to metabolic syndrome is modulated by complex interactions between human microbiota, genetic factors, and diet. This review provides a summary of the last decade of literature related to three principal aspects of MetS (i) the syndromes definition and classification, pathophysiology, and treatment approaches (ii) prediction and diagnosis underlying the biomarkers identified by means of advanced methodologies (NMR, LCGC-MS, and LC, LC-MS) and (iii) the role of foods and food components in prevention andor treatment of MetS, demonstrating a possible role of specific foods intake in the development of MetS.

Association between the Triglyceride-Glucose Index and Vitamin D Status in Type 2 Diabetes Mellitus.

Vitamin D deficiency (VDD) increases the risk for type 2 diabetes mellitus (T2DM), which might be related to insulin resistance (IR). We aimed to explore the association between the triglyceride-glucose (TyG) index, a reliable indicator of IR, and VDD in patients with T2DM. There were 1034 participants with T2DM enrolled in the Second Xiangya Hospital of Central South University. The TyG index was calculated as ln (fasting triglyceride (TG, mgdL) × fasting blood glucose (mgdL)2). VDD was defined as 25-hydroxyvitamin D 25(OH)D level <50 nmolL. Correlation analysis showed a negative association between the TyG index and 25(OH)D level. After adjustments for clinical and laboratory parameters, it was revealed that when taking the Q1 quartile of TyG index as a reference, an increasing trend of VDD prevalence was presented in the other three groups divided by TyG index quartiles, where the OR (95% CI) was 1.708 (1.132-2.576) for Q2, 2.041 (1.315-3.169) for Q3, and 2.543 (1.520-4.253) for Q4 (all Patients with higher TyG index were more likely to have an increased risk of VDD in T2DM population, which may be related to IR.

Standardized Ethanol Extract of

Obesity is a major cause of conditions such as type 2 diabetes and non-alcoholic fatty liver disease, posing a threat to public health worldwide. Here, we analyzed the anti-obesity effects of a standardized ethanol extract of

Effects of Glucomannan Supplementation on Type II Diabetes Mellitus in Humans A Meta-Analysis.

The hypoglycemic and lipid-lowering effects of glucomannan are widely known, and it is a potential effective treatment for type II diabetes. In this study, we evaluated the effects of glucomannan supplementation on blood-lipid-related indicators, blood-glucose-related indicators, blood pressure (BP), and body weight (BW) in patients suffering from type II diabetes. We searched databases including PubMed, Cochrane, the comprehensive biomedical research database (Embase), Web of Science, and China National Knowledge Infrastructure (CNKI) for literature on glucomannan and type II diabetes. Six randomized controlled trials (RCTs) were eligible (

Effectiveness of a Lifestyle Change Program on Insulin Resistance in Yaquis Indigenous Populations in Sonora, Mexico PREVISY.

To evaluate the effectiveness of the healthy lifestyle promotion program for Yaquis (PREVISY) on insulin resistance in the short- and medium-term periods in adults who are overweightobese and have an increased risk for diabetes. Using a translational research design, an intervention program was implemented in a sample of 93 Yaqui adult subjects. The effectiveness of PREVISY was evaluated by comparing the levels of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Triglycerides-Glucose Index (TyG index) at 6 and 12 months using a paired

Cocoa Flavanol Supplementation and the Effect on Insulin Resistance in Females Who Are Overweight or Obese A Randomized, Placebo-Controlled Trial.

There is interest in the impact that dietary interventions can have on preventing the transition from insulin resistance to type 2 diabetes, including a suggestion that the bioactive components of cocoa may enhance fasting insulin sensitivity. However, a role for cocoa flavanols (CF) in reducing insulin resistance in the insulin-stimulated state, an important risk factor for cardiovascular disease, is unresolved. This study investigated whether CF consumption improved whole-body insulin-mediated glucose uptake (M) in females with overweightobesity, using a randomized, double-blinded, placebo-controlled, parallel-group design. Thirty-two premenopausal females (19-49 years 27-35 kg·m

Comparable Hemodilution with Hypertonic Glucose in Patients with and without Type-2 Diabetes Mellitus during Hemodialysis.

(1) Background It was examined whether glucose-induced changes in the relative blood volume are suitable to identify subjects with and without type-2 diabetes mellitus (T2D) during hemodialysis. (2) Methods The relative blood volume was continuously recorded during hemodialysis and perturbed by the infusion of glucose comparable to the dose used for intravenous glucose tolerance tests. Indices of glucose metabolism were determined by the homeostatic model assessment (HOMA). Body composition was measured by a bioimpedance analysis. The magnitude and the time course of hemodilution were described by a modified gamma variate model and five model parameters. (3) Results A total of 34 subjects were studied, 14 with and 20 without T2D. The magnitude of the hemodilution and the selected model parameters correlated with measures of anthropometry, body mass index, absolute and relative fat mass, volume excess, baseline insulin concentration, and HOMA indices such as insulin resistance and glucose disposition in a continuous analysis, but were not different in a dichotomous analysis of patients with and without T2D. (4) Conclusions Even though the parameters of the hemodilution curve were correlated with measures of impaired glucose metabolism and body composition, the distinction between subjects with and without T2D was not possible using glucose-induced changes in the relative blood volume during hemodialysis.

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People-A Cohort Trial.

Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (

Egg Intake Is Associated with Lower Risks of Impaired Fasting Glucose and High Blood Pressure in Framingham Offspring Study Adults.

The association between egg consumption and cardiometabolic risk factors such as high blood pressure (HBP) and impaired fasting glucose (IFG) or type 2 diabetes (T2D) is still under debate. This study examines the association between egg consumption and these outcomes among 2349 30-64 year-old adults in the prospective Framingham Offspring Study. Diet was assessed using three-day dietary records. Potential confounders retained in the final models included age, sex, body mass index, and other dietary factors. The analysis of covariance and Cox proportional hazards models were used to assess the relevant continuous (i.e., FG, SBP, DBP) and categorical (i.e., T2D, HBP) outcomes. Consuming ≥5 eggs per week was associated with lower mean FG (

Development of a Semi-Quantitative Food Frequency Questionnaire to Estimate Macronutrient Intake among Type 2 Diabetes Mellitus Patients in Malaysia.

The Food Frequency Questionnaire (FFQ) is one of the most frequently used instruments in epidemiological studies for evaluating dietary intake. Because of the variety of dietary habits within different populations, an FFQ must be tailored to the specific group. To date, no specific FFQ has been developed for type 2 diabetes mellitus (T2DM) patients in Malaysia. In this study, we developed a semi-quantitative FFQ to estimate macronutrient intake among T2DM patients. The development of the FFQ was based on the data acquired from 150 respondents with T2DM from the southern part of Peninsular Malaysia who completed the three-day 24-h dietary recalls. The respondents were selected by convenience sampling. The mean intake from each food item and the proportions of macronutrients were calculated. The approach from a previous study was used to compile a list of foods items with a cumulative 90% macronutrient contribution that is significant for the nutrient of interest. In conclusion, we have successfully developed a new semi-quantitative FFQ with a total of 79 food items and nine food groups. The frequencies of the FFQ were divided into nine categories and this FFQ represents the usual food intake of T2DM patients in Malaysia. However, this tool has yet to be validated in patients with T2DM in Malaysia.

Effect of the Ketogenic Diet on the Prophylaxis and Treatment of Diabetes Mellitus A Review of the Meta-Analyses and Clinical Trials.

The exponentially growing frequency of diagnosing diabetes mellitus means that a verification of the previous dietetic approach to treating the disease seems justified. The simultaneous growth of interest in the ketogenic diet and the development of knowledge in this field have contributed to the increasingly frequent application of the ketogenic diet in diabetes treatment. This paper also deals with that issue its aim includes an extensive analysis of the influence of the ketogenic diet on the prophylaxis and treatment of diabetes. The paper has been prepared based on a wide, meticulous analysis of the available literature on the subject. Among other findings, a favorable effect of that nutrition model has been demonstrated on the values of glycated hemoglobin, glucose, insulin, or other metabolic parameters in diabetes patients. The effect of the ketogenic diet on the pharmacotherapy of type 1 and type 2 diabetes has been presented and compared with the standard nutritional management plan recommended for that disease. Further research is needed in this field, especially studies with a long follow-up period. The discussed articles report interesting therapeutic advantages to the ketogenic diet in comparison with standard diets.

Could Naringenin Participate as a Regulator of Obesity and Satiety

Obesity is a serious health problem worldwide, since it is associated with multiple metabolic disorders and complications such as cardiovascular disease, type 2 diabetes, fatty liver disease and overall metabolic dysfunction. Dysregulation of the hunger-satiety pathway, which includes alterations of central and peripheral signaling, explains some forms of obesity by favoring hyperphagia and weight gain. The present work comprehensively summarizes the mechanisms by which naringenin (NAR), a predominant flavanone in citrus fruits, could modulate the main pathways associated with the development of obesity and some of its comorbidities, such as oxidative stress (OS), inflammation, insulin resistance (IR) and dyslipidemia, as well as the role of NAR in modulating the secretion of enterohormones of the satiety pathway and its possible antiobesogenic effect. The results of multiple in vitro and in vivo studies have shown that NAR has various potentially modulatory biological effects against obesity by countering IR, inflammation, OS, macrophage infiltration, dyslipidemia, hepatic steatosis, and adipose deposition. Likewise, NAR is capable of modulating peptides or peripheral hormones directly associated with the hunger-satiety pathway, such as ghrelin, cholecystokinin, insulin, adiponectin and leptin. The evidence supports the use of NAR as a promising alternative to prevent overweight and obesity.

Cardiovascular Protection with a Long-Acting GLP-1 Receptor Agonist Liraglutide An Experimental Update.

Angiotensin II (Ang II), a peptide hormone generated as part of the renin-angiotensin system, has been implicated in the pathophysiology of many cardiovascular diseases such as peripheral artery disease, heart failure, hypertension, coronary artery disease and other conditions. Liraglutide, known as an incretin mimetic, is one of the glucagon-like peptide-1 (GLP-1) receptor agonists, and has been proven to be effective in the treatment of cardiovascular disorders beyond adequate glycemic control. The objective of this review is to compile our recent experimental outcomes-based studies, and provide an overview the cardiovascular protection from liraglutide against Ang II- and pressure overload-mediated deleterious effects on the heart. In particular, the mechanisms of action underlying the inhibition of oxidative stress, vascular endothelial dysfunction, hypertension, cardiac fibrosis, left ventricular hypertrophy and heart failure with liraglutide are addressed. Thus, we support the notion that liraglutide continues to be a useful add-on therapy for the management of cardiovascular diseases.

Anthocyanins Potential Therapeutic Approaches towards Obesity and Diabetes Mellitus Type 2.

Overweight and obesity are present in about three-quarters of the adult population in Mexico. The inflammatory mechanisms subjacent to visceral white adipose tissue are accountable for the initiation and development of cardiometabolic alterations, including type 2 diabetes. Lifestyle changes are pillars within its therapeutics and, thus, current dietary modifications should include not only hypocaloric prescriptions with balanced macronutrient intake, preferably by increasing the amount of whole grains, fruits, vegetables, nuts and legumes, but in concomitance, bioactive substances, such as anthocyanins, have been correlated with lower incidence of this disease.

SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol.

