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A Nudge-Inspired AI-Driven Health Platform for Self-Management of Diabetes.

Diabetes mellitus is a serious chronic disease that affects the blood sugar levels in individuals, with current predictions estimating that nearly 578 million people will be affected by diabetes by 2030. Patients with type II diabetes usually follow a self-management regime as directed by a clinician to help regulate their blood glucose levels. Today, various technology solutions exist to support self-management however, these solutions tend to be independently built, with little to no research or clinical grounding, which has resulted in poor uptake. In this paper, we propose, develop, and implement a nudge-inspired artificial intelligence (AI)-driven health platform for self-management of diabetes. The proposed platform has been co-designed with patients and clinicians, using the adapted 4-cycle design science research methodology (A4C-DSRM) model. The platform includes (

Pharmacokinetic-Pharmacometabolomic Approach in Early-Phase Clinical Trials A Way Forward for Targeted Therapy in Type 2 Diabetes.

Pharmacometabolomics in early phase clinical trials demonstrate the metabolic profiles of a subject responding to a drug treatment in a controlled environment, whereas pharmacokinetics measure the drug plasma concentration in human circulation. Application of the personalized peak plasma concentration from pharmacokinetics in pharmacometabolomic studies provides insights into drugs pharmacological effects through dysregulation of metabolic pathways or pharmacodynamic biomarkers. This proof-of-concept study integrates personalized pharmacokinetic and pharmacometabolomic approaches to determine the predictive pharmacodynamic response of human metabolic pathways for type 2 diabetes. In this study, we use metformin as a model drug. Metformin is a first-line glucose-lowering agent however, the variation of metabolites that potentially affect the efficacy and safety profile remains inconclusive. Seventeen healthy subjects were given a single dose of 1000 mg of metformin under fasting conditions. Fifteen sampling time-points were collected and analyzed using the validated bioanalytical LCMS method for metformin quantification in plasma. The individualized peak-concentration plasma samples determined from the pharmacokinetic parameters calculated using Matlab Simbiology were further analyzed with pre-dose plasma samples using an untargeted metabolomic approach. Pharmacometabolomic data processing and statistical analysis were performed using MetaboAnalyst with a functional meta-analysis peaks-to-pathway approach to identify dysregulated human metabolic pathways. The validated metformin calibration ranged from 80.4 to 2010 ngmL for accuracy, precision, stability and others. The median and IQR for Cmax was 1248 (849-1391) ngmL AUC

Two-Layer Sustained-Release Microneedles Encapsulating Exenatide for Type 2 Diabetes Treatment.

Daily administration of multiple injections can cause inconvenience and reduce compliance in diabetic patients thus, microneedle (MN) administration is favored due to its various advantages. Accordingly, the two-layer sustained-release MNs (TS-MNs) were fabricated by encapsulating exenatide (EXT) in calcium alginate (CA) gel in this work. The TS-MNs were composed of a sodium alginate (SA) tip and a water-soluble matrix-containing calcium chloride (CaCl

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective.

Discrepancy between the Actions of Glucagon-like Peptide-1 Receptor Ligands in the Protection of the Heart against Ischemia Reperfusion Injury.

Tirzepatide is a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and a promising therapy for type 2 diabetes mellitus (T2DM). GLP-1 is an incretin hormone with therapeutic potential beyond type 2 diabetes mellitus. However, GLP-1 is rapidly degraded by dipeptdyl peptidase-IV (DPP-IV) to GLP-1 (9-36). Exendin-4 (Ex-4) is a DPP-IV-resistant GLP-1 receptor agonist which, when truncated to Ex-4 (9-39), acts as a GLP-1 receptor antagonist. In the present study, hearts isolated from Wistar rats (

European Safety Analysis of mRNA and Viral Vector COVID-19 Vaccines on Glucose Metabolism Events.

Few data have been published on the effects of impaired glucose metabolism induced by COVID-19 vaccines. We decided to perform a study to describe Individual Case Safety Reports (ICSRs) of impaired glucose metabolism events reported in the European database (Eudravigilance, EV). ICSRs were retrieved from the online website of Eudravigilance. The reporting odds ratios (ROR) were computed to assess the reporting frequency for COVID-19 mRNA vaccines compared to COVID-19 viral vector-based vaccines. A total of 3917 ICSRs with a COVID-19 vaccine suspected were retrieved, with a total of 4275 impaired glucose metabolism events. Overall, the most reported events were related to high glucose levels (2012 47.06%). The mRNA vaccines were associated with an increased reporting frequency of type 1 diabetes mellitus (ROR 1.86 95% CI 1.33-2.60), type 2 diabetes mellitus (ROR 1.58 95% CI 1.03-2.42), high glucose levels (ROR 1.16 95% CI 1.06-1.27), diabetes mellitus inadequate control (ROR 1.63 95% CI 1.25-2.11), and hypoglycemia (ROR 1.62 95% CI 1.41-1.86) compared to viral vector-based vaccines. mRNA COVID-19 vaccines were associated with an increased reporting frequency of alterations of glucose homeostasis compared to viral-vector COVID-19 vaccines. Clinicians should be aware of these events to better manage glycemic perturbations. Larger nationwide studies are warranted to verify these findings.

Microbiological, Clinical and Radiological Aspects of Diabetic Foot Ulcers Infected with Methicillin-Resistant and -Sensitive

Diabetic foot ulcer (DFU) is one of the most common chronic complications of diabetes. This study aimed to assess the factors with an impact on the infection of diabetic foot ulcers by methicillin-resistant

Early and Strong Leptin Reduction Is Predictive for Long-Term Weight Loss during High-Protein, Low-Glycaemic Meal Replacement-A Subanalysis of the Randomised-Controlled ACOORH Trial.

Lifestyle interventions including meal replacement are suitable for prevention and treatment of obesity and type-2-diabetes. Since leptin is involved in weight regulation, we hypothesised that a meal replacement-based lifestyle intervention would reduce leptin levels more effectively than lifestyle intervention alone. In the international, multicentre, randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related- Health-Risk), overweight or obese participants with metabolic syndrome criteria (

The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant

Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease.

The mechanisms connecting obesity with type 2 diabetes, insulin resistance, nonalcoholic fatty liver disease, and cardiovascular diseases remain incompletely understood. The function of MAPK phosphatase-2 (MKP-2), a type 1 dual-specific phosphatase (DUSP) in whole-body metabolism, and how this contributes to the development of diet-induced obesity, type 2 diabetes (T2D), and insulin resistance is largely unknown. We investigated the physiological contribution of MKP-2 in whole-body metabolism and whether MKP-2 is altered in obesity and human fatty liver disease using MKP-2 knockout mice models and human liver tissue derived from fatty liver disease patients. We demonstrate that, for the first time, MKP-2 expression was upregulated in liver tissue in humans with obesity and fatty liver disease and in insulin-responsive tissues in mice with obesity. MKP-2-deficient mice have enhanced p38 MAPK, JNK, and ERK activities in insulin-responsive tissues compared with wild-type mice. MKP-2 deficiency in mice protects against diet-induced obesity and hepatic steatosis and was accompanied by improved glucose homeostasis and insulin sensitivity.

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders.

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.

Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes A 26-Week Prospective Real-Life Study.

Body weight (BW) loss is an essential therapeutic goal in type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists are effective in reducing BW, but their effect on body composition has not yet been fully explored. The study aim was to assess the impact of Semaglutide on body composition in patients with T2D. Forty patients with T2D were treated with subcutaneous Semaglutide and evaluated at the baseline (T0) and after three (T3) and six (T6) months. Body composition was assessed by a phase-sensitive bioimpedance analyzer. Visceral adipose tissue (VAT) thickness was also measured with an ultrasonographic method (US-VAT). Anthropometric variables, muscular strength, and laboratory tests were analyzed and compared. A significant decrease in VAT, the fat mass index (FMI), and BW loss was observed at all observation times. US-VAT, the skeletal mass index (SMI), the fat-free mass index (FFMI), waist circumferences, and glycated hemoglobin had lessened after three months and remained stable at T6. No variations in muscle strength, the muscle quality index, and body water were found. In a real-life setting, Semaglutide provided significant weight loss mainly due to a reduction in the FMI and VAT, with non-clinically relevant changes in the SMI, the FFMI, and muscle strength. Most importantly, the results were obtained after three months of treatment and persisted thereafter.

The Efficacy of Ginseng (Panax) on Human Prediabetes and Type 2 Diabetes Mellitus A Systematic Review and Meta-Analysis.

Results from different clinical trials on the effects of ginseng on prediabetes and type 2 diabetes (T2DM) are still inconsistent. To fill this knowledge gap, we investigated the overall effects of ginseng supplementation on improving cardiometabolic biomarkers among these patients. A systematic literature search was conducted on PubMedMEDLINE, Scopus, Web of Science, and Cochrane library. A random-effect model was applied to estimate the weighted mean difference and 95% CI for each outcome. Overall, 20 eligible RCTs were included. Meta-analyses revealed that ginseng supplementation significantly reduced serum concentration of FPG, TC, IL-6, and HOMA-IR values. It also increased HR and TNF-α levels. Ginseng supplementation changed HOMA-IR and HDL-C significantly based on dose and changed HOMA-IR and LDL-C significantly based on study duration in a non-linear fashion. Furthermore, meta-regression analyses indicated a linear relationship between ginseng dose and absolute changes in HDL-C. Moreover, subgroup analyses showed that ginseng supplementation changed TC and LDL-C when the supplementation dose was ≥2 gday. Our findings suggest that ginseng supplementation may be an effective strategy for improving cardiometabolic profiles in individuals with prediabetes and T2DM.

Very Low-Calorie Ketogenic Diet A Potential Application in the Treatment of Hypercortisolism Comorbidities.

A very low-calorie ketogenic diet (VLCKD) is characterized by low daily caloric intake (less than 800 kcalday), low carbohydrate intake (lt50 gday) and normoproteic (1-1.5 g of proteinkg of ideal body weight) contents. It induces a significant weight loss and an improvement in lipid parameters, blood pressure, glycaemic indices and insulin sensitivity in patients with obesity and type 2 diabetes mellitus. Cushings syndrome (CS) is characterized by an endogenous or exogenous excess of glucocorticoids and shows many comorbidities including cardiovascular disease, obesity, type 2 diabetes mellitus and lipid disorders. The aim of this speculative review is to provide an overview on nutrition in hypercortisolism and analyse the potential use of a VLCKD for the treatment of CS comorbidities, analysing the molecular mechanisms of ketogenesis.

Relationship between Ultra-Processed Food Consumption and Risk of Diabetes Mellitus A Mini-Review.

Studying the factors that cause diabetes and conducting clinical trials has become a priority, particularly raising awareness of the dangers of the disease and how to overcome it. Diet habits are one of the most important risks that must be understood and carefully applied to reduce the risk of diabetes. Nowadays, consuming enough home-cooked food has become a challenge, particularly with modern life performance, pushing people to use processed foods. Ultra-processed food (UPF) consumption has grown dramatically over the last few decades worldwide. This growth is accompanied by the increasing prevalence of non-communicable diseases (NCDs) such as cardiovascular diseases, hypertension, and type 2 diabetes. UPFs represent three main health concerns (i) they are generally high in non-nutritive compounds such as sugars, sodium, and

Metabolic Dysfunction-Associated Fatty Liver Disease Is Associated with the Risk of Incident Cardiovascular Disease A Prospective Cohort Study in Xinjiang.

In 2020, a group of international experts proposed a new term metabolic dysfunction-associated fatty liver disease (MAFLD) to replace non-alcoholic fatty liver disease. This study aimed to describe the epidemic characteristics of MAFLD, incidence of cardiovascular disease (CVD), and relationship between MAFLD and incident CVD. In 2016, 12,794 Uyghur adults from Kashgar, Xinjiang, were grouped according to the presence or absence of MAFLD. The primary outcome was the occurrence of CVD events. Fatty liver was diagnosed using ultrasound. The prevalence of MAFLD was 16.55%. After excluding patients with previous CVD, 11,444 participants were followed up for a median period of 4.7 years. During the follow-up period, the overall CVD incidence was 10.40% (119011,444). The incidence of CVD in the patients with MAFLD was significantly higher than that in the non-MAFLD patients (18.38% vs. 9.02%,

Physicochemical Characteristics and Antidiabetic Properties of the Polysaccharides from

This study aimed to investigate the

Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine Current and Future Trends.

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimers disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.

Short-Term Treatment with Empagliflozin Resulted in Dehydration and Cardiac Arrest in an Elderly Patient with Specific Complications A Case Report and Literature Review.

Empagliflozin is a sodium-glucose cotransporter-2 inhibitor widely used in the treatment of diabetes mellitus and heart failure. Our case study involved a 68-year-old patient who was admitted to the hospital because of a cerebral infarction. The patient was simultaneously diagnosed with diabetes mellitus and heart failure, for which empagliflozin was initiated. However, food and fluid intake were reduced due to poor appetite. In addition to the side effects of empagliflozin, the patient developed severe dehydration and cardiac arrest. Careful assessment of dehydration and preventive water intake is recommended in elderly patients and those with neurological deficits, especially when receiving empagliflozin.

In Vitro and In Ovo Evaluation of the Potential Hepatoprotective Effect of Metformin.

Predicting the Risk of Incident Type 2 Diabetes Mellitus in Chinese Elderly Using Machine Learning Techniques.

Early identification of individuals at high risk of diabetes is crucial for implementing early intervention strategies. However, algorithms specific to elderly Chinese adults are lacking. The aim of this study is to build effective prediction models based on machine learning (ML) for the risk of type 2 diabetes mellitus (T2DM) in Chinese elderly. A retrospective cohort study was conducted using the health screening data of adults older than 65 years in Wuhan, China from 2018 to 2020. With a strict data filtration, 127,031 records from the eligible participants were utilized. Overall, 8298 participants were diagnosed with incident T2DM during the 2-year follow-up (2019-2020). The dataset was randomly split into training set (

Glucose Metabolism Derangements and Thyroid Nodules Does Sex Matter

(1) Background Glucose metabolism derangements (GMD) and thyroid nodules (TNs) are the most frequent endocrine disorders, and their relationship is still controversial little evidence is reported regarding sex differences. We aim to evaluate the association between GMDs and TNs according to sex and the sex differences in glucose metabolism and insulin sensitivity (IS). (2) Methods We evaluated 342 patients (268 females and 74 males) at high GMD risk undergoing an oral glucose tolerance test and a thyroid ultrasound. (3) Results The TN prevalence was 61% (

Endocrine and Metabolic Illnesses in Young Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by an insatiable appetite that leads to morbid obesity. Previous studies reported health problems in adults with PWS. However, studies on younger adults are lacking, and there are no specific studies of endocrine and metabolic illness in this age group. We performed a retrospective cohort study of 68 individuals with PWS aged 19 to 34 years at Samsung Medical Center. The prevalence of endocrine and metabolic illnesses were compared with those in an age-, sex-, and BMI-matched healthy control group. Young adults with PWS had a higher prevalence of metabolic syndrome (35.3% vs. 4.4%), type 2 diabetes mellitus (50.0% vs. 5.4%), hypertension (30.8% vs. 16.1%), dyslipidemia (38.2% vs. 14.7%), decreased bone density (26.4% vs. 0.9%), and sleep apnea (32.3% vs. 4.4%) than controls (all

Impulsive Personality Traits Predicted Weight Loss in Individuals with Type 2 Diabetes after 3 Years of Lifestyle Interventions.

Impulsivity has been associated with type 2 diabetes (T2D) and may negatively impact its management. This study aimed to investigate impulsive personality traits in an older adult population with T2D and their predicting role in long-term weight control and glycemic management, through glycated hemoglobin (HbA

Electrodiagnostic Testing and Nerve Ultrasound of the Carpal Tunnel in Patients with Type 2 Diabetes.

In diabetic patients, controversies still exist about the validity of electrodiagnostic and nerve ultrasound diagnosis for carpal tunnel syndrome (CTS). We analyzed 69 patients with type 2 diabetes. Nerve conduction studies and peripheral nerve ultrasound of the median nerve over the carpal tunnel were performed. CTS symptoms were assessed using the Boston Carpal Tunnel Questionnaire. Polyneuropathy was assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Although 19 patients reported predominantly mild CTS symptoms, 37 patients met the electrophysiological diagnosis criteria for CTS, and six patients were classified as severe or extremely severe. The sonographic cross-sectional area (CSA) of the median nerve at the wrist was larger than 12 mm

When Sugar Reaches the Liver Phenotypes of Patients with Diabetes and NAFLD.

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.

Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern.

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid

The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications A Narrative Review.

Kisspeptins are the family of neuropeptide products of the

Effect of Anti-Osteoporotic Treatments on Circulating and Bone MicroRNA Patterns in Osteopenic ZDF Rats.