SGLT2 (Sodium-glucose Cotransporter-2) inhibitors are newer glucose-lowering drugs with many cardiovascular benefits that are not fully understood yet. Endothelial integrity plays a key role in cardiovascular homeostasis. 25-hydroxycholesterol (25-OHC), which is a proatherogenic stimuli that impairs endothelial barrier functions. VE-cadherin is an endothelial-specific protein crucial in maintaining endothelial integrity. The aim of this study was to assess the influence of SGLT2i on the integrity of endothelial cells interrupted by 25-OHC. We also aimed to evaluate whether this effect is associated with changes in the levels of VE-cadherin. We pre-incubated HUVECs with 10 μgmL of 25-hydroxycholesterol (25-OHC) for 4 h and then removed it and incubated endothelial cells with 1 μM of empagliflozin, 1 μM canagliflozin, or 1 μM dapagliflozin for 24 h. The control group included HUVECs cultured with the medium or with 25-OHC 10 μgmL. The integrity of endothelial cells was measured by the RTCA-DP xCELLigence system, and VE-cadherin was assessed in confocal microscopy. Our results show that SGLT2 inhibitors significantly increase endothelial integrity in comparison to medium controls, and they improve endothelial cell integrity interrupted by 25-OHC. This effect is associated with significant improvements in VE-cadherin levels. SGLT2i empagliflozin, canagliflozin, and dapagliflozin have a beneficial effect on the endothelial cell integrity and VE-cadherin levels reduced by 25-OHC.

Identification of Phytochemicals in Bioactive Extracts of

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay.

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC

Association between Type 1 Diabetes Mellitus and Periodontal Diseases.

Gingivitis and periodontitis are chronic inflammatory diseases that affect the supporting tissues of the teeth. Although induced by the presence of bacterial biofilms, other factor, such as tobacco smoking, drugs, and various systemic diseases, are known to influence their pathogenesis. Diabetes

The Belgian Diabetes in Pregnancy Follow-Up Study (BEDIP-FUS) A Multi-Centric Prospective Cohort Study on the Long-Term Metabolic Risk across Different Degrees of Gestational Glucose Intolerance Methodology and Design.

The Belgian Diabetes in Pregnancy follow-up study (BEDIP-FUS) aims to investigate the impact of body mass index (BMI), adiposity and different degrees of glucose intolerance on the metabolic profile and future risk for type 2 diabetes (T2D) in women and offspring five years after delivery in the BEDIP study. The BEDIP study was a prospective cohort study to evaluate different screening strategies for gestational diabetes (GDM) based on the 2013 WHO criteria. The aim of the BEDIP-FUS is to recruit 375 women-offspring pairs, stratified according to three different subgroups based on the antenatal result of the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during the BEDIP pregnancy. The follow-up visit consists of a 75 g OGTT, anthropometric measurements and questionnaires for the mothers, and a fasting blood sample with anthropometric measurements for the child. Primary outcome for the mother is glucose intolerance defined by the American Diabetes Association criteria and for the offspring the BMI z-score. Recruitment began in January 2021. The BEDIP-FUS study will help to better individualize follow-up in women with different degrees of hyperglycemia in pregnancy and their offspring.

The Role of Pharmacists and Community Pharmacies in the Screening, Knowledge, and Awareness of Diabetes Mellitus Type 2 in Jordanian People Visiting Community Pharmacies.

According to the International Diabetes Federation (IDF), diabetes is increasing exponentially worldwide and will become more prevalent than ever in the Middle East by 2045, with a 110% increase. This study aims to clarify the role of pharmacists and community pharmacies in the screening, knowledge, and awareness of Type 2 diabetes among Jordanian people who visit community pharmacies in Amman, Jordan. Study design This was a cross-sectional prospective study that was conducted from September to December 2021 in Amman, Jordan. Data were collected using a standardized questionnaire that was composed of multiple parts. The first part collected information on demographics, residence, educational level, and insurance status the second part was composed of 14 knowledge assessing questions the last part was composed of the American Diabetes Association (ADA) diabetes risk score card test. Additionally, after confirming that each participant had returned their completed sheets, participants who scored greater than 5 had their blood sugar levels checked using a finger-prick blood test. The questionnaire was administered in person by a trained researcher. Using Slovins formula, a 95% confidence interval (CI), and a 0.05 margin of error, the sample size was determined to be 267 participants. The study included 305 participants. Descriptive and regression analyses were performed by using the Statistical Package for Social Science (SPSS) with a significance level of A significant relationship was found between specialty (medical education) and the knowledge of risk factors for Type 2 diabetes mellitus (T2DM), ( Random visitors to Jordanian community pharmacies are expected to benefit from awareness and educational campaigns. These test results revealed a lack of knowledge, indicating the need for education to dispel myths and highlight the serious risks associated with T2DM. The study discovered that participants understanding of diabetes disease prevention through lifestyle and dietary changes was inadequate. A specialist-led educational program may increase knowledge among visitors who participate. In order to prevent the spread of diabetes, more campaigns and health-promoting and prevention educational activities are required.

Effects of Mind-Body Training as a Mental Health Therapy in Adults with Diabetes Mellitus Type II A Systematic Review.

The increase in the prevalence and disease burden of diabetes has highlighted the need to strengthen a comprehensive care system that includes mental health treatment. A systematic review was carried out to analyze the effectiveness of mind-body training as a therapy for the mental health management of adult patients with type 2 diabetes mellitus (T2DM) following the PRISMA 2020 guidelines. Pubmed, Scopus and Web of Science databases were consulted between November and December 2022. Eight articles were selected according to the inclusion and exclusion criteria. Only randomized controlled trials were included. The interventions focused on mindfulness and yoga with variable durations of between 8 weeks and 6 months. Four of the included studies observed statistically significant changes (

Two Distinct Groups Are Shown to Be at Risk of Diabetes by Means of a Cluster Analysis of Four Variables.

Recent attempts to classify adult-onset diabetes using only six diabetes-related variables (GAD antibody, age at diagnosis, BMI, HbA1c, and homeostatic model assessment 2 estimates of b-cell function and insulin resistance (HOMA2-B and HOMA2-IR)) showed that diabetes can be classified into five clusters, of which four correspond to type 2 diabetes (T2DM). Here, we classified nondiabetic individuals to identify risk clusters for incident T2DM to facilitate the refinement of prevention strategies. Of the 1167 participants in the population-based Iwaki Health Promotion Project in 2014 (baseline), 868 nondiabetic individuals who attended at least once during 2015-2019 were included in a prospective study. A hierarchical cluster analysis was performed using four variables (BMI, HbA1c, and HOMA2 indices). Of the four clusters identified, cluster 1 (n 103), labeled as obese insulin resistant with sufficient compensatory insulin secretion, and cluster 2 (n 136), labeled as low insulin secretion, were found to be at risk of diabetes during the 5-year follow-up period the multiple factor-adjusted HRs for clusters 1 and 2 were 14.7 and 53.1, respectively. Further, individuals in clusters 1and 2 could be accurately identified the area under the ROC curves for clusters 1and 2 were 0.997 and 0.983, respectively. The risk of diabetes could be better assessed on the basis of the cluster that an individual belongs to.

Lipoprotein(a), Cardiovascular Events and Sex Differences A Single Cardiological Unit Experience.

Lipoprotein(a)-Lp(a), which retains proatherogenic and prothrombotic properties, may be modified by hormonal and metabolic factors. However, few studies have focused on differences related to sex and cardiometabolic risk factors in the relationship between Lp(a) and cardiovascular disease, especially in terms of prognosis. This study aimed at evaluating the predictive value of Lp(a) (cut-off 30 mgdL) for hard events (HEs mortality and non-fatal myocardial infarction) according to sex and cardiometabolic risk factors in 2110 patients (1501 males, mean age 68 ± 9 years) undergoing coronary angiography for known or suspected coronary artery disease. There were 211 events over a median follow-up period of 33 months. Lp(a) > 30 mgdL did not confer a worse prognosis on the overall population. However, Kaplan-Meier subgroup analysis evidenced a worse prognosis in type 2 diabetes (T2D) females with elevated Lp(a) (log-rank test

Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells.

Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood. As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in many tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism. However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many diseases, such as Alzheimers disease, cancer, fatty liver disease and type-2 diabetes, treatment with gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase in intracellular triglycerides (SH-SY5Y 170.3% HEK 272.1% Calu-3 448.1%), suggesting that the decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which could be important in diseases, such as Alzheimers disease.

Hepatic Glucose Metabolism Disorder Induced by Adipose Tissue-Derived miR-548ag via DPP4 Upregulation.

The present study aimed to explore the molecular mechanism underlying the regulation of glucose metabolism by miR-548ag. For the first time, we found that miR-548ag expression was elevated in the abdominal adipose tissue and serum of subjects with obesity and type 2 diabetes mellitus (T2DM). The conditional knockout of adipose tissue

Advanced Glycation End-Products and Diabetic Neuropathy of the Retina.

Diabetic retinopathy is a tissue-specific neurovascular impairment of the retina in patients with both type 1 and type 2 diabetes. Several pathological factors are involved in the progressive impairment of the interdependence between cells that consist of the neurovascular units (NVUs). The advanced glycation end-products (AGEs) are one of the major pathological factors that cause the impairments of neurovascular coupling in diabetic retinopathy. Although the exact mechanisms for the toxicities of the AGEs in diabetic retinopathy have not been definitively determined, the AGE-receptor of the AGE (RAGE) axis, production of reactive oxygen species, inflammatory reactions, and the activation of the cell death pathways are associated with the impairment of the NVUs in diabetic retinopathy. More specifically, neuronal cell death is an irreversible change that is directly associated with vision reduction in diabetic patients. Thus, neuroprotective therapies must be established for diabetic retinopathy. The AGEs are one of the therapeutic targets to examine to ameliorate the pathological changes in the NVUs in diabetic retinopathy. This review focuses on the basic and pathological findings of AGE-induced neurovascular abnormalities and the potential therapeutic approaches, including the use of anti-glycated drugs to protect the AGE-induced impairments of the NVUs in diabetic retinopathy.

Prolactin in Pregnancies Affected by Pre-Existing Maternal Metabolic Conditions A Systematic Review.

Women affected by maternal pregestational diabetes mellitus (type 1 or type 2) or by polycystic ovary syndrome experience an increased risk of pregnancy complications, as well as suboptimal lactation outcomes. The hormone prolactin plays important roles in pregnancy and postpartum, both as a metabolic and lactogenic hormone. We aimed to explore, through a systematic review, the relationship between pregestational maternal metabolic conditions and prolactin levels in pregnancy and postpartum. MEDLINE via OVID, CINAHL Plus, and Embase were searched from inception to 9 May 2022. Eligible studies included women who were pregnant or up to 12 months postpartum and had a pre-existing diagnosis of type 1 or type 2 diabetes mellitus or polycystic ovary syndrome with reporting of at least one endogenous maternal serum prolactin level during this time. Two independent reviewers extracted the data. Eleven studies met the eligibility criteria. The studies were too diverse and heterogeneous to enable meta-analysis. Overall, prolactin levels appeared to be lower in pregnancies affected by type 1 diabetes mellitus. There was little data in polycystic ovary syndrome or type 2 diabetes pregnancy, but prolactin increment across pregnancy in polycystic ovary syndrome emerged as an area for future study. During postpartum, lactation difficulties in women with metabolic disease present before pregnancy are well-described, but the relationship to prolactin remains unclear. Overall, preliminary evidence suggests that pre-existing maternal metabolic disease may alter prolactin dynamics in pregnancy and postpartum. Further well-designed studies in modern cohorts, with standardised collection and serial sampling across pregnancy and postpartum, are required to clarify these associations.

Therapeutic Advances in Diabetic Kidney Disease.

Although sodium glucose co-transporter type 2 (SGLT-2) inhibitors were initially introduced as glucose-lowering medications, it was later discovered that cardiorenal protection is the most important treatment effect of these agents. A triad of landmark trials consistently showed the benefits of SGLT-2 inhibitors on kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD), irrespective of the presence or absence of Type 2 diabetes (T2D). Furthermore, finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that safely and effectively improved cardiorenal outcomes in a large Phase 3 clinical trial program that included >13,000 patients with T2D and a wide spectrum of CKD. These two drug categories have shared and distinct mechanisms of action, generating the hypothesis that an overadditive cardiorenal benefit with their combined use may be biologically plausible. In this article, we describe the mechanism of action, and we provide an overview of the evidence for cardiorenal protection with SGLT-2 inhibitors and the nonsteroidal MRA finerenone in patients with CKD associated with T2D.

Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus.

Diabetes is currently the fifth leading cause of death by disease in the USA. The underlying mechanisms for type 2 Diabetes Mellitus (DM2) and the enhanced susceptibility of such patients to inflammatory disorders and infections remain to be fully defined. We have recently shown that peripheral blood mononuclear cells (PBMCs) from non-diabetic people upregulate expression of inflammatory genes in response to proteasome modulators, such as bacterial lipopolysaccharide (LPS) and soybean lectin (LEC) in contrast, resveratrol (RES) downregulates this response. We hypothesized that LPS and LEC will also elicit a similar upregulation of gene expression of key signaling mediators in (PBMCs) from people with type 2 diabetes (PwD2, with chronic inflammation) ex vivo. Unexpectedly, using next generation sequencing (NGS), we show for the first time, that PBMCs from PwD2 failed to elicit a robust LPS- and LEC-induced gene expression of proteasome subunit LMP7 (

Health Benefits of Coffee Consumption for Cancer and Other Diseases and Mechanisms of Action.

Coffee is one of the most widely consumed beverages worldwide, and epidemiology studies associate higher coffee consumption with decreased rates of mortality and decreased rates of neurological and metabolic diseases, including Parkinsons disease and type 2 diabetes. In addition, there is also evidence that higher coffee consumption is associated with lower rates of colon and rectal cancer, as well as breast, endometrial, and other cancers, although for some of these cancers, the results are conflicting. These studies reflect the chemopreventive effects of coffee there is also evidence that coffee consumption may be therapeutic for some forms of breast and colon cancer, and this needs to be further investigated. The mechanisms associated with the chemopreventive or chemotherapeutic effects of over 1000 individual compounds in roasted coffee are complex and may vary with different diseases. Some of these mechanisms may be related to nuclear factor erythroid 2 (Nrf2)-regulated pathways that target oxidative stress or pathways that induce reactive oxygen species to kill diseased cells (primarily therapeutic). There is evidence for the involvement of receptors which include the aryl hydrocarbon receptor (AhR) and orphan nuclear receptor 4A1 (NR4A1), as well as contributions from epigenetic pathways and the gut microbiome. Further elucidation of the mechanisms will facilitate the potential future clinical applications of coffee extracts for treating cancer and other inflammatory diseases.

Oxidation State in Peritoneal Dialysis in Patients with Type 2 Diabetes Mellitus.

End-stage renal disease (ESRD) progression is closely related to oxidative stress (OS). The study objective was to determine the oxidant and antioxidant status in peritoneal dialysis (PD) patients with type 2 diabetes mellitus (DM). An analytical cross-sectional study from the PD program was carried out with 62 patients, 22 with and 40 without DM. Lipoperoxides (LPO) levels in patients with DM, 3.74 ± 1.09 mML, and without DM, 3.87 ± 0.84 mML were found to increase compared to healthy controls (HC) 3.05 ± 0.58 mML (

Biological Activity of Selenium and Its Impact on Human Health.

Selenium (Se) is a naturally occurring metalloid element essential to human and animal health in trace amounts but it is harmful in excess. Se plays a substantial role in the functioning of the human organism. It is incorporated into selenoproteins, thus supporting antioxidant defense systems. Selenoproteins participate in the metabolism of thyroid hormones, control reproductive functions and exert neuroprotective effects. Among the elements, Se has one of the narrowest ranges between dietary deficiency and toxic levels. Its level of toxicity may depend on chemical form, as inorganic and organic species have distinct biological properties. Over the last decades, optimization of population Se intake for the prevention of diseases related to Se deficiency or excess has been recognized as a pressing issue in modern healthcare worldwide. Low selenium status has been associated with an increased risk of mortality, poor immune function, cognitive decline, and thyroid dysfunction. On the other hand, Se concentrations slightly above its nutritional levels have been shown to have adverse effects on a broad spectrum of neurological functions and to increase the risk of type-2 diabetes. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important issue to elucidate its effect on human diseases. This review gives an overview of the role of Se in human health highlighting the effects of its deficiency and excess in the body. The biological activity of Se, mainly performed through selenoproteins, and its epigenetic effect is discussed. Moreover, a brief overview of selenium phytoremediation and rhizofiltration approaches is reported.

Melatonin Mitigates iNOS-Related Effects of HEMA and Camphorquinone in Human Dental Pulp Cells Relevance for Postoperative Sensitivity Mechanism in Type 2 Diabetes.

High elution and diffusion of 2-hydroxylethyl methacrylate (HEMA) and camphorquinone (CQ) through dentinal tubules may induce pulp injury and postoperative sensitivity. We aimed to investigate the melatonin protective effect in HEMA- and CQ-treated human dental pulp cells (hDPCs) as well as its relevance in a mechanism for postoperative sensitivity in diabetic patients. hDPCs were exposed to HEMA (5 mM) andor CQ (1 mM) in the absence and presence of melatonin (MEL) (0.1 mM and 1 mM). Heme oxygenase-1 (HMOX1), NADPH oxidase-4 (NOX4), BCL-2-associated X-protein (BAX), B-cell lymphoma-2 (BCL-2) and caspase-3 (CASP3) gene expression levels, and superoxide dismutase (SOD) activity were measured in hDPCs while inducible nitric oxide synthase (iNOS) and melatonin protein expression were measured in human dental pulp as well, by RT-PCR, by ELISA, and spectrophotometrically. Bioinformatic analyses were performed by using the ShinyGO (v.0.75) application. Type 2 diabetic patients showed a higher incidence of postoperative sensitivity and lower melatonin and higher iNOS content in dental pulp tissue compared with non-diabetic patients. Melatonin, when co-added in hDPC culture, reverses HEMA and CQ cytotoxic effects via anti-apoptotic and anti-inflammatoryantioxidant iNOS-related effects. Enrichment analyses showed that genesproteins, altered by HEMA and CQ and normalized by melatonin, are the most prominently overrepresented in type 2 diabetes mellitus pathways and that they share subcellular localization in different oligomeric protein complexes consisting of anti- and pro-apoptotic regulators. This is the first evidence of the ability of melatonin to counteract iNOS-mediated inflammatory and stress effects in HEMA- and CQ-treated hDPCs, which could be of significance for the modulation of presently observed immediate postoperative sensitivity after composite restoration in type 2 diabetic patients.

Triterpenoids from Kochiae Fructus Glucose Uptake in 3T3-L1 Adipocytes and

In this study, three new triterpenes (

Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease.

Peroxisome proliferator activated receptors, including PPARα, PPARβδ, and PPARγ, are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They play important roles in glucose and lipid metabolism and are also supposed to reduce inflammation and atherosclerosis. All PPARs are involved in angiogenesis, a process critically involved in cardiovascular pathology. Synthetic specific agonists exist for all PPARs. PPARα agonists (fibrates) are used to treat dyslipidemia by decreasing triglyceride and increasing high-density lipoprotein (HDL) levels. PPARγ agonists (thiazolidinediones) are used to treat Type 2 diabetes mellitus by improving insulin sensitivity. PPARαγ (dual) agonists are supposed to treat both pathological conditions at once. In contrast, PPARβδ agonists are not in clinical use. Although activators of PPARs were initially considered to have favorable effects on the risk factors for cardiovascular disease, their cardiovascular safety is controversial. Here, we discuss the implications of PPARs in vascular biology regarding cardiac pathology and focus on the outcomes of clinical studies evaluating their benefits in cardiovascular diseases.

Finerenone, a Non-Steroidal Mineralocorticoid Receptor Antagonist, Reduces Vascular Injury and Increases Regulatory T-Cells Studies in Rodents with Diabetic and Neovascular Retinopathy.

Vision loss in diabetic retinopathy features damage to the blood-retinal barrier and neovascularization, with hypertension and the renin-angiotensin system (RAS) having causal roles. We evaluated if finerenone, a non-steroidal mineralocorticoid receptor (MR) antagonist, reduced vascular pathology and inflammation in diabetic and neovascular retinopathy. Diabetic and hypertensive transgenic (mRen-2)27 rats overexpressing the RAS received the MR antagonist finerenone (10 mgkgday, oral gavage) or the angiotensin-converting enzyme inhibitor perindopril (10 mgkgday, drinking water) for 12 weeks. As retinal neovascularization does not develop in diabetic rodents, finerenone (5 mgkgday, i.p.) was evaluated in murine oxygen-induced retinopathy (OIR). Retinal vasculopathy was assessed by measuring gliosis, vascular leakage, neovascularization, and VEGF. Inflammation was investigated by quantitating retinal microgliamacrophages, pro-inflammatory mediators, and anti-inflammatory regulatory T-cells (Tregs). In diabetes, both treatments reduced systolic blood pressure, gliosis, vascular leakage, and microglialmacrophage density, but only finerenone lowered VEGF, ICAM-1, and IL-1ß. In OIR, finerenone reduced neovascularization, vascular leakage, and microglial density, and increased Tregs in the blood, spleen, and retina. Our findings, in the context of the FIDELIO-DKD and FIGARO-DKD trials reporting the benefits of finerenone on renal and cardiovascular outcomes in diabetic kidney disease, indicate the potential of finerenone as an effective oral treatment for diabetic retinopathy.

Advanced Glycation End Products Effects on Adipocyte Niche Stiffness and Cell Signaling.

Adipose tissue metabolism under hyperglycemia results in Type II diabetes (T2D). To better understand how the adipocytes function, we used a cell culture that was exposed to glycation by adding intermediate carbonyl products, which caused chemical cross-linking and led to the formation of advanced glycation end products (AGEs). The AGEs increased the cells and their niche stiffness and altered the rheological viscoelastic properties of the cultured cells leading to altered cell signaling. The AGEs formed concomitant with changes in protein structure, quantified by spectroscopy using the 8-ANS and Nile red probes. The AGE effects on adipocyte differentiation were viewed by imaging and evidenced in a reduction in cellular motility and membrane dynamics. Importantly, the alteration led to reduced adipogenesis, that is also measured by qPCR for expression of adipogenic genes and cell signaling. The evidence of alteration in the plasma membrane (PM) dynamics (measured by CTxB binding and NP endocytosis), also led to the impairment of signal transduction and a decrease in AKT phosphorylation, which hindered downstream insulin signaling. The study, therefore, presents a new interpretation of how AGEs affect the cell niche, PM stiffness, and cell signaling leading to an impairment of insulin signaling.

Interactions between Bitter Taste Receptor Gene Variants and Dietary Intake Are Associated with the Incidence of Type 2 Diabetes Mellitus in Middle-Aged and Older Korean Adults.

The relationship between the variants of bitter taste receptor gene

Identification of Genipin as a Potential Treatment for Type 2 Diabetes.

The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of β-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic β-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca

An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism.

Obesity and type 2 diabetes are associated with defects of insulin action in different tissues or alterations in β-cell secretory capacity that may be triggered by environmental challenges, inadequate lifestyle choices, or an underlying genetic predisposition. In addition, recent data shows that obesity may also be caused by perturbations of the gut microbiota, which then affect metabolic function and energy homeostasis in the host. Maintenance of metabolic homeostasis in complex organisms such as mammals requires organismal-level communication, including between the different organs and the gut microbiota. Extracellular vesicles (EVs) have been identified in all domains of life and have emerged as crucial players in inter-organ and inter-kingdom crosstalk. Interestingly, EVs found in edible vegetables or in milk have been shown to influence gut microbiota or tissue function in mammals. Moreover, there is a multidirectional crosstalk mediated by EVs derived from gut microbiota and body organs that has implications for host health. Untangling this complex signaling network may help implement novel therapies for the treatment of metabolic disease.