Bone fragility is an adverse outcome of type 2 diabetes mellitus (T2DM). The underlying molecular mechanisms have, however, remained largely unknown. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression in health and disease states. The aim of this study was to investigate the genome-wide regulation of miRNAs in T2DM bone disease by analyzing serum and bone tissue samples from a well-established rat model of T2DM, the Zucker Diabetic Fatty (ZDF) model. We performed small RNA-sequencing analysis to detect dysregulated miRNAs in the serum and ulna bone of the ZDF model under placebo and also under anti-sclerostin, PTH, and insulin treatments. The dysregulated circulating miRNAs were investigated for their cell-type enrichment to identify putative donor cells and were used to construct gene target networks. Our results show that unique sets of miRNAs are dysregulated in the serum (

Hypertension and Type 2 Diabetes-The Novel Treatment Possibilities.

Elevated blood pressure and hyperglycaemia frequently coexist and are both components of metabolic syndrome. Enhanced cardiovascular risk is strongly associated with diabetes and the occurrence of hypertension. Both hypertension and type 2 diabetes, if treated inappropriately, lead to serious complications, increasing the mortality of patients and generating much higher costs of health systems. This is why it is of great importance to find the missing link between hypertension and diabetes development and to simultaneously search for drugs influencing these two disorders or even drugs aimed at their pathological bases. Standard antihypertensive therapy mainly focuses on blood pressure reduction, while novel drugs also possess a wide range of pleiotropic modes of actions, such as cardio- and nephroprotective properties or body weight reduction. These properties are especially desirable in a situation when type 2 diabetes coexists with hypertension. This review describes the connections between diabetes and hypertension development and briefly summarises the current knowledge regarding attempts to define targets for the treatment of high blood pressure in diabetic patients. It also describes the standard hypotensive drugs preferred in patients with type 2 diabetes, as well as novel drugs, such as finerenone, esaxerenone, sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 analogues and sacubitrilvalsartan.

Influence of Insulin Receptor Single Nucleotide Polymorphisms on Glycaemic Control and Formation of Anti-Insulin Antibodies in Diabetes Mellitus.

Single nucleotide polymorphisms (SNPs) in insulin and insulin receptor genes may influence the interaction between the two molecules, as may anti-insulin antibodies (IAs), commonly found in patients with type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D) treated with exogenous insulin. We examined the impact of two SNPs in the human insulin gene (

How Diabetes and Other Comorbidities of Elderly Patients and Their Treatment Influence Levels of Glycation Products.

Medical care for geriatric patients is a great challenge, mainly due to various overlapping deficits relevant to numerous coexisting diseases, of which the most common are diabetes mellitus and atherosclerosis. In the case of diabetes, the glycation process is intensified, which accelerates atherosclerosis development and diabetic complications. Our goal was to investigate the relationship between the classical biochemical parameters of diabetes and atherosclerosis, as well as parameters which may indicate a nephropathy, and the parameters strictly related to glycation, taking into account the pharmacological treatment of patients. Methods We analyzed the patients serum concentrations of fluorescent glycation product-pentosidine, concentrations of soluble receptors for advanced glycation products (sRAGE), lipoprotein receptor-1 (LOX-1), galectin 3 (GAL3), scavenger receptor class A (SR-A), and scavenger receptor class B (SR-BI), as well as the level of lipid peroxidation and free amine content. Among the identified correlations, the most interesting are the following sRAGE with triglycerides (r 0.47,

Medication Knowledge and Adherence in Type 2 Diabetes Mellitus Patients in Brunei Darussalam A Pioneer Study in Brunei Darussalam.

The present study measured the medication knowledge and medication adherence in patients with type 2 diabetes in Brunei Darussalam. Demographic details and diabetes knowledge were also evaluated. A cross-sectional study conducted via the administration of a structured questionnaire consisting of 4 sections via a face-to-face interview. A total of 118 participants were interviewed. A majority of the participants were aged 40 years or above (106, 89.8%). The mean number of total medications that the participants were taking was 7.36 ± 2.87 and the mean number of antidiabetic medications was 2.39 ± 1.06. As for the antidiabetic therapy, the largest proportion of the participants were taking oral antidiabetic medications only (87, 73.73%). In the diabetes knowledge section of the questionnaire, more than half of the participants (63, 53.34%) scored higher than the acquired mean score. Family history, education level, and total medications taken were significantly correlated with diabetes knowledge. However, in the medication knowledge section of the questionnaire, the mean score (3.37 ± 1.38) was below the intended score for good knowledge. Medication knowledge has been significantly associated with gender, family history and total medications taken. A majority of the participants reported non-adherence (74, 62.71%) due to various reasons. In this study, those of the Malay race were significantly correlated with adherence to their medication regimen. This study also revealed that there is no significant relationship between diabetes knowledge, medication knowledge and medication adherence. The present study provides insights in regard to patients with type 2 diabetes in Brunei Darussalam and their knowledge towards the disease as well as their medications. Despite the lack of significance between the variables, the rate of non-adherence is still alarming. Further studies are required to better understand the barriers to non-adherence in these patients.

Acute Effects of High-Intensity Interval Training on Diabetes Mellitus A Systematic Review.

This study evaluated the scientific evidence on the acute effects of high-intensity interval training (HIIT) on biochemical, cardiovascular, and metabolic parameters in patients with diabetes mellitus. The research took place using two databases (PubMed and Google Scholar) with eligible studies conducted between 2010 and 2020, using the following keywords (1) high-intensity trainingexercise (2) interval trainingexercise (3) HIITexercise AND diabetes. Data extraction was then performed on the eligible studies through content analysis using the categories author and year of publication sample characteristics methods and data collected intervention protocol and results found. Methodological quality was assessed using the PEDro scale. Fourteen studies were included, evaluating 168 people with diabetes (12246 type 21) and 42 normoglycemic individuals, which evaluated markers such as capillary and fasting blood glucose, 24-h blood glucose profile, postprandial blood glucose, incidence, and prevalence of hyperglycemia, vascular function and pressure response and control of inflammatory markers. Physical exercise was found to have several acute beneficial effects on the health of the diabetic population, such as reduced capillary and postprandial blood glucose, blood glucose profile, and blood pressure. Moreover, HIIT seems to be a safe and effective alternative in glycemic control and associated factors, superior to continuous moderate-intensity training.

Usability Evaluation and Classification of mHealth Applications for Type 2 Diabetes Mellitus Using MARS and ID3 Algorithm.

The rapid growth of mHealth applications for Type 2 Diabetes Mellitus (T2DM) patients self-management has motivated the evaluation of these applications from both the usability and user point of view. The objective of this study was to identify mHealth applications that focus on T2DM from the Android store and rate them from the usability perspective using the MARS tool. Additionally, a classification of these mHealth applications was conducted using the ID3 algorithm to identify the most preferred application. The usability of the applications was assessed by two experts using MARS. A total of 11 mHealth applications were identified from the initial search, which fulfilled our inclusion criteria. The usability of the applications was rated using the MARS scale, from 1 (inadequate) to 5 (excellent). The Functionality (3.23) and Aesthetics (3.22) attributes had the highest score, whereas Information (3.1) had the lowest score. Among the 11 applications, mySugr had the highest average MARS score for both Application Quality (4.15) as well as Application Subjective Quality (4.55). Moreover, from the classification conducted using the ID3 algorithm, it was observed that 6 out of 11 mHealth applications were preferred for the self-management of T2DM.

A Comparative Study of Natural Language Processing Algorithms Based on Cities Changing Diabetes Vulnerability Data.

(1) Background Poor adherence to management behaviors in Chinese Type 2 diabetes mellitus (T2DM) patients leads to an uncontrolled prognosis of diabetes, which results in significant economic costs for China. It is imperative to quickly locate vulnerability factors in the management behavior of patients with T2DM. (2) Methods In this study, a thematic analysis of the collected interview materials was conducted to construct the themes of T2DM management vulnerability. We explored the applicability of the pre-trained models based on the evaluation metrics in text classification. (3) Results We constructed 12 themes of vulnerability related to the health and well-being of people with T2DM in Tianjin. We considered that Bidirectional Encoder Representation from Transformers (BERT) performed better in this Natural Language Processing (NLP) task with a shorter completion time. With the splitting ratio of 631 and batch size of 64 for BERT, the test accuracy was 97.71%, the completion time was 10 min 24 s, and the macro-F1 score was 0.9752. (4) Conclusions Our results proved the applicability of NLP techniques in this specific Chinese-language medical environment. We filled the knowledge gap in the application of NLP technologies in diabetes management. Our study provided strong support for using NLP techniques to rapidly locate vulnerability factors in T2DM management.

Utilising a Real-Time Continuous Glucose Monitor as Part of a Low Glycaemic Index and Load Diet and Determining Its Effect on Improving Dietary Intake, Body Composition and Metabolic Parameters of Overweight and Obese Young Adults A Randomised Controlled Trial.

A randomised controlled trial to measure the effects of integrating real-time continuous glucose monitor (rtCGM) into a low glycaemic index (GI) and glycaemic load (GL) dietary intervention on dietary intake, body composition and specific metabolic parameters was carried out. A total of 40 overweight young adults (means ± SD) age 26.4 ± 5.3 years, BMI 29.4 ± 4.7 kgm

The Effect of Polyphenol Extract from Rosa Roxburghii Fruit on Plasma Metabolome and Gut Microbiota in Type 2 Diabetic Mice.

Rosa roxburghii fruit is an underutilized functional food abundant in polyphenols. Polyphenols have been proved to have antidiabetic effects. This study investigates the effects of Rosa roxburghii fruit polyphenols extract (RPE) on plasma metabolites and gut microbiota composition in streptozotocin (STZ)- and high-fat diet- induced type 2 diabetes using metabolomics and 16S rRNA gene sequencing. The induced diabetic mice were fed with 400 mgkg body weight RPE for 8 weeks. RPE demonstrated hypoglycemic, hypolipidemic, and anti-inflammatory effects. Colonic oxidative stress biomarkers were also lowered by RPE. Besides, RPE decreased plasma ceramides and tyrosine levels and increased carnitine and phosphatidylinositols levels, indicating improved insulin resistance, lipid metabolism, and immune response. Furthermore, RPE decreased abundances of

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity.

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (

Enhancing Night and Day Circadian Contrast through Sleep Education in Prediabetes and Type 2 Diabetes Mellitus A Randomized Controlled Trial.

Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. To determine the effect of an educational intervention delivered by primary care nurses to improve sleep hygiene, a parallel, open-label clinical trial in subjects aged 18 and older with impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) was performed. Study variables were sex, age, fasting glucose, glycated haemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, body mass index, antidiabetic treatment, diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. The intervention aimed to develop skills to improve sleep through nine simple tips. An analysis of covariance was performed on all the mean centred outcome variables controlling for the respective baseline scores. In the intervention group, PSQI dropped, the duration and quality of sleep increased, and a decrease in fasting glucose and in HbA1c levels was observed. The proposed intervention is effective for improving sleep quality, length and efficiency, and for decreasing fasting glucose and HbA1c levels in only 3 months. These findings support the importance of sleep and circadian rhythm education focused on improving IFG and T2DM.

In Search of the Holy Grail Toward a Unified Hypothesis on Mitochondrial Dysfunction in Age-Related Diseases.

Cardiolipin (CL) is a mitochondrial signature phospholipid that plays a pivotal role in mitochondrial dynamics, membrane structure, oxidative phosphorylation, mtDNA bioenergetics, and mitophagy. The depletion or abnormal acyl composition of CL causes mitochondrial dysfunction, which is implicated in the pathogenesis of aging and age-related disorders. However, the molecular mechanisms by which mitochondrial dysfunction causes age-related diseases remain poorly understood. Recent development in the field has identified acyl-CoAlysocardiolipin acyltransferase 1 (ALCAT1), an acyltransferase upregulated by oxidative stress, as a key enzyme that promotes mitochondrial dysfunction in age-related diseases. ALCAT1 catalyzes CL remodeling with very-long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). Enrichment of DHA renders CL highly sensitive to oxidative damage by reactive oxygen species (ROS). Oxidized CL becomes a new source of ROS in the form of lipid peroxides, leading to a vicious cycle of oxidative stress, CL depletion, and mitochondrial dysfunction. Consequently, ablation or the pharmacological inhibition of ALCAT1 have been shown to mitigate obesity, type 2 diabetes, heart failure, cardiomyopathy, fatty liver diseases, neurodegenerative diseases, and cancer. The findings suggest that age-related disorders are one disease (aging) manifested by different mitochondrion-sensitive tissues, and therefore should be treated as one disease. This review will discuss a unified hypothesis on CL remodeling by ALCAT1 as the common denominator of mitochondrial dysfunction, linking mitochondrial dysfunction to the development of age-related diseases.

Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications.

Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state by producing cytokines and chemokines that can reach other parts of the body, creating a systemic inflammatory condition. In this review, we described the recent findings on the role of neutrophils during obesity and the initiation of inflammation. In addition, we discuss the involvement of neutrophils in the generation of obesity-related complications using diabetes as a prime example.

The Benefits of Anthocyanins against Obesity-Induced Inflammation.

Obesity has become a serious public health epidemic because of its associations with chronic conditions such as type 2 diabetes mellitus, hypertension, cardiovascular disease, and cancer. Obesity triggers inflammation marked by the secretion of low-grade inflammatory cytokines including interleukin-6, C-reactive protein, and tumor necrosis factor-α, leading to a condition known as meta-inflammation. Currently, there is great interest in studying the treatment of obesity with food-derived bioactive compounds, which have low toxicity and no severe adverse events compared with pharmacotherapeutic agents. Here, we reviewed the beneficial effects of the bioactive compounds known as anthocyanins on obesity-induced inflammation. Foods rich in anthocyanins include tart cherries, red raspberries, black soybeans, blueberries, sweet cherries, strawberries and Queen Garnet plums. These anthocyanin-rich foods have been evaluated in cell culture, animal, and clinical studies, and found to be beneficial for health, reportedly reducing inflammatory markers. One factor in the development of obesity-related inflammation may be dysbiosis of the gut microbiome. Therefore, we focused this review on the in vitro and in vivo effects of anthocyanins on inflammation and the gut microbiota in obesity.

Overcoming the Limitations of Stem Cell-Derived Beta Cells.

Great advances in type 1 diabetes (T1D) and type 2 diabetes (T2D) treatment have been made to this day. However, modern diabetes therapy based on insulin injections and cadaveric islets transplantation has many disadvantages. That is why researchers are developing new methods to regenerate the pancreatic hormone-producing cells in vitro. The most promising approach is the generation of stem cell-derived beta cells that could provide an unlimited source of insulin-secreting cells. Recent studies provide methods to produce beta-like cell clusters that display glucose-stimulated insulin secretion-one of the key characteristics of the beta cell. However, in comparison with native beta cells, stem cell-derived beta cells do not undergo full functional maturation. In this paper we review the development and current state of various protocols, consider advantages, and propose ways to improve them. We examine molecular pathways, epigenetic modifications, intracellular components, and the microenvironment as a possible leverage to promote beta cell functional maturation. A possibility to create islet organoids from stem cell-derived components, as well as their encapsulation and further transplantation, is also examined. We try to combine modern research on beta cells and their crosstalk to create a holistic overview of developing insulin-secreting systems.

The Translational Regulation in mTOR Pathway.

The mechanisticmammalian target of rapamycin (mTOR) plays a master role in cell proliferation and growth in response to insulin, amino acids, energy levels, and oxygen. mTOR can coordinate upstream signals with downstream effectors, including transcriptional and translational apparatuses to regulate fundamental cellular processes such as energy utilization, protein synthesis, autophagy, cell growth, and proliferation. Of the above, protein synthesis is highly energy-consuming thus, mRNA translation is under the tight and immediate control of mTOR signaling. The translational regulation driven by mTOR signaling mainly relies on eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP), ribosomal protein S6 kinase (S6K), and its downstream players, which are significant in rapid cellular response to environmental change. mTOR signaling not only controls the general mRNA translation, but preferential mRNA translation as well. This means that mTOR signaling shows the stronger selectivity to particular target mRNAs. Some evidence has supported the contribution of 4E-BP and La-related proteins 1 (LARP1) to such translational regulation. In this review, we summarize the mTOR pathway and mainly focus on mTOR-mediated mRNA translational regulation. We introduce the major components of mTOR signaling and their functions in translational control in a general or particular manner, and describe how the specificity of regulation is coordinated. Furthermore, we summarize recent research progress and propose additional ideas for reference. Because the mTOR pathway is on the center of cell growth and metabolism, comprehensively understanding this pathway will contribute to the therapy of related diseases, including cancers, type 2 diabetes, obesity, and neurodegeneration.