The Correlation between Waist Circumference and the Pro-Inflammatory Adipokines in Diabetic Retinopathy of Type 2 Diabetes Patients.

Central obesity is one of the major risk factors for type 2 diabetes mellitus (DM), and the most common complication of DM is diabetic retinopathy. However, the exact relationship between obesity and DR remains unknown. In this study, we evaluate the effect of obesity on DR by comparing the aqueous humor-derived adipokines. For the analysis, 37 DR patients and 29 non-DR-patients participated. To evaluate the obesity of the patients, body mass index (BMI) and waist circumference (WC) were used. By comparing the concentrations of adipokines obtained from the aqueous humor of the two groups, the relationship between DR and adipokines was analyzed. In addition, by analyzing the correlation between obesity and adipokines in patients, the relationship between central obesity and DR was finally confirmed. The WC was significantly higher in patients than in the non-patient group. The concentrations of all adipokines compared in this study were significantly higher in the DR group than in the non-DM group (

Potential Impact of Non-Steroidal Mineralocorticoid Receptor Antagonists in Cardiovascular Disease.

Inappropriate mineralocorticoid receptor (MR) activation in different cardiovascular cell types has deleterious effects on cardiac remodeling and function. Therefore, MR inhibition is a crucial pharmacological strategy to overcome cardiovascular dysfunction. Despite efficient blockade of MR with steroidal MR antagonists (MRAs), their clinical application is unsatisfactory due to the adverse effects. Newer non-steroidal MRAs with greater potency could be suitable for clinical application, especially in patients with type 2 diabetes mellitus and chronic kidney disease. Although clinical evidence has shown the beneficial effects of non-steroidal MRAs on cardiovascular outcomes in patients with heart failure with reduced ejection fraction, clinical trials are ongoing to evaluate the efficacy of heart failure with preserved ejection fraction. Therefore, comparative pharmacological characterization of non-steroidal MRAs over classic steroidal MRAs is crucial. Here, we summarize the pre-clinical evidence of non-steroidal MRAs, which suggests an improvement in cardiac dysfunction, as well as the underlying molecular mechanisms in animal models mimicking different clinical conditions. In addition, we discuss up-to-date information from clinical trials regarding the beneficial effects of non-steroidal MRAs on meaningful cardiovascular outcomes. Both pre-clinical and clinical evidence support treatment with non-steroidal MRAs in patients with cardiovascular disease.

Effects of Nutritionally Induced Obesity on Metabolic Pathways of Zebrafish.

Human obesity has become a global epidemic that can lead to many metabolic diseases, including insulin resistance, type 2 diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver. The development of obesity is closely associated with excess food intake and energy imbalance, family history, lifestyle, psychology and other factors, but molecular mechanisms underlying the induction and development of obesity remain to be intensively studied under a variety of internal and external pathogenesis conditions. In this study, we generated two obesity models of zebrafish that were treated with a high-fat diet (HFD) or an overfeeding diet (DIO). Both HFD and DIO zebrafish exhibited higher levels of lipid accumulation, fat distribution, microvascular steatosis and ectopic accumulation of lipid droplets in liver and muscle than normal diet (NOD) fish. The comparison of transcriptome sequencing data for the livers of HFD, DIO and NOD groups identified common and specific genes and signaling pathways that are potentially associated with zebrafish obesity induced by HFD andor DIO. These findings provide clues for further understanding the mechanisms of obesity development and preventing nutritionally induced obesity through targeting the common signaling pathways and biological processes.

The Black Box Orchestra of Gut Bacteria and Bile Acids Who Is the Conductor

Over the past decades the potential role of the gut microbiome and bile acids in type 2 diabetes mellitus (T2DM) has been revealed, with a special reference to low bacterial alpha diversity. Certain bile acid effects on gut bacteria concern cytotoxicity, or in the case of the microbiome, bacteriotoxicity. Reciprocally, the gut microbiome plays a key role in regulating the bile acid pool by influencing the conversion and (de)conjugation of primary bile acids into secondary bile acids. Three main groups of bacterial enzymes responsible for the conversion of bile acids are bile salt hydrolases (BSHs), hydroxysteroid dehydrogenases (HSDHs) and enzymes encoded in the bile acid inducible (Bai) operon genes. Interventions such as probiotics, antibiotics and fecal microbiome transplantation can impact bile acids levels. Further evidence of the reciprocal interaction between gut microbiota and bile acids comes from a multitude of nutritional interventions including macronutrients, fibers, prebiotics, specific individual products or diets. Finally, anatomical changes after bariatric surgery are important because of their metabolic effects. The heterogeneity of studies, diseases, bacterial species and (epi)genetic influences such as nutrition may challenge establishing specific and detailed interventions that aim to tackle the gut microbiome and bile acids.

Metabolic Control, Diabetic Complications and Drug Therapy in a Cohort of Patients with Type 1 and Type 2 Diabetes in Secondary and Tertiary Care between 2004 and 2019.

This paper studies the features of metabolic parameters, diabetic complications and drug therapy of a single-centre cohort of patients with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) in secondary care and tertiary care over a 15-year period. Retrospective cross-sectional analysis of four single-centre cohorts between 2004 and 2019. All patients with T1DM or T2DM in secondary care ( Diabetes duration increased in both patients with T1DM and T2DM in secondary care and tertiary care ( The increased prevalence of complications is likely due to older age and longer diabetes duration. Low rates of hypoglycaemia, lower limb amputations and good glycaemic control in secondary care patients indicate a good structure of patient care.

Association of Lung Fibrotic Changes and Cardiological Dysfunction with Comorbidities in Long COVID-19 Cohort.

Association of Metabolic Syndrome and Other Factors with the Presence of Diabetic Nephropathy in Type 2 Diabetic Patients.

Diabetic nephropathy (DN) is a severe diabetes mellitus (DM) complication that contributes to medical and financial burdens. This study aimed to investigate risk factors for DN among type 2 diabetes mellitus (T2DM) patients by stratifying the participants based on the presence of metabolic syndrome (MetS). Between June 2017 and June 2022, Taiwan Hospital was chosen for this retrospective case-control study. Following the completion of a standardized interview and the donation of blood samples for this study, participants were divided into two groups according to whether they had MetS. We contrasted how the potential DN-related factors impacted these two groups. A total of 1212 patients were included, and 639 patients (52.7%) had MetS. Multivariable analysis showed that the level of educational qualifications, fasting glucose, and uric acid (UA) were associated with DN. However, chewing betel nut behavior, higher systolic blood pressure (SBP), and higher glycated hemoglobin (HbA1c) were found to be risk factors of DN among the patients who had both T2DM and MetS. Notably, betel nut chewing increased the chance of DN in T2DM patients with MetS. This study found that the level of education, chewing betel nut behavior, HbA1c, fasting glucose, SBP, and UA were significant risk factors for the development of DN in diabetic individuals with concurrent MetS. Our research reveals that managing the aforementioned risk factors is crucial to lowering the prevalence of DN, particularly in individuals with lower levels of education.

Perceived Knowledge, Attitude, and Practices (KAP) and Fear toward COVID-19 among Patients with Diabetes Attending Primary Healthcare Centers in Kuwait.

To assess perceived fear and to evaluate the level of knowledge, attitude, and prevention practices (KAP) regarding COVID-19 infection among patients with diabetes mellitus (DM) attending primary healthcare centers (PHCs) in Kuwait. This will help evaluate gaps and provide appropriate support to limit the spread of COVID-19 infection in high-risk patients. A descriptive cross-sectional study was carried out using a self-administered questionnaire. All patients aged 18 years or older attending for follow-up or newly diagnosed with type 1 or type 2 diabetes were eligible to participate in the study. Patients waiting for their regular follow-up appointments at the PHCs were invited verbally to take part in the study. The study excluded patients under the age of 18 and those with significant cognitive or physical impairment that might interfere with independent self-care behavior. The questionnaire included 57 items. The data were analyzed using descriptive statistics. A total of 294 questionnaires were distributed to patients at PHCs in three health districts (Hawally, Capital, and Farwaniya) in Kuwait 251 patients agreed to participate in the study, yielding a response rate of 85.4%. The study showed that most patients had moderate knowledge (71.1%) of COVID-19. The majority of correctly responded questions were about the mode of COVID-19 transmission, the most common clinical presentations, and at-risk people. On the other hand, 83.7% (n 210) identified common cold symptoms (stuffy nose, runny nose, and sneezing) as COVID-19 symptoms. More than half of the patients (n 146, 58.2%) were unable to identify uncommon COVID-19 symptoms, such as diarrhea and skin rash or discoloration. Most patients had a positive attitude (90.9%) and good prevention practices (83.6%). The overall fear score of the participating patients was 21.6 ± 6.5 (61.7%). Regardless of the positive attitude and good preventive practices of the patients, they had moderate knowledge levels about COVID-19. This indicates that there are significant knowledge gaps that still need to be filled. Different strategies can be used for this purpose, such as social media and public information campaigns. Supporting psychological well-being is vital for at-risk patients during a pandemic.

COVID-19 Mortality in the Colorado Center for Personalized Medicine Biobank.

Over 6.37 million people have died from COVID-19 worldwide, but factors influencing COVID-19-related mortality remain understudied. We aimed to describe and identify risk factors for COVID-19 mortality in the Colorado Center for Personalized Medicine (CCPM) Biobank using integrated data sources, including Electronic Health Records (EHRs). We calculated cause-specific mortality and case-fatality rates for COVID-19 and common pre-existing health conditions defined by diagnostic phecodes and encounters in EHRs. We performed multivariable logistic regression analyses of the association between each pre-existing condition and COVID-19 mortality. Of the 155,859 Biobank participants enrolled as of July 2022, 20,797 had been diagnosed with COVID-19. Of 5334 Biobank participants who had died, 190 were attributed to COVID-19. The case-fatality rate was 0.91% and the COVID-19 mortality rate was 122 per 100,000 persons. The odds of dying from COVID-19 were significantly increased among older men, and those with 14 of the 61 pre-existing conditions tested, including hypertensive chronic kidney disease (OR 10.14, 95% CI 5.48, 19.16) and type 2 diabetes with renal manifestations (OR 5.59, 95% CI 3.42, 8.97). Male patients who are older and have pre-existing kidney diseases may be at higher risk for death from COVID-19 and may require special care.

Prevalence and Associations of Type 2 Diabetes Risk and Sociodemographic Factors in Saudi Arabia A Web-Based Cross-Sectional Survey Study.

Type 2 diabetes mellitus (T2DM) is a chronic disease with ever-increasing prevalence worldwide. In our study, we evaluated the prevalence of the risk of developing T2DM in Saudi Arabia and investigated associations between that risk and various sociodemographic characteristics. To those ends, a web-based cross-sectional survey of Saudi nationals without diabetes, all enrolled using snowball sampling, was conducted from January 2021 to January 2022. The risk of developing T2DM was evaluated using a validated risk assessment questionnaire (ARABRISK), and associations of high ARABRISK scores and sociodemographic variables were explored in multivariable logistic regression modeling. Of the 4559 participants, 88.1% were 18 to 39 years old, and 67.2% held a college or university degree. High ARABRISK scores were observed in 7.5% of the sample. Residing in a midsize city versus a large city was associated with a lower ARABRISK risk score (

Adherence to the Taiwan Daily Food Guide and the Risk of Type 2 Diabetes A Populational Study in Taiwan.