Prospective Risk of Type 2 Diabetes in Normal Weight Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is associated with obesity and increased risk for type 2 diabetes (T2D). However, the prospective risk of T2D in normal weight women with PCOS is debated, together with the relevant prospective screening programs for T2D in normal weight women with PCOS. To review and discuss prospective risk of T2D in normal weight women with PCOS, and to give recommendations regarding prospective screening for T2D in normal weight women with PCOS. Systematic review. A systematic literature search resulted in 15 published prospective studies (10 controlled studies and 5 uncontrolled studies) regarding risk of T2D in study cohorts of PCOS, where data from normal weight women with PCOS were presented separately. In controlled studies, higher risk of T2D in normal weight women with PCOS compared to controls was reported in 410 studies, which included one study where T2D diagnosis was based on glucose measurement, two register-based studies, and one study where diagnosis of T2D was self-reported. Six of the 10 controlled studies reported no increased risk of T2D in normal weight women with PCOS. Four of these studies based the diagnosis of T2D on biochemical measurements, which supported the risk of surveillance bias in PCOS. In uncontrolled studies, 25 reported a higher risk of T2D in lean women with PCOS compared to the general population. We discuss the evidence for insulin resistance and β-cell dysfunction in normal weight women with PCOS, and aggravation in the hyperandrogenic phenotype, ageing women, and women with Asian ethnicity. Impaired glucose tolerance could be an important metabolic and vascular risk marker in PCOS. The risk of T2D may be increased in some normal weight women with PCOS. Individual risk markers such as hyperandrogenism, age gt40 years, Asian ethnicity, and weight gain should determine prospective screening programs in normal weight women with PCOS.

Tumor Necrosis Factor Receptor Superfamily Member 21 Induces Endothelial-Mesenchymal Transition in Coronary Artery Endothelium of Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is an increasing threat to human health and regarded as an important public issue. Coronary artery disease is one of the main causes of death in type 2 DM patients. However, the effect of hyperglycemia on coronary artery endothelial cells (CAECs) and the pathophysiologic mechanisms are still not well-explored. This study aims to explore the signal pathway and novel biomarkers of injury of CAECs in DM in understanding the microenvironment changes and mechanisms of diabetic heart disease. Next-generation sequence (NGS) and bioinformatics analysis to analyze the CAECs of one type 2 DM patient and one normal individual was performed, and it was found that tumor necrosis factor receptor superfamily member 21 (TNFRSF21) was a soluble factor in circulating system. Further experiments confirmed that advanced glycation end products (AGEs), the metabolite derived by hyperglycemia, increased the expression of TNFRSF21 in CAECs. TNFRSF21 induced endothelial-mesenchymal transition (EndoMT) in CAECs, resulting in increased permeability of CAECs. In addition, levels of serum TNFRSF21 were higher in type 2 DM patients with left ventricular hypertrophy (LVH) than those without LVH. Serum TNFRSF21 levels were also positively correlated with the LV mass index and negatively with LV systolic function. Serum TNFRSF21 levels were associated with changes in cardiac structure and function in patients with type 2 DM. In conclusion, TNFRSF21 plays a pathogenic role in heart disease of type 2 DM, and can be used as a biomarker of the impairment of cardiac structure and function in type 2 DM patients.

Combined Effects of Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease on the Risk of Cardiovascular Disease in Patients with Diabetes.

We investigated the combined effect of chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) on the risk of cardiovascular disease (CVD) in patients with type 2 diabetes. Data were obtained from the Korean National Health Insurance Service. Patients with diabetes who participated in health screenings from 2009 to 2011 were included. The fatty liver index (FLI) was used as a surrogate marker for NAFLD. During a mean follow-up of 6.9 years, 40,863 incidents of myocardial infarction (MI), 58,427 strokes, and 116,977 deaths were reported in 1,607,232 patients with type 2 diabetes. After adjusting for conventional risk factors, patients with CKD and NAFLD showed the highest risk of MI and stroke (hazard ratio (HR) 1.49 95% confidence interval (CI) 1.42-1.57 and stroke, HR 1.48 95% CI 1.41-1.54, respectively) compared with those without either CKD or NAFLD. Both overall and cardiovascular mortality were highest in the CKDNAFLD group compared with other groups (HR 2.00 95% CI 1.94-2.06, and HR 2.20 95% CI 2.07-2.35, respectively). Advanced liver fibrosis was significantly associated with an increased risk of CVD in patients with NAFLD. Proteinuria was significantly associated with incidence of CVD events in patients with CKD. The combination of CKD and NAFLD was associated with an increased risk of CVD and mortality in patients with type 2 diabetes. Close monitoring and appropriate management of CKD and NAFLD may be warranted to prevent CVD in these patients.

Early Prediction for Prediabetes and Type 2 Diabetes Using the Genetic Risk Score and Oxidative Stress Score.

We aimed to use a genetic risk score (GRS) constructed with prediabetes and type 2 diabetes-related single nucleotide polymorphisms (SNPs) and an oxidative stress score (OSS) to construct an early-prediction model for prediabetes and type 2 diabetes (T2DM) incidence in a Korean population. The study population included 549 prediabetes and T2DM patients and 1036 normal subjects. The GRS was constructed using six prediabetes and T2DM-related SNPs, and the OSS was composed of three recognized oxidative stress biomarkers. Among the nine SNPs, six showed significant associations with the incidence of prediabetes and T2DM. The GRS was profoundly associated with increased prediabetes and T2DM (OR 1.946) compared with individual SNPs after adjusting for age, sex, and BMI. Each of the three oxidative stress biomarkers was markedly higher in the prediabetes and T2DM group than in the normal group, and the OSS was significantly associated with increased prediabetes and T2DM (OR 2.270). When BMI was introduced to the model with the OSS and GRS, the area under the ROC curve improved (from 69.3% to 70.5%). We found that the prediction model composed of the OSS, GRS, and BMI showed a significant prediction ability for the incidence of prediabetes and T2DM.

Selenium and Selenoproteins at the Intersection of Type 2 Diabetes and Thyroid Pathophysiology.

Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism, Se may be involved in these fundamental relationships it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individuals diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D.

Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion.

Recent studies suggest that PGC1-α plays a crucial role in mitochondrial and vascular function, yet the physiological significance of PGC1α and HO expression in adipose tissues in the context of obesity-linked vascular dysfunction remains unclear. We studied three groups of six-week-old C57BL6J male mice (1) mice fed a normal chow diet (2) mice fed a high-fat diet (H.F.D.) for 28 weeks, and (3) mice fed a high-fat diet (H.F.D.) for 28 weeks, treated with adipose-specific overexpression of PGC-1α (transgenic-adipocyte-PGC-1α) at week 20, and continued on H.F.D. for weeks 20-28. R.N.A. arrays examined 88 genes involved in adipocyte proliferation and maturation. Blood pressure, tissue fibrosis, fasting glucose, and oxygen consumption were measured, as well as liver steatosis, and the expression levels of metabolic and mitochondrial markers. Obese mice exhibited a marked reduction of PGC1α and developed adipocyte hypertrophy, fibrosis, hepatic steatosis, and decreased mitochondrial respiration. Mice with adipose-specific overexpression of PGC1-α exhibited improvement in HO-1, mitochondrial biogenesis and respiration, with a decrease in fasting glucose, reduced blood pressure and fibrosis, and increased oxygen consumption. PGC-1α led to the upregulated expression of processes associated with the browning of fat tissue, including UCP1, FGF21, and pAMPK signaling, with a reduction in inflammatory adipokines, NOVCCN3 expression, and TGFβ. These changes required HO-1 expression. The R.N.A. array analysis identified subgroups of genes positively correlated with contributions to the browning of adipose tissue, all dependent on HO-1. Our observations reveal a positive impact of adipose-PGC1-α on distal organ systems, with beneficial effects on HO-1 levels, reversing obesity-linked cardiometabolic disturbances.

NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes Current Knowledge and Therapeutic Outlook.

Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in hepatocytes, is closely linked to insulin resistance and is the most frequent complication of type 2 diabetes mellitus (T2DM). One of the features connecting NAFLD, insulin resistance and T2DM is cellular oxidative stress. Oxidative stress refers to a redox imbalance due to an inequity between the capacity of production and the elimination of reactive oxygen species (ROS). One of the major cellular ROS sources is NADPH oxidase enzymes (NOX-es). In physiological conditions, NOX-es produce ROS purposefully in a timely and spatially regulated manner and are crucial regulators of various cellular events linked to metabolism, receptor signal transmission, proliferation and apoptosis. In contrast, dysregulated NOX-derived ROS production is related to the onset of diverse pathologies. This review provides a synopsis of current knowledge concerning NOX enzymes as connective elements between NAFLD, insulin resistance and T2DM and weighs their potential relevance as pharmacological targets to alleviate fatty liver disease.

Ameliorative and Antioxidative Potential of

The ameliorative and antioxidative stress effects of probiotic-enriched fermented oat (FOE) or fermented oat with honey (HFOE) extracts on streptozotocin-induced diabetes in rats were examined. The total phenolic content (TPC) and antioxidant activity (AOA) were increased in FOE and HFOE after 72 h of fermentation, and γ-aminobutyric acid (GABA) reached 7.35 mg 100 g

Antioxidant Effect of Tyr-Ala Extracted from Zein on INS-1 Cells and Type 2 Diabetes High-Fat-Diet-Induced Mice.

Type 2 diabetes mellitus (T2DM) is associated with an oxidative milieu that often leads to adverse health problems. Bioactive peptides of zein possess outstanding antioxidant activity however, their effects on hyperglycemia-related oxidative stress remain elusive. In the present study, the dipeptide Tyr-Ala (YA), a functional peptide with typical health benefits, was applied to alleviate oxidative stress in pancreatic islets under hyperglycemic conditions. By detecting viability, antioxidant ability, and insulin secretion in INS-1 cells, YA showed excellent protection of INS-1 cells from H

Critical limb ischemia (CLI) is a severe complication of diabetes mellitus that occurs without effective therapy. Excessive reactive oxygen species (ROS) production and oxidative stress play critical roles in the development of diabetic cardiovascular complications.

Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs.

Nonalcoholic steatohepatitis (NASH) is the most severe manifestation of nonalcoholic fatty liver disease (NAFLD), a common complication of type 2 diabetes, and may lead to cirrhosis and hepatocellular carcinoma. Oxidative stress and liver cell damage are the major triggers of the severe hepatic inflammation that characterizes NASH, which is highly correlated with atherosclerosis and coronary artery disease. Regarding drug therapy, research on the role of GLP-1 analogues and DPP4 inhibitors, novel classes of antidiabetic drugs, is growing. In this review, we outline the association between NASH and atherosclerosis, the underlying molecular mechanisms, and the effects of incretin-based drugs, especially GLP-1 RAs, for the therapeutic management of these conditions.

Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress.

Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDef

Time in range assessed by capillary blood glucose in relation to insulin sensitivity and β-cell function in patients with type 2 diabetes mellitus A cross-sectional study in China.

This study investigated the association of capillary blood glucose (CBG)-assessed time in range (TIR) (3.9-10.0 mmolL) with insulin sensitivity and islet β-cell function. We recruited 455 patients with type 2 diabetes mellitus. Seven-point glucose-profile data (pre- and 120 min post-main meals, bedtime) were collected over three consecutive days. Plasma glucose and serum insulin concentrations were measured at 0, 60, and 120 min after a 100 g standard steamed bread meal test. The homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index were computed to evaluate insulin resistance. The HOMA of β-cell function (HOMA-β) and the area under the curve between insulin and blood glucose (IAUC TIR was positively correlated with the 60 and 120 min insulin values, IAUC Insulin resistance and islet β-cell function are related to capillary blood glucose-assessed TIR.

Functional changes of the gastric bypass microbiota reactivate thermogenic adipose tissue and systemic glucose control via intestinal FXR-TGR5 crosstalk in diet-induced obesity.

Bariatric surgery remains the most effective therapy for adiposity reduction and remission of type 2 diabetes. Although different bariatric procedures associate with pronounced shifts in the gut microbiota, their functional role in the regulation of energetic and metabolic benefits achieved with the surgery are not clear. To evaluate the causal as well as the inherent therapeutic character of the surgery-altered gut microbiome in improved energy and metabolic control in diet-induced obesity, an antibiotic cocktail was used to eliminate the gut microbiota in diet-induced obese rats after gastric bypass surgery, and gastric bypass-shaped gut microbiota was transplanted into obese littermates. Thorough metabolic profiling was combined with omics technologies on samples collected from cecum and plasma to identify adaptions in gut microbiota-host signaling, which control improved energy balance and metabolic profile after surgery. In this study, we first demonstrate that depletion of the gut microbiota largely reversed the beneficial effects of gastric bypass surgery on negative energy balance and improved glucolipid metabolism. Further, we show that the gastric bypass-shaped gut microbiota reduces adiposity in diet-induced obese recipients by re-activating energy expenditure from metabolic active brown adipose tissue. These beneficial effects were linked to improved glucose homeostasis, lipid control, and improved fatty liver disease. Mechanistically, these effects were triggered by modulation of taurine metabolism by the gastric bypass gut microbiota, fostering an increased abundance of intestinal and circulating taurine-conjugated bile acid species. In turn, these bile acids activated gut-restricted FXR and systemic TGR5 signaling to stimulate adaptive thermogenesis. Our results establish the role of the gut microbiome in the weight loss and metabolic success of gastric bypass surgery. We here identify a signaling cascade that entails altered bile acid receptor signaling resulting from a collective, hitherto undescribed change in the metabolic activity of a cluster of bacteria, thereby readjusting energy imbalance and metabolic disease in the obese host. These findings strengthen the rationale for microbiota-targeted strategies to improve and refine current therapies of obesity and metabolic syndrome. Video Abstract Bariatric Surgery (i.e. RYGB) or the repeated fecal microbiota transfer (FMT) from RYGB donors into DIO (diet-induced obesity) animals induces shifts in the intestinal microbiome, an effect that can be impaired by oral application of antibiotics (ABx). Our current study shows that RYGB-dependent alterations in the intestinal microbiome result in an increase in the luminal and systemic pool of Taurine-conjugated Bile acids (TCBAs) by various cellular mechanisms acting in the intestine and the liver. TCBAs induce signaling via two different receptors, farnesoid X receptor (FXR, specifically in the intestines) and the G-protein-coupled bile acid receptor TGR5 (systemically), finally resulting in metabolic improvement and advanced weight management. BSH, bile salt hydrolase BAT brown adipose tissue.

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery.

Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB SG) (41.7 ± 4.6 vs 28.2 ± 6.8% p 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR 0.75 95%CI 0.51-0.91 p 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

Medical complications of obesity heightened importance in a COVID era.

Obesity is a major public health problem associated with significant medical complications. This review examines 8 primary diseases type 2 diabetes, hypertension, dementia, non-alcoholic fatty liver disease, polycystic ovarian syndrome, dyslipidemia, cancer, and their manifestations in obese patients. A total of 39 articles were used for this review. The authors conducted limited review, searching PubMed and Google Scholar databases using a combination of key words COVID-19 or SARS-COV2, type 2 diabetes, hypertension, dementia, non-alcoholic fatty liver disease, polycystic ovarian syndrome, dyslipidemia, cancer, and obesity. No specific date limitation was used. Obesity exacerbates many medical conditions and has recently been identified as an independent risk factor for COVID-19 severity. This sets obesity at the pinnacle of all disease complications. The long-term impact of obesity ranges from financial burden on the health system, lower life expectancy, and reduced survival rates. Obesity is an important modifiable risk factor. There is the need for healthcare providers to understand the medical complications associated with obesity to optimize patient care.

Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.

A single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78182 (42.9%) patients were homozygous wild-type (ThrThr), 83182 (45.6%) heterozygous (ThrAla), and 21182 (11.5%) rare homozygous (AlaAla). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.

Circulating level of homocysteine contributes to diabetic retinopathy associated with dysregulated lipid profile and impaired kidney function in patients with type 2 diabetes mellitus.