This study aims to examine whether adherence to the Taiwan Daily Food Guide relates to the risk of type 2 diabetes. A population-based study was conducted using data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2013-2016. Dietary intakes were assessed using a validated food-frequency questionnaire. Type 2 diabetes was defined as a fasting serum HbA1c level of 6.5% or higher or participants who have received treatment for type 2 diabetes or have reported a physician diagnosis of type 2 diabetes. A total of 2534 Taiwanese adults aged 19 and above were included. We found that the Daily Food Guide adherence was negatively associated with the prevalence of type 2 diabetes. The odds ratios (ORs) for those in the fourth quartile of the recommended total servings was 0.67 (95% confidence interval (CI) 0.45-0.99) compared with those in the first quartile. In addition, those who were men (OR 1.46, 95% CI 1.07-1.98), aged more than 50 to 65 (OR 6.48, 95% CI 2.57-16.35), or more than 65 (OR 6.81, 95% CI 2.56-18.08), with body mass index (BMI) of 24 to less than 27 (OR 2.08, 95% CI 1.55-2.79), had BMI of more than 27 (OR 3.63, 95% CI 2.73-4.83), had an education level of junior high and high school (OR 1.68, 95% CI 1.03-2.74), were divorced, separated, widowed, or refused to answer (OR 1.39, 95% CI 1.03-1.88) were associated with an increased prevalence of type 2 diabetes. In conclusion, people who adhere better to the Taiwan Daily Food Guide were found to have a reduced risk of type 2 diabetes.

Arsenic A Perspective on Its Effect on Pioglitazone Bioavailability.

Arsenic (As) is a common contaminant in drinking water in northeastern Mexico, which reduces the expression of cytochrome P450 (CYP 450). This enzyme group metabolizes numerous drugs, such as oral antidiabetic drugs such as pioglitazone (61% CYP 3A4, 49% CYP 2C8). When CYP 450s function is inadequate, it has decreased therapeutic activity in type 2 diabetes mellitus (T2DM). This study aimed to establish the effect of As on pioglitazone metabolism in patients with T2DM. Urine, water, and plasma samples from a healthy population ( The healthy and T2DM groups were exposed via drinking water to >0.010 ppm, Ka values with a factor of 4.7 higher, Cl 1.42 lower, and ABCt 1.26 times higher concerning the healthy group. In silico analysis (DFT) of CYP 3A4 and CYP 2C8 isoforms showed the substitution of the iron atom by As in the active sites of the enzymes. The results indicate that the substitution of Fe for As modifies the enzymatic function of CYP 3A4 and CYP 2C8 isoforms, altering the metabolic process of CYP 2D6 and CYP 3A4 in patients with T2DM. Consequently, the variation in metabolism alters the bioavailability of pioglitazone and the expected final effect.

The Associations of Loneliness and Social Support with Cognitive Impairment among Middle-Aged and Older Individuals with Diabetes.

Diabetes mellitus is a chronic disease with significant morbidity and mortality and it is associated with poor cognitive performance in later life. This study seeks to determine the relationship between social support and cognitive function among participants with type 2 diabetes mellitus (T2DM). We used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including participants with T2DM aged 45 and older (n 4821). We examined different aspects of perceived social support, measured as structural social support (e.g., marital status), functional social support (having a caregiver in case of sickness or disability), and loneliness. We examined cognitive functioning using a six-item screener. Our results indicate that adults who felt lonely for 5-7 days per week had almost double the odds of cognitive impairment compared to those who didnt feel lonely. These results suggest that among middle-aged and older individuals with T2DM, interventions targeting lonely adults and which aim to reduce loneliness may combat some of the risks of cognitive decline.

A Meta-Analysis of the Influence on Inflammatory Factors in Type 2 Diabetes among Middle-Aged and Elderly Patients by Various Exercise Modalities.

The purpose of this study was to investigate the effects of various exercise modalities on inflammatory factors in middle-aged and elderly patients with type 2 diabetes (MEPT2D), as lifestyle changes, such as physical activity and dietary modifications, are considered important in the prevention of type 2 diabetes. For the study methodology, Pubmed, CNKI, EBSCO, Wanfang Data, and Web of Science were selected for the search. The methodological quality of the included studies was assessed by the Cochrane Risk of Bias (ROB) tool, and statistically analyzed using the RevMan 5.4.1 analysis software, which included 18 investigations involving 853 study subjects. Meta-analysis findings indicated that aerobic training (AT), resistance training (RT), combined training (CT), and high-intensity interval training (HIIT) showed significant reductions in CRP, TNF-α, IL-6, and IL-10 levels in MEPT2D. Among them, HIIT was superior to other training modalities in reducing TNF-α levels, while CT was superior to AT, RT, and HIIT in decreasing IL-6, IL-10, and CRP in MEPT2D. Meanwhile, RT had limited effects in reducing CRP and TNF-α levels in MEPT2D. However, HIIT had no significant effect on IL-6 and IL-10 in MEPT2D. In conclusion, long-term regular AT, RT, CT, and HIIT all contributed to the reduction of inflammatory status (CRP, TNF-α, IL-6, and IL-10) in MEPT2D, while CT (for CRP, IL-6, and IL-10) and HIIT (for TNF-α) represent the best approaches to counteract the inflammatory response in MEPT2D.

Association between Physical Activity, Body Composition, and Metabolic Disorders in Middle-Aged Women of Ksar el Kebir (Morocco).

This study aimed to examine the association between physical activity (PA), body composition, and metabolic disorders in a population of Moroccan women classified by menopausal status. This cross-sectional study comprised 373 peri- and postmenopausal women aged 45-64 years old. PA levels were assessed using the short version of the International Physical Activity Questionnaire (IPAQ-SF). Body composition and metabolic disorders were assessed by measurements of anthropometric and biological parameters weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), WCHC ratio, percent body fat, systolic and diastolic blood pressure, fasting blood glucose, and serum lipids (total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C). Metabolic syndrome (MetS) was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Pearson correlations were used to test for associations. The mean total PA score of perimenopausal women was 1683.51 ± 805.36 MET-minweek, and of postmenopausal women was 1450.81 ± 780.67 MET-minweek. In all participants, peri- and postmenopausal women, PA was significantly and inversely associated with BMI, weight, percent body fat, HC, WC, and number of MetS components (

Low-Grade Inflammation and Role of Anti-Inflammatory Diet in Childhood Obesity.

At present, pediatric obesity is a significant public health concern. We have seen a surge of disorders that are obesity-related, e.g., insulin resistance (IR), type 2 diabetes mellitus (T2DM), high blood pressure, heart disease, stroke, cancer, non-alcoholic fatty liver disease (NAFLD), autoimmune disorders and many more. The mechanisms linking these diseases to excess body weight are related to low-grade inflammation (LGI). Although there is a limited number of studies assessing this immune process in childhood obesity, they indicate its significant importance for the health of future generations. There is a need for more research into the prevention and treatment of low-grade inflammation in childhood. The aim of this review is to present and discuss the process of cold inflammation, and its impact on health and anti-inflammation nutrition. A diet rich in anti-inflammatory nutrients may be the key to maintaining health, as well as recovery.

Intensity Differences of Resistance Training for Type 2 Diabetic Patients A Systematic Review and Meta-Analysis.

Resistance training is used as adjunctive therapy for type 2 diabetes (T2DM), and the aim of this study was to investigate the differences in the treatment effects of different intensities of resistance training in terms of glycemia, lipids, blood pressure, adaptations, and body measurements. A comprehensive search was conducted in the PubMed, EMBASE (Excerpta Medica dataBASE), EBSCO (Elton B. Stephens Company) host, Cochrane Library, WOS (Web of Science), and Scopus databases with a cut-off date of April 2022, and reference lists of relevant reviews were also consulted. The literature screening and data extraction were performed independently by two researchers. RoB2 (Risk of bias 2) tools were used for the literature quality assessment, the exercise intensity was categorized as medium-low intensity and high intensity, and the meta subgroup analysis was performed using R Version. A fixed or random effects model was selected for within-group analysis based on the heterogeneity test, and a random effects model was used for the analysis of differences between subgroups. A total of 36 randomized controlled trials were included, with a total of 1491 participants. It was found that resistance training significantly improved HbA1c (glycated hemoglobin), fasting blood glucose, TG (triglycerides), TC (total cholesterol), and LDL (low-density lipoprotein cholesterol) levels in patients with T2DM and caused a significant reduction in systolic blood pressure, percent of fat mass, and HOMA-IR (homeostatic model assessment for insulin resistance) indexes. The effects of high and medium-low intensity resistance training on T2DM patients were different in terms of HOMA-IR, maximal oxygen consumption, weight, waist-to-hip ratio, and body mass indexes. Only medium-low intensity resistance training resulted in a decrease in HOMA-IR. In addition to weight (MD 4.25, 95% CI 0.27, 8.22,

Metformin Therapy and Breast Cancer Incidence in the Hail Region.

Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease is related to insulin resistance and multiplied blood sugar ranges. Furthermore, it has been established that the use of metformin improves the menstrual cycles and ovulation rates of these women. A structured questionnaire was conducted to determine the prevalence of breast cancer among women using metformin in the Hail region. The incidence of breast cancer among women using metformin in the Hail region is very low. Thus, it can be said that breast cancer cases declined among diabetics taking metformin. This means that metformin use is associated with a lower risk of breast cancer in women with type 2 diabetes, even in cases where these women have a family history of breast cancer. According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study corroborate the literature on this subject by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes. However, further in vitro and in vivo experiments are crucial to investigate the protective effect of metformin against breast cancer and to confirm our findings.

Pharmacological Targeting of the RAGE-NFκB Signalling Axis Impedes Monocyte Activation under Diabetic Conditions through the Repression of SHP-2 Tyrosine Phosphatase Function.

Monocytes play a vital role in the development of cardiovascular diseases. Type 2 diabetes mellitus (T2DM) is a major CVD risk factor, and T2DM-induced aberrant activation and enhanced migration of monocytes is a vital pathomechanism that leads to atherogenesis. We recently reported the upregulation of SHP-2 phosphatase expression in mediating the VEGF resistance of T2DM patient-derived monocytes or methylglyoxal- (MG, a glucose metabolite and advanced glycation end product (AGE) precursor) treated monocytes. However, the exact mechanisms leading to SHP-2 upregulation in hyperglycemic monocytes are unknown. Since inflammation and accumulation of AGEs is a hallmark of T2DM, we hypothesise that inflammation and AGE-RAGE (Receptor-for-AGEs) signalling drive SHP-2 expression in monocytes and blockade of these pathways will repress SHP-2 function. Indeed, monocytes from T2DM patients revealed an elevated SHP-2 expression. Under normoglycemic conditions, the serum from T2DM patients strongly induced SHP-2 expression, indicating that the T2DM serum contains critical factors that directly regulate SHP-2 expression. Activation of pro-inflammatory TNFα signalling cascade drove SHP-2 expression in monocytes. In line with this, linear regression analysis revealed a significant positive correlation between TNFα expression and SHP-2 transcript levels in T2DM monocytes. Monocytes exposed to MG or AGE mimetic AGE-BSA, revealed an elevated SHP-2 expression and co-treatment with an NFκB inhibitor or genetic inhibition of p65 reversed it. The pharmacological inhibition of RAGE was sufficient to block MG- or AGE-BSA-induced SHP-2 expression and activity. Confirming the importance of RAGE-NFκB signalling in regulating SHP-2 expression, the elevated binding of NFκB to the SHP-2 promoter-induced by MG or AGE-BSA-was reversed by RAGE and NFκB inhibition. Besides, we detected elevated RAGE levels in human and murine T2DM monocytes and monocytes exposed to MG or AGE-BSA. Importantly, MG and AGE-BSA treatment of non-T2DM monocytes phenocopied the aberrant pro-migratory phenotype of T2DM monocytes, which was reversed entirely by either SHP-2- or RAGE inhibition. In conclusion, these findings suggest a new therapeutic approach to prevent accelerated atherosclerosis in T2DM patients since inhibiting the RAGE-NFκB-SHP-2 axis impeded the T2DM-driven, SHP-2-dependent monocyte activation.