To test the hypothesis that elevated plasma levels of homocysteine (Hcy) and lipoprotein (a) (LPA) contribute to diabetic retinopathy (DR) associated with dysregulated lipid profile, dyslipidaemia, and kidney function. A total of 83 patients with type 2 diabetes mellitus (T2DM) were enrolled in this prospective case-control study. Patients were categorized into those with no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR). Age and sex-matched individuals with no diabetes were included in the control group. Biochemical tests, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Hcy, LPA, lipid profile, and urine microalbumin (UMA), were evaluated. Hcy was negatively correlated with high-density lipoprotein-cholesterol (HDL-C) (p < 0.05), but positively correlated with total cholesterol (TC)-HDL-C)HDL-C (p < 0.05), low-density lipoprotein cholesterol (LDL-C)HDL-C (p < 0.05), and UMA (p < 0.05). Traditional risk factors, Hcy, arteriosclerosis-associated plasma indices, and UMA, resulted as the independent risk factors for the occurrence of DM and DR. After controlling for age, sex, duration of DM, and FBG, a multiple ordinal logistic regression model showed that LPA OR 2.90, 95% confidence interval (95% CI) 1.16-7.23, p 0.023), LDL-C (OR 4.28, 95% CI 1.24-14.79, p 0.021), and (TC-HDL-C)HDL-C (OR 1.92, 95% CI 1.05-3.53, p 0.035) were risk factors for DM and DR. Hcy and LPA contributed to DM and DR. Hcy was positively correlated with kidney dysfunction and the ratios of lipid profiles, and negatively with HDL-C, LPA, LDL-C, and (TC-HDL-C)HDL-C resulted as predictors of the occurrence of DM and severity of DR.

Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3KAKT signalling in high fatstreptozotocin-induced diabetic rats.

Rising prevalence of type 2 diabetes mellitus (T2DM) in sub-Saharan Africa has necessitated surveys of antidiabetic medicinal plants. This study assessed the antidiabetic mechanism of Terminalia catappa aqueous leaf extract (TCA) in high fatlow dose streptozotocin-induced type 2 diabetic rats. T2DM was induced by a combination of high-fat diet and low dose STZ (30 mgkg bw) and the animals were administered with TCA (400 and 800 mgkg bw) orally daily for 28 days. Biochemical parameters and indices for diabetes including renal function tests and pancreatic histology were evaluated. Relative expression of hepatic insulin resistance, signalling and glucose transport genes were also assessed. Induction of T2DM resulted in significant (p < 0.05) weight loss, dysregulated glucose level and clearance, electrolyte imbalance and disrupted diabetic biochemical parameters. Diabetes onset also perturbed β-cell function and insulin resistance indices, damaged pancreas microanatomy, while disrupting the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and glucose transporter isoform 4 (GLUT-4) mRNA. Oral treatment of diabetic animals with TCA significantly (p < 0.05) ameliorated alterations due to T2DM induction in a manner comparable with glibenclamide. These results suggest TCA exerts its antidiabetic action by reversing insulin resistance, improving glucose transport and activating PI3KAKT signalling.

Effects of exercise initiation and smoking cessation after new-onset type 2 diabetes mellitus on risk of mortality and cardiovascular outcomes.

Lifestyle changes after a diagnosis of type 2 diabetes mellitus (DM) can affect vascular health outcomes. The objective of this study was to investigate the effects of changes in smoking and exercise on the risk of cardiovascular disease (CVD) and mortality in patients with newly diagnosed DM. Data were analyzed for 181,591 people with newly diagnosed type 2 DM who underwent 2 serial health examinations within 2 years before and after DM diagnosis. The study population was followed from the baseline to the date of death or cardiovascular events, or until December 31, 2018 and median follow-up was 6.07 years. Based on the change in status from before to after the diagnosis, participants were grouped into smoking groups (continuous smokers, quitters, new smokers, and nonsmokers) and exercise groups (constant exercisers, new exercisers, exercise dropouts, and nonexercisers). Compared with the nonexercisers, those who initiated exercise after their DM diagnosis had a lower risk of myocardial infarction (MI), stroke, and all-cause mortality the hazard ratio (HR 95% confidence interval CI) was 0.85 (0.76-0.94) for MI, 0.86 (0.78-0.94) for stroke, and 0.84 (0.89-0.90) for all-cause mortality. Quitters had a higher risk of MI, stroke, and all-cause mortality than nonsmokers, but their risk level was much lower than that in continuous smokers. When the group of continuous smokers and nonexercisers was considered as the reference group, participants who quit smoking and remained nonexercisers had a 21% lower risk of CVD (HR 0.79 95% CI 0.70-0.90). Those who quit smoking and started exercising had a 46% reduced risk of CVD (HR 0.54 95% CI 0.41-0.71) and a 22% reduced risk in all-cause mortality (HR 0.78 95% CI 0.63-0.96). Smoking cessation and exercise initiation after a diagnosis of new-onset type 2 DM was associated with a reduced risk of CVD and all-cause mortality.

Optimization of Care for Adult Outpatients With Type 2 Diabetes Through the Diabetes Self-Management Multidisciplinary Program A Randomized Clinical Trial.

Our aim in this study was to evaluate the efficacy of a Self-Management Multidisciplinary Program (MP) on glycemic management, quality of life and diabetes self-care activities. People with type 2 diabetes and glycated hemoglobin (A1C) of >7.5% were randomized to participate in the MP or to usual care (UC). The MP consisted of face-to-face meetings with each health-care provider (nurse, pharmacist, dietitian, physical educator and social worker) to approach diabetes self-management issues. MP topics were tailored toward local habits and culture. Three different modules were offered over 12 weeks. The primary outcome was change in A1C from baseline to 12 months. Diabetes Quality of Life and Summary of Diabetes Self-Care Activities questionnaires were assessed at baseline and at 6 and 12 months. Ninety-six participants were included (mean 59 years of age, 60% women, diabetes duration 16±10 years, 62% of lower middlelow socioeconomic status). Change in A1C at 12 months (UC 0.52% 95% confidence interval, -1.07 to 0.04 MP -0.30% 95% confidence interval, -1.05 to 0.44 p0.33) was not different between the groups. There was an increase in satisfaction and a reduction in worry about future effects of diabetes in the MP group, which was not found in the UC group. A short-term self-management multidisciplinary program improved diabetes-related quality of life but failed to reduce A1C in individuals with longstanding type 2 diabetes and a low socioeconomic status.

Breastfeeding Rates and Related Factors at 1 Year Postpartum in Women With Gestational Diabetes Initially Recruited for a Diabetes Prevention Program.

Our aim in this study was to evaluate breastfeeding up to 1 year postpartum and factors related to weaning in women with recent gestational diabetes mellitus (GDM). We assembled a cohort study of women with GDM enrolled in prenatal clinics of the Brazilian National Health System as possible candidates for the Lifestyle Intervention for Diabetes Prevention After Pregnancy (LINDA-Brasil) postpartum trial (N2,220). Sociodemographics and clinical and nutritional information, including breastfeeding, were obtained by interview or chart review. Follow-up by telephone was done at specific intervals during the first year postpartum. The probability of breastfeeding at 1 year postpartum, estimated from Kaplan-Meier survival analysis, was 53.5%. Cox regression models showed increased risk of weaning for those introducing milk or formula before 6 months (hazard ratio HR, 2.55 95% confidence interval CI, 2.10 to 3.09) reporting problems in breastfeeding (HR, 1.49 95% CI, 1.22 to 1.82) being Caucasian (HR, 1.46 95% CI, 1.21 to 1.76) smoking during pregnancy (HR, 1.68 95% CI, 1.28 to 2.20) and living in 2 southern cities of Brazil (HR, 1.58 95% CI, 1.16 to 2.16 and HR, 1.76 95% CI, 1.20 to 2.58). About half of the women with GDM ceased breastfeeding before 1 year postpartum, a rate matching that of the general population in Brazil. The main risk factor was not exclusively breastfeeding up to 6 months. Given the possibility of curbing diabetes risk by maintaining longer breastfeeding, further promotion of exclusive breastfeeding up to 6 months for these high-risk women is much needed.

AWAREness of Diagnosis and Treatment of Chronic Kidney Disease in Adults With Type 2 Diabetes (AWARE-CKD in T2D).

Diabetes remains the leading contributor to the development of chronic kidney disease (CKD) and end-stage kidney disease, emphasizing the urgency of identifying barriers to early diagnosis and intervention. The primary objective of this study was to describe the awareness, values and preferences of physicians and patients with respect to managing CKD among patients with type 2 diabetes (T2D). A cross-sectional survey was conducted among physicians and adult patients with T2D and CKD based on estimated glomerular filtration rate and urine albumin-to-creatinine ratio (uACR) measured within 1 year. Physicians were recruited from email networks across Canada, excluding Alberta, and patients were recruited from LMC Diabetes and Endocrinology clinics in Ontario and Quebec. Two separate surveys were developed by a steering committee. Survey responses from 160 physicians (60 general practitioners, 50 endocrinologists and 50 nephrologists) and 169 patients were analyzed descriptively. Gaps in physician care included insufficient use of uACR screening, limited knowledge or use of Kidney Disease Improving Global Outcomes (KDIGO) and KidneyWise resources and lower than expected prescription of recommended therapies. The patient data showed 51.5% of patients were unaware of a CKD diagnosis, and 75.6% of patients who received a prior CKD diagnosis would have preferred an earlier diagnosis. The results highlight several opportunities for improving CKD in T2D management. More education and clarity are needed for physicians interpreting uACR levels that should prompt a referral to a nephrologist, and additional understanding of kidney risk progression is vital for patients.