Development of a Laser Microdissection-Coupled Quantitative Shotgun Lipidomic Method to Uncover Spatial Heterogeneity.

Lipid metabolic disturbances are associated with several diseases, such as type 2 diabetes or malignancy. In the last two decades, high-performance mass spectrometry-based lipidomics has emerged as a valuable tool in various fields of biology. However, the evaluation of macroscopic tissue homogenates leaves often undiscovered the differences arising from micron-scale heterogeneity. Therefore, in this work, we developed a novel laser microdissection-coupled shotgun lipidomic platform, which combines quantitative and broad-range lipidome analysis with reasonable spatial resolution. The multistep approach involves the preparation of successive cryosections from tissue samples, cross-referencing of native and stained images, laser microdissection of regions of interest, in situ lipid extraction, and quantitative shotgun lipidomics. We used mouse liver and kidney as well as a 2D cell culture model to validate the novel workflow in terms of extraction efficiency, reproducibility, and linearity of quantification. We established that the limit of dissectible sample area corresponds to about ten cells while maintaining good lipidome coverage. We demonstrate the performance of the method in recognizing tissue heterogeneity on the example of a mouse hippocampus. By providing topological mapping of lipid metabolism, the novel platform might help to uncover region-specific lipidomic alterations in complex samples, including tumors.

Ultrasound Renal Score to Predict the Renal Disease Prognosis in Patients with Diabetic Kidney Disease An Investigative Study.

Renal disease associated with type 2 diabetes mellitus (T2DM) has become the leading cause of chronic kidney disease (CKD). Renal ultrasonography is an imaging examination required in the work-up of renal disease. This study aimed to identify the differences in renal ultrasonographic findings between patients with and without DM, and to evaluate the relationship between renal ultrasound findings and renal prognosis in patients with DM. A total of 252 patients who underwent renal ultrasonography at Chungnam National University Hospital were included. Kidney disease progression was defined as a ≥10% decline in the annual estimated glomerular filtration rate (eGFR), which, in this paper, is referred to as ΔeGFRyear, or the initiation of renal replacement therapy after follow-up. The renal scoring system was evaluated by summing up the following items the value of renal parenchymal echogenicity (0 normal 1 mildly increased and 2 increased) and the shape of the cortical margin (0 normal and 1 irregular right kidney lengthheight (RH-0 or 1), mean cortical thicknessrenal lengthheight (CKH-0 or 1), and cortical thicknessparenchymal thickness (CKPK-0 or 1) based on the median 0-above median, and 1-below median). Patients with DM had thicker renal PKH than those without, despite having lower eGFRs (0.91 ± 0.15, 0.86 ± 0.14,

Association of Fatty Liver Index with Incident Diabetes Risk in Patients Initiating Statin-Therapy A 6-Year Retrospective Study.

Statins are associated with new-onset type 2 diabetes (T2D), mainly in patients with metabolic syndrome (MetS). The fatty liver index (FLI) is used as a prognostic score for the diagnosis of non-alcoholic fatty liver disease (NAFLD), which is common in patients with MetS. We aimed to investigate the association of FLI with new-onset T2D in patients initiating statin therapy. A retrospective observational study including 1241 individuals with dyslipidemia and followed up for ≥3 years. Patients with T2D and those receiving lipid-lowering treatment at the baseline visit were excluded. Models with clinical and laboratory parameters were used to assess the association of FLI with incident T2D. Among the 882 eligible subjects, 11% developed T2D during the follow-up (6 years IQR 4-10 years). After adjusting for sex, age and MetS parameters, a multivariate analysis revealed that age (HR1.05 95%CI 1.01-1.09, FLI is significantly and independently associated with new-onset T2D risk in patients initiating statin therapy.

Bioactive Compounds of Underground Valerian Extracts and Their Effect on Inhibiting Metabolic Syndrome-Related Enzymes Activities.

Extractions of the underground parts of valerian were prepared with water and ethanol (25-95%) at 25-75 °C. Extraction yields, bioactive compounds, and the 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability of lyophilized extracts were determined. The inhibitory effects of the extracts, valerenic acid derivatives and phenolic acids, on metabolic syndrome (MS)-related enzymes activities were further examined. Both roots and rhizomes extracted with 95% ethanol at 75 °C had the highest levels of bioactive compounds. The antioxidant capacity and inhibition of MS-related enzymes of the roots extract were better than those of the rhizomes. The roots extract more strongly inhibited pancreatic lipase (inhibition of 50% of enzyme activity (IC

Glycemic Responses of Milk and Plant-Based Drinks Food Matrix Effects.

The consumption of food items containing digestible carbohydrates in food products leads to postprandial increases in blood glucose levels and glycemic responses. The extent to which these occur depends on many factors, including concentration and type of carbohydrate, but also other physicochemical properties of the food matrix, which determine the rate of uptake of monosaccharides into the bloodstream, including product structure and factors affecting gastric emptying. For milk, control of postprandial glycemic responses appears to be multifaceted, including a controlled rate of gastric emptying, a rate of glucose and galactose uptake into the bloodstream controlled by enzymatic hydrolysis, as well as stimulated insulin secretion to enhance uptake of blood glucose from the bloodstream. Altogether, this allows milk to deliver comparatively high levels of carbohydrate with limited glycemic responses. For plant-based drinks positioned as milk alternatives, however, compositional differences (including carbohydrate type and concentration) as well as matrix factors limiting control over gastric emptying and insulin secretion can, in some cases, lead to much stronger glycemic responses, which are undesirable in relation to non-communicable diseases, such as type-2 diabetes. This review discusses glycemic responses to milk and plant-based drinks from this perspective, focusing on mechanistic insights and food matrix effects.

Association of adverse respiratory events with sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in South Korea a nationwide cohort study.

Impaired respiratory function remains underrecognized in patients with type 2 diabetes (T2D), despite common pulmonary impairment. Meanwhile, there is little data available on the respiratory effects of sodium glucose cotransporter 2 inhibitors (SGLT2i). Hence, we examined the association between SGLT2i use and the risk of adverse respiratory events in a real-world setting. We conducted a population-based, nationwide cohort study using an active-comparator new-user design and nationwide claims data of South Korea from January 2015 to December 2020. Among individuals aged 18 years or older, propensity score matching was done to match each new user of SGLT2is with dipeptidyl peptidase 4 inhibitors (DPP4is), with patients followed up according to an as-treated definition. The primary outcome was respiratory events, a composite endpoint of acute pulmonary edema, acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure. Secondary outcomes were the individual components of the primary outcome and in-hospital death. Cox models were used to estimate hazard ratios (HRs) and 95% CIs. Of 205,534 patient pairs in the propensity score matched cohort, the mean age of the entire cohort was 53.8 years and 59% were men, with a median follow-up of 0.66 years all baseline covariates achieved balance between the two groups. Incidence rates for overall respiratory events were 4.54 and 7.54 per 1000 person-years among SGLT2i and DPP4i users, respectively, corresponding to a rate difference of 3 less events per 1000 person-years (95% CI - 3.44 to - 2.55). HRs (95% CIs) were 0.60 (0.55 to 0.64) for the composite respiratory endpoint, 0.35 (0.23 to 0.55) for acute pulmonary edema, 0.44 (0.18 to 1.05) for ARDS, 0.61 (0.56 to 0.66) for pneumonia, 0.49 (0.31 to 0.76) for respiratory failure, and 0.46 (0.41 to 0.51) for in-hospital death. Similar trends were found across individual SGLT2is, subgroup analyses of age, sex, history of comorbidities, and a range of sensitivity analyses. These findings suggest a lower risk of adverse respiratory events associated with patients with T2D initiating SGLT2is versus DPP4is. This real-world evidence helps inform patients, clinicians, and guideline writers regarding the respiratory effects of SGLT2i in routine practice.

The effect of APN, hs-CRP and APNhs-CRP in periodontitis with DAA.

Common chronic infections induced low-grade inflammation has been correlated with atherosclerosis as supported by strong evidence. The balance between pro-and anti-inflammatory factors was exploited to elucidate the effects of chronic periodontitis on diabetes-associated atherosclerosis. Study subjects encompassed 30 SPF male rats randomly divided into four groups A group (NC), B group (T2DM), C group (CP), D group (DM CP). After developing the model, blood samples were collected from the angular vein analyze serum APN, hs-CRP, and blood lipid. the carotid artery was isolated for HE staining. Compared with group A, the serum APN in group B, C and D decreased gradually with the progression of the disease. Serum hs-CRP in group B, C and D was significantly increased. At T3, T4 and T5 in group B, C and D, APNhs-CRP significantly decreased. TC, LDL and TG significantly increased in group B, D HDL significantly decreased in group C. Carotid artery HE staining showed compared with group A, different degrees of endothelial defect, destruction of elastic fibers in the middle membrane, disorder of smooth muscle arrangement, and partial dissolution 、 fragmentation and Calcium salt deposition necrosis occurred in group B, C and D. Enhanced systemic inflammation, decreased adiponectin level, and disorganized lipid metabolism with or without type 2 diabetes attributed to local inflammation of periodontitis can result in an imbalance of pro-inflammatory and anti-inflammatory effects. Therefore, its more meaningful to predict the progression of DAA with anti-inflammatorypro-inflammatory variation.

Comparison of the ability of HOMA-IR, VAI, and TyG indexes to predict metabolic syndrome in children with obesity a cross-sectional study.

The increasing trend in childhood obesity needs to be closely monitored and intervened due to long-term health issues such as metabolic syndrome, cardiovascular diseases, hypertension, and type 2 diabetes. We aimed to determine and compare the cut-off values for the visceral adiposity index (VAI), triglyceride-glucose index (TyG), and HOMA-IR for predicting metabolic syndrome (MetS). This population-based cross-sectional study was conducted in May 2019 in Samsun, Turkey. The study included 169 children with obesity aged 9 and 10 years. After anthropometric and clinical evaluation, fasting blood samples were collected from the children. The areas under the curve of the visceral adiposity index, triglyceride-glucose index, and HOMA-IR were compared by receiver-operating-characteristic (ROC) analysis in predicting the MetS. The total prevalence of MetS was 21.3% in children with obesity, and it was two times higher in girls than in boys. The mean values of TyG and VAI were significantly different in those who have and have not MetS in both genders. However, the HOMA-IR index was higher only in girls with MetS and did not differ in boys by having MetS. The VAI and the TyG index both had statistically significant cut-off values in both sexes and a larger ROC area than the HOMA-IR index in predicting MetS. The VAI and TyG index are effective indicators in assessing the MetS risk in children with obesity. Both indexes can be considered useful tools in pediatric research and the evaluation of interventions. However, the HOMA-IR index formula needs to be developed taking into account age, gender, and ethnicity.

DNA methylation age acceleration is associated with risk of diabetes complications.

Patients with Type 2 diabetes mellitus (T2D) are at risk for micro- and macrovascular complications. Implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The epigenetic clock estimates an individuals biological age using DNA methylation profiles. In this study, we examined older adults of the Berlin Aging Study II that were reexamined on average 7.4 years after baseline assessment as part of the GendAge study. DNA methylation age (DNAmA) and its deviation from chronological age DNAmA acceleration (DNAmAA) were calculated with the 7-CpG clock (available at both timepoints, n 1,071), Horvaths clock, Hannums clock, PhenoAge and GrimAge (available at follow-up only, n 1,067). T2D associated complications were assessed with the Diabetes Complications Severity Index (DCSI). We report on a statistically significant association between oral glucose tolerance test results and Hannum and PhenoAge DNAmAA. PhenoAge was also associated with fasting glucose. In contrast, we found no cross-sectional association after covariate adjustment between DNAmAA and a diagnosis of T2D. However, longitudinal analyses showed that every additional year of 7-CpG DNAmAA at baseline increased the odds for developing one or more additional complications or worsening of an already existing complication during the follow-up period by 11% in male participants with T2D. This association persisted after covariate adjustment (OR 1.11, p 0.045, n 56). Although our results remain to be independently validated, this study shows promising evidence of utility of the 7-CpG clock in identifying patients with diabetes who are at high risk for developing complications. Deterioration of vision, kidney function and cardiovascular function are just a few examples of diabetes-related complications. However, not all patients develop these complications, and it is desirable to detect patients that have a high risk for the complications early. In this study, we examine markers, which are based on reversible modifications of the DNA, in the context of diabetes and its complications. We found that one of these biomarkers is able to predict the development of diabetes complications over a period of about seven years in our dataset. If these results can be confirmed in other studies, our findings might help physicians to identify patients with diabetes that have an increased risk for developing complications in the future.

Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of Weight Regain After Bariatric surgery a Retrospective Observational Study.

Weight regain after bariatric surgery occurs in up to a third of patients and reduces treatment-associated health benefits. The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) for treatment of type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains to be defined. This was a single centre retrospective observational study conducted at a Swiss bariatric reference centre. Patients with 6 months of treatment with GLP1-RA, up until November 2021, due to weight regain after bariatric surgery were identified. Data on body weight and relevant clinical parameters were collected before and after 6 months of treatment with GLP1-RA. Data are presented as median (interquartile range). Fifty patients (82% female) were included. Before GLP1-RA treatment (liraglutide, n29 semaglutide, n21), weight and BMI were 90.5 kg (83.4, 107.9) and 34.0 kgm For patients experiencing weight regain after bariatric surgery, two-thirds of the weight regain can be safely lost with GLP1-RA, providing clinicians with a therapeutic option for this clinical challenge, and highlights the need for a large-scale randomized clinical trial.

Evaluation of a Synchronous, Online Diabetes Nutrition Education Program for American Indians and Alaska Natives With Type 2 Diabetes Facilitators and Participants Experiences.

To explore the overall experiences of key players involved in a culturally adapted, online, synchronous diabetes nutrition education program across 5 reservation tribal and intertribal urban Indian clinics. A multimethods design, including postclass surveys with Likert-scale and short-answer questions, was completed after each of the 5 classes. Participants (n 54) and class facilitatorscoordinators (n 10) completed postclass surveys (n 189 and 58, respectively). A subset of participants (n 24) and all class facilitatorscoordinators (n 10) engaged in online focus groups after the conclusion of program implementation. Qualitative thematic methods and frequency distributions were used to analyze the data. Most participants reported that the classes were enjoyable (94%), culturally respectful (77%), and easily accessed online (68%). Qualitative themes included (1) class satisfaction, (2) class improvements, (3) preference for class facilitator, and (4) recommendations to improve recruitment and retention. These findings will guide program modifications to provide improved diabetes nutrition education for American Indians and Alaska Natives adults with type 2 diabetes.

GALIPDIA study Reaching lipid targets in a population with type 2 diabetes (T2DM) from the Northwest of Spain.

To assess the degree of compliance with the European ESCEAS 2016 and 2019 dyslipidaemia guidelines in patients with type 2 diabetes mellitus (T2DM). Multicentre retrospective cross-sectional study, conducted in 380 adults with T2DM and dyslipidaemia in 7 Spanish health areas. minimum follow-up of one year in Endocrinology Units, at least one visit in 2020 and a lipid profile measurement in the last 3 months. familial hypercholesterolaemia, recent hospitalisation, active oncological pathology and dialysis. According to the 2016 and 2019 guidelines the majority of patients were classified as being at very high cardiovascular risk (86.8% vs. 72.1%, respectively). LDL-c compliance was adequate in 62.1% of patients according to the 2016 guidelines and 39.7% according to the 2019 guidelines (p<0.001). Clinical conditions such as history of cardiovascular disease and therapy-related aspects (use of statins, especially high-potency statins, combination therapies and good adherence) were significantly associated with greater achievement of lipid targets. There is a discrepancy between dyslipidaemia guideline recommendations and the reality of lipid control in patients with T2DM, despite most of these patients being at very high cardiovascular risk. Strategies to optimise lipid-lowering treatments need to be implemented.

Two siblings with a rare type of maturity-onset diabetes of the young (MODY).

Maturity-onset diabetes of the young (MODY) is a type of diabetes that does not entirely fit the usually encountered type 1 or type 2 diabetes. It is a monogenic, familial and non-autoimmune diabetes among children and young adults resulting from autosomal dominant gene mutations.MODY diagnosis is confirmed by molecular genetic testing, which is costly. Therefore, it is rarely done.Nearly 1%-6% of diabetes has a monogenic cause but this is frequently misclassified as type 1 diabetes mellitus due to the lack of genetic testing. Therefore, a correct diagnosis of MODY is crucial for determining the plan of management. Furthermore, having a patient with MODY in a family indicates screening other family members. In this case report, we highlight that paediatric diabetes cases are not always type 1 or type 2 diabetes mellitus since two siblings incidentally presented with hyperglycaemia and a confirmed diagnosis of MODY type 10 was ultimately made. Moreover, their mother who was previously labelled as a case of type 1 diabetes mellitus was diagnosed later as MODY after genetic testing.

Achievement of the ESC recommendations for secondary prevention of cardiovascular risk factors in high-risk patients with type 2 diabetes A real-world national cohort analysis.

To assess compliance with European Society of Cardiology (ESC) secondary prevention recommendations in a nationwide contemporary population with diabetes mellitus (DM) and coronary artery disease. We conducted a retrospective observational study using linked health data in patients across Wales with DM undergoing percutaneous coronary intervention (2012-2017). The follow-up was for one year. We analysed the clinical characteristics, medications, target levels for HbA1c, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and blood pressure against the ESC prevention guidelines. Overall, 3478 patients with diabetes had available data at 1-year post-PCI. Only 43% had HbA1c levels <53 mmolL, but 81% had blood pressure < 14080 (current ESC targets). Prescribing frequency of the newer hypoglycaemic agents (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors) was suboptimal, with a higher rate in patients with HbA1c ≥53 mmolmol. Only 51% 27% of the patients had LDL-C levels <1.8 1.4 mmolL (2016 2019 guidelines recommendations respectively), and 55% 34% had non-HDL-C levels <2.6 2.2 mmolL (2016 2019 guidelines respectively). Of the uncontrolled LDL-C patients, 42% (2016 target) and 35% (2019 target) were prescribed high-intensity statins. Females were more likely to have LDL-C targets above the recommended level. Achievement of ESC treatment goals in this very-high risk cohort for DM and hyperlipidaemia was far from optimal, with a low prescription rate of the guidelines-recommended therapy. Target goals for hypertension were met more frequently. An up-to-date analysis reflecting the current practice against the most recent guidelines is warranted.

Exposure to novel brominated and organophosphate flame retardants and associations with type 2 diabetes in East China A case-control study.

The alternative flame retardants, novel brominated flame retardants (NBFRs) and organophosphate flame retardants (OPFRs) are ubiquitous in the environment and biota and may induce endocrine disruption effects. Associations between traditional endocrine-disrupting chemicals and type 2 diabetes have been extensively reported in epidemiological studies. However, the effects of NBFRs and OPFRs in humans have not been reported to date. This paper reports a case-control study of 344 participants aged 25-80 years from Shandong Province, East China, where potential associations between serum NBFR and OPFR concentrations and type 2 diabetes are assessed for the first time. After adjusting for covariates (i.e., age, sex, body mass index, smoking status, alcohol consumption, triglycerides, and total cholesterol), serum concentrations of pentabromotoluene, 2,3-dibromopropyl 2,4,6-tribromophenyl ether, tri-n-propyl phosphate, triphenyl phosphate, and tris (2-ethylhexyl) phosphate were significantly positively associated with type 2 diabetes. In the control group, decabromodiphenyl ethane and triphenyl phosphate were significantly positively associated with fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol. In the quantile g-computation model, significant positive mixture effect was found between the flame retardants mixtures and high-density lipoprotein cholesterol levels, and decabromodiphenyl ethane contributed the largest positive weights to the mixture effect. Overall, these findings suggest that exposure to NBFRs and OPFRs may promote type 2 diabetes.

Synthesis and biological evaluation of 2,5-disubstituted furan derivatives containing 1,3-thiazole moiety as potential α-glucosidase inhibitors.

α-Glucosidase, which is involved in the hydrolysis of carbohydrates to glucose and directly mediates blood glucose elevation, is a crucial therapeutic target for type 2 diabetes. In this work, 2,5-disubstituted furan derivatives containing 1,3-thiazole-2-amino or 1,3-thiazole-2-thiol moiety (III-01 ∼ III-30) were synthesized and screened for their inhibitory activity against α-glucosidase. α-Glucosidase inhibition assay demonstrated that all compounds had IC

ACUTE SOLUBLE FIBRE SUPPLEMENTATION HAS NO IMPACT ON REDUCING POST-PRANDIAL GLUCOSE EXCURSIONS IN ADULTS WITH CYSTIC FIBROSIS AND GLUCOSE INTOLERANCE.

Cystic fibrosis (CF)-related diabetes (CFRD) is a common comorbidity in CF. In CFRD, fasting blood glucose level is often normal, but post-prandial glycaemia (PPG) is problematic. Elevated PPG has been associated to a higher risk of developing CFRD, a worst clinical state and a lower pulmonary function. Interventional studies in type 2 diabetes have demonstrated a beneficial impact of fibre supplement on PPG. Our objective is to evaluate the efficiency of 2 doses of a soluble fibre supplement to lower PPG in CF patients with glucose intolerance (pre-diabetic or CFRD patients). This is a double-blinded crossover interventional study with three interventions placebo or psyllium fibre (5.1g or 7.7g) of soluble fibre consumed before breakfast. A second meal (lunch) is also eaten four hours later to evaluate a second meal effect. Blood glucose and insulin were measured during the interventions. In 14 adult CF patients with glucose intolerance (n 10) or CFRD (n 4), we observed no beneficial effect of fibre supplementation on PPG for both meals. However, all blood glucose levels were lower after the lunch compared to breakfast in spite of the higher carbohydrate content. An acute treatment with fibre supplementation had no effect on blood glucose control in patients with CF-IGT or CFRD.

Misexpression of LINC01410, FOSL1, and MAFB in peripheral blood mononuclear cells associated with diabetic nephropathy.

Currently, diabetic nephropathy (DN) is considered the leading cause of the end-stage renal disease (ESRD). However, its specific molecular mechanism is still unclear, and there is still a lack of effective diagnostic and therapeutic methods. A pathway was assumed after bioinformatics analysis of GEO datasets related to individuals with various levels of DN, LINC01410, MAFB, and FOSL1. Then, 46 patients with type 2 diabetes (T2DM) and different levels of albuminuria, and 12 individuals without diabetes, were selected. qPCR was performed to evaluate gene expression. One-way ANOVA followed by Tukeys -and linear trend tests were performed to analyze gene expression in different stages of the disease. Moreover, receiver operating characteristic (ROC) curves and the correlation between LINC01410, FOSL1, and MAFB were analyzed. LINC01410, MAFB, and FOSL1 were selected based on bioinformatics analyses. The qPCR results showed that the expression of LINC01410 decreased, and FOSL1 and MAFB increased in micro-and macroalbuminuria groups compared to normoalbuminuria groups (P < 0.05). ROC curves demonstrated a significant diagnostic accuracy of LINC01410, MAFB, and FOSL1 between DN and participants with normoalbuminuria (P < 0.05). Pearsons correlation analysis revealed a positive association between the expressions of FOSL1 and MAFB (p 0.01, r 0.39). However, there was no correlation between LINC01410 with MAFB and FOSL1 (p 0.23 and p 0.21, respectively). Dysregulation of LINC01410, MAFB, and FOSL1 is related to DN. These results may provide new insights into the role of LINC01410, MAFB, and FOSL1 as potential biomarkers in DN.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD) A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 16 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use robust trials are required to appropriately address efficacy and safety.

Efficacy and Tolerability of Insulin Degludec Versus Other Long-acting Basal Insulin Analogues in the Treatment of Type 1 and Type 2 Diabetes Mellitus A Systematic Review and Meta-analysis.

The goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D). Those randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A Data from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (-0.370 mmolL 95% CI, -0.473 to -0.267 mmolL P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D the differences in the risks for severe hypoglycemia were not significant. Compared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

Evaluating the nature and prevalence of glucocorticoid-induced Type 2 diabetes mellitus in patients with autoimmune bullous diseases (AIBDs).

Glucocorticoid use in patients with autoimmune bullous disease is associated with significant morbidity, and in some cases, excess mortality. The hyperglycaemic complications arising from glucocorticoid use have been well-documented and range from mild hyperglycaemia to diabetic ketoacidosis. Patients with pre-existing glucose intolerance or type 2 diabetes mellitus are at increased risk of developing complications. Several other factors have been investigated for their association with steroid-induced hyperglycaemia, including patient age, gender, family history, dose, regimen and duration of therapy. Findings in the current literature, however, are largely conflicting and evidence is limited by methodological weaknesses. Glucocorticoids should be used with caution, and steroid-using patients should be closely monitored for adverse effects.

Prevalence and description of the skin reactions associated with adhesives in diabetes technology devices in an adult population results of the CUTADIAB study.

Use of continuous glucose measurement (CGM) systems and continuous subcutaneous insulin infusion (CSII) devices adhering to the skin can lead to skin reactions. The objective was to determine the prevalence and consequences of skin reactions to CGM or CSII infusion sites in a large, unbiased population. This is a cross-sectional, multicenter study. All adult patients with diabetes seen in consultation over a period of 7 months and using or having used a system with skin adhesives in the last 10 years were included and filled out a self-assessment questionnaire. Among 851 patients, skin reaction was reported in 28% with CGM and 29% with CSII. Users reporting reactions were more frequently women for CGM and CSII, and they had type 1 more often than type 2 diabetes for CGM (p<0.001). Manifestations were similar for CGM and CSII reactions redness and pruritus in 70%-75% of patients with reactions, pain in 20%-25%, vesicles and desquamation in 12%-15%. Manifestations occurred within the first 24 hours of the first use in 22%-24% of CGM and CSII reactions, but after more than 6 months in 38% and 47% of CGM and CSII reactions, respectively. Device use was definitively stopped in 12% of patients with CGM reaction (3.2% of all users), and 7% of CSII reaction (2.1% of all users). Skin reactions were common, with similar presentations in CGM and CSII users. Manifestations suggested skin irritation rather than allergies. These reactions rarely led to the definitive discontinuation of the use of the device.

Efficacy and Safety of Ertugliflozin Added to Metformin A Pooled Population from Asia with Type 2 Diabetes and Overweight or Obesity.

The efficacy and safety of ertugliflozin have not been well characterized in Asian populations with type 2 diabetes (T2D) and overweight or obesity as defined by the Chinese Diabetes Society body mass index (BMI) ≥ 24 kgm These post hoc analyses of pooled data from two randomized, double-blind, 26-week studies assessed the efficacy and safety of ertugliflozin (5 mg or 15 mg) compared with placebo in participants from Asia with T2D and baseline BMI ≥ 24 kgm The 445 participants had a mean age of 55.5 years, T2D duration 6.6 years, glycated hemoglobin (HbA1c) 8.1%, and BMI 27.6 kgm In participants from Asia with T2D inadequately controlled by metformin monotherapy, and BMI ≥24 kgm Clinicaltrials.gov identifiers NCT02033889, NCT02630706.

Are glucose and insulin levels at all time points during OGTT a reliable marker of diabetes mellitus risk in pediatric obesity

Childhood overweight and obesity associated with insulin resistance and metabolic syndrome represent the new global pandemic and the main causative factors for dysglycemia, prediabetes, and Type 2 Diabetes Mellitus (T2DM). Predictors, such as HOMA-IR, HOMA-β%, and QUICKI lack specific reference values in children. OGTT is a gold standard for glycometabolic assessment. Recently, a glycemic level higher than 155 mgdl at 60 after glucose ingestion has been defined as a risk factor for T2DM in obese adolescents. We aim to analyze and correlate fasting insulin-resistance markers with OGTT results in overweightobese children and adolescents. We retrospectively evaluated glucose and insulin values during a 2-h OGTT every 30 min in 236 overweightobese patients. Glucose values and insulin sum during OGTT were compared to glycometabolic indexes and different cut-off values for insulin sum. A 1-h glucose > 155 mgdl and insulin sum > 535 microUml at all times during OGTT are the best predictors of diabetes risk in obese youths. A1-h glucose > 155 mgdl is significantly associated with HbA1c > 5.7%, while no association was observed between HbA1c > 5.7% and glucose levels at baseline and 2 h. The ability of the standardized HOMA-IR to predict the prediabetes status is clearly lower than the total insulin sum at OGTT. Our study demonstrates that also 1-h post-OGTT glucose, together with HbA1c, is an effective diabetes predictor.

Effects of empagliflozin on left ventricular diastolic function in addition to usual care in individuals with type 2 diabetes mellitus-results from the randomized, double-blind, placebo-controlled EmDia trial.

The sodium-glucose co-transporter 2 inhibitor empagliflozin improves cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM) and heart failure. Experimental studies suggest a direct cardiac effect of empagliflozin associated with an improvement in left ventricular diastolic function. In the randomized, double-blind, two-armed, placebo-controlled, parallel group trial EmDia, patients with T2DM and elevated left ventricular EE´ ratio were enrolled and randomized 11 to receive empagliflozin 10 mgday versus placebo. The primary endpoint was the change of left ventricular EE´ ratio after 12 weeks of intervention. A total of 144 patients with T2DM and an elevated left ventricular Ee´ ratio (age 68.9 ± 7.7 years 14.1% women Ee´ ratio 9.618.2411.14, left ventricular ejection fraction 58.9% ± 5.6%). After 12 weeks of intervention, empagliflozin resulted in a significant higher decrease in the primary endpoint Ee´ ratio by - 1.18 (95% confidence interval (CI) - 1.72- 0.65 P < 0.0001) compared with placebo. The beneficial effect of empagliflozin was consistent across all subgroups and also occurred in subjects with heart failure and preserved ejection fraction (n 30). Additional effects of empagliflozin on body weight, HbA1c, uric acid, red blood cell count, hemoglobin, mean corpuscular hemoglobin, and hematocrit were detected (all P < 0.001). Approximately one-third of the reduction in Ee´ by empagliflozin could be explained by the variables examined. Empagliflozin improves diastolic function in patients with T2DM and elevated end-diastolic pressure. Since the positive effects were consistent in patients with and without heart failure with preserved ejection fraction, the data add a mechanistic insight for the beneficial cardiovascular effect of empagliflozin. Clinicaltrials.gov, unique identifier NCT02932436.

Diabetes distress mediates the relationship between depressive symptoms and glycemic control among adults with type 2 diabetes findings from a multi-site diabetes peer support intervention.

Diabetes distress is positively associated with HbA1c and may mediate the relationship between depressive symptoms and HbA1c. This study examined these relationships in a geographically, socioeconomically, and ethnically diverse sample of adults with type 2 diabetes. Using data from five US sites evaluating peer support for diabetes management (n917), Structural Equation Modeling (SEM) examined whether diabetes distress (four items from Diabetes Distress Scale) mediated the relationship between depressive symptoms (PHQ-8) and HbA1c. Sites compared interventions of varying content and duration with control conditions. Time from Baseline Assessment to Final Assessment varied from six to 18 months. Site characteristics were controlled by entering site as a covariate along with age, sex, education, diabetes duration, insulin use, and interventioncontrol assignment. Depressive symptoms, diabetes distress, and HbA1c were all intercorrelated cross-sectionally and from Baseline to Final Assessment (rs from .10 to .57 ps<0.05). In SEM analyses, diabetes distress at Final Assessment mediated the relationship between Baseline depressive symptoms and HbA1c at Final Assessment (indirect effect b.031, p<0.001), controlling for Baseline HbA1c and covariates. Parallel analysis of whether depressive symptoms mediated the relationship between Baseline diabetes distress and HbA1c at Final Assessment was not significant. In this diverse sample, diabetes distress mediated the influence of depressive symptoms on HbA1c but the reverse, depressive symptoms mediating the effect of distress, was not found. These findings add to the evidence that diabetes distress is a worthy intervention target to improve clinical status and quality of life among individuals with type 2 diabetes.

Associations between oral processing, saliva, and bolus properties on daily glucose excursions amongst people at risk of type-2 diabetes.

Not Available.

Diabetes and hyperglycaemia are frequent diagnoses in the hospital, and in-hospital hyperglycaemia is associated with adverse clinical outcomes. Insulin is the preferred treatment for in-hospital hyperglycaemia. This review summarises the management of hyperglycaemia in Danish hospitals. In Denmark, sliding-scale insulin is often applied with the addition of basal insulin after 1-2 days with hyperglycaemia which differs from international guidelines recommending a basal-bolus regimen. The optimal non-intensive care unit glucose targets, the safety and efficacy level of non-insulin antidiabetic agents, and continuous glucose monitoring are subjects of further research.

The effect of mindfulness-based stress reduction (MBSR) training on serum cortisol levels, depression, stress, and anxiety in type 2 diabetic older adults during the COVID-19 outbreak.

Old age is rapidly increasing and is linked to with chronic diseases, especially diabetes. Diabetes is associated with increased anxiety, stress, and depression and, in turn, can increase cortisol secretion. To this end, the present research studied the impact of mindfulness-based stress reduction (MBSR) training on serum cortisol levels, depression, anxiety, and stress in type 2 diabetic (T2DM) older adults during the COVID-19 epidemic. The participants in this interventional work were 56 older adult patients with type 2 diabetes chosen through systematic random sampling and then randomly divided into control and intervention groups containing equal members. In the intervention group, the participants attended eight mindfulness-based stress reduction (MBSR) training sessions. The subjects in the control group received no intervention. Since four patients left the study, only data for 52 patients were collected using the Depression Anxiety Stress Scale (DASS-21) and a demographic and disease information questionnaire. Data were examined with SPSS18 software using the Kolmogorov-Smirnov test, chi-square test, Fisher test, independent samples t-test, and two-way ANOVA the significance was p<0.05. Statistically significant differences were observed between the mean scores of anxiety, stress, depression, and cortisol levels in the intervention group (p<0.00001) before, directly after, and three months after the intervention. However, no statistically significant difference was observed in the mentioned variables in the control group. The mindfulness-based stress reduction (MBSR) intervention can improve anxiety, depression, stress, and cortisol levels in older adults suffering from T2DM.

The ketogenic diet its impact on human gut microbiota and potential consequent health outcomes a systematic literature review.

This systematic review examined the diets impact on the human gut microbiota to identify potential consequent health outcomes. The extreme macronutrient profile of the ketogenic diet (KD) instigates compositional shifts in the guts microbial community. In this systematic literature review, an evidence-based and methodical approach was undertaken, which involved systematic searches of the Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, generating a total of 263 relevant research papers. Following the application of inclusion and exclusion criteria, eight papers were deemed suitable for inclusion. These papers were critically appraised using a checklist tool adapted from the National Institute of Care and Excellence (NICE). The findings were analysed using a simplified thematic analysis. The results provide strong evidence for a persistent reduction in Changes to microbial communities resulting from KD adherence are potentially detrimental to colonic health. The persistent reduction in