Tis Better to Give Than to Receive Health-related Benefits of Delivering Peer Support in Type 2 Diabetes An Explanatory Sequential Mixed-methods Study.

Existing peer support literature in diabetes has focussed predominantly on the health impact it has on the beneficiaries rather than the benefactors. In this mixed-methods study, we examined the effect of delivering peer support (vs receiving) on glycated hemoglobin (A1C) and diabetes distress (DD) at 3 and 12 months as part of a larger diabetes self-management support randomized controlled trial. Maintenance or improvement of outcomes was expected. We also assessed peer leaders experiences with the program. We utilized a sequential explanatory mixed-methods research design that included 58 adults with diabetes (i.e. peer leaders) who completed a 30-hour training program. Peer leaders (n52) were matched with participants (adults with type 2 diabetes) and invited to undergo assessments at baseline, 3 months and 12 months. Primary clinical and psychosocial outcomes included A1C and DD, respectively. Secondary outcomes were cardiovascular risk factors and depressive symptoms. After the intervention, 17 peer leaders participated in semistructured interviews about their experience. Peer leaders had a mean age of 57.5±11 years and a long history of diabetes (13.9±11 years) over half were male (53.8%) and marriedpartnered (55.8%). At baseline, peer leaders were at target for A1C (7.0±0.9% 53±10 mmolmol) and reported a low level of DD (1.67±0.52). Of the 43 (82.7%) peer leaders who completed the 12-month study, A1C and DD remained stable over 12 months. Secondary outcomes also remained within the normal range from the start to the end of the intervention. Delivering peer support may help maintain glycemic control and DD over the long term.

Low Use of Guideline-recommended Cardiorenal Protective Antihyperglycemic Agents in Primary Care A Cross-sectional Study of Adults With Type 2 Diabetes.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardiorenal benefits independent of their glucose-lowering effects among persons living with type 2 diabetes mellitus (T2DM). In this study, we describe the proportion of persons with T2DM eligible to receive and currently receiving these agents based on their risk criteria for cardiorenal events. This study was a cross-sectional analysis of primary care electronic medical records, in southern Alberta, of persons with T2DM who had at least 1 encounter with their primary care provider between December 31, 2018, to December 31, 2020. A descriptive and multivariate logistic regression analysis was conducted to examine clinical and demographic determinants of being prescribed one of the new treatments. Our study sample included 11,939 persons living with T2DM, among whom 66.3% had a cardiorenal indication for SGLT2i or GLP-1 RA use. In the secondary and primary prevention subsamples, 19.4% and 16.6% of persons were prescribed SGLT2i or GLP-1 RA, respectively, compared with 20.0% of those with no specific cardiorenal indication. Several person-level characteristics, such as age (odds ratio OR, 0.96 95% confidence interval CI, 0.96 to 0.97), male sex (OR, 1.37 95% CI, 1.21 to 1.55) and glycated hemoglobin (OR, 1.29 95% CI, 1.24 to 1.34), were associated with being prescribed SGLT2i or GLP-1 RA. Low rates of SGLT2i or GLP-1 RA use and minimal differences between high-risk and no cardiorenal indication subsamples suggest the presence of barriers to prescribing these medications in a primary care setting. Action to highlight the indications for, and improve access to agents with, cardiorenal benefits will be required to achieve better outcomes for people with T2DM in primary care.

Benefits and Harms of Deprescribing Antihyperglycemics for Adults With Type 2 Diabetes A Systematic Review.

Contemporary guidelines suggest relaxed glycemic targets in populations with type 2 diabetes mellitus (T2DM) at risk of hypoglycemia, including people with multimorbidity, limited life expectancy or frailty. However, overtreatment remains commonplace. To inform safe deprescribing, a previous systematic review investigated the benefits and harms of deprescribing antihyperglycemics, but identified only limited, very low-quality evidence. We sought to update that review and identify and describe newly published literature on the effects of deprescribing antihyperglycemics in older adults with T2DM. We searched MEDLINE, EMBASE and the Cochrane Library (July 2015 to January 2021) for controlled studies published in English addressing the effects of deprescribing vs continuing antihyperglycemics in adults with T2DM. Two independent reviewers performed title, abstract and full-text screening, data extraction and risk-of-bias assessment. Cochranes risk-of-bias tools, RoB 2 and ROBINS-I, were used. The findings were summarized narratively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to evaluate the evidence. We identified 4 additional investigations-2 randomized controlled trials and 2 retrospective cohort studies. After deprescribing, 3 studies reported no clinically significant changes in glucose management and 2 studies reported reductions in adverse events (e.g. hypoglycemia, all-cause mortality and nonspine fractures). However, based on GRADE assessment, we found very low certainty of the evidence due to concerns of risk of bias (e.g. unmeasured confounding), imprecision, and indirectness. Deprescribing antihyperglycemic medications in older adults with T2DM is likely feasible and safe, and benefits may outweigh the harms. However, the evidence indicates very low certainty. Additional deprescribing studies are needed with rigorous methodologies and reporting.

The effect of food access on type 2 diabetes control in patients of a New Orleans, Louisiana, clinic.

The U.S. Department of Agriculture (USDA) classifies numerous neighborhoods in New Orleans, Louisiana, as food deserts or areas with inadequate access to good quality foods. With approximately 35% of all patients with type 2 diabetes (T2DM) establishing disease control, we hypothesize those living in food deserts will have increased difficulty in controlling T2DM. The purpose of this study is to evaluate the effect of food deserts on glycemic control in patients with T2DM. The purpose of this study is to analyze the effect of food access on T2DM control in patients at a diabetes management clinic compared with the national average of T2DM control. Eligible records for review included patients residing in a USDA-determined food desert with a T2DM diagnosis. The primary end point was the proportion of patients with controlled T2DM. T2DM control was defined as glycosylated hemoglobin values less than 7% and less than 7.5% in patients older than 65 years. Records were retrieved for review between the dates of February 2017 and February 2020. A total of 109 patient records were reviewed. Of these, 23 patients (21%) achieved glycemic control. There was a 14% difference (35%-21%) between the food desert patients with T2DM and the general United States population of patients with T2DM (P 0.030). This study underscores the potential implications of limited food access on patients abilities to manage chronic conditions like T2DM. Clinicians who work in resource-limited settings or with marginalized patient populations have a responsibility to consider food access and other health disparities when creating realistic and feasible treatment goals.

Relationship between serum creatinine to cystatin C ratio and subclinical atherosclerosis in patients with type 2 diabetes.

Sarcopenia index (SI), calculated by (serum creatininecystatin C)×100, is reported to be associated with sarcopenia. Few studies reported the association between SI and subclinical atherosclerosis. We evaluated the association between SI and subclinical atherosclerosis, assessed by brachial-ankle pulse wave velocity (baPWV). One hundred seventy-four patients with type 2 diabetes were included in this cross-sectional study. The relationship between SI and baPWV was assessed by Pearsons correlation coefficient. To calculate area under the receiver operator characteristic (ROC) curve (AUC) of SI for the presence of subclinical atherosclerosis, which was defined as baPWV >1800 cms, ROC analysis was performed. Logistic regression analyses were performed to assess the effect of SI on the prevalence of subclinical atherosclerosis adjusting for covariates. Mean age, duration of diabetes, baPWV, and SI were 66.9 (10.1) years, 17.7 (11.6) years, 1802 (372) cms, and 77.6 (15.8), respectively. There was an association between SI and baPWV (men r-0.25, p0.001, and women r-0.37, p0.015). The optimal cut-off point of SI for the presence of subclinical atherosclerosis was 77.4 (sensitivity0.72, specificity0.58, p<0.001, AUC 0.66 (95% CI 0.57 to 0.74)). In addition, SI was associated with the prevalence of subclinical atherosclerosis (adjusted OR 0.95, 95% CI 0.91 to 0.99, p0.015). SI is associated with the prevalence of subclinical atherosclerosis in patients with type 2 diabetes.

Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure.

Beta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), known as quadruple therapy, are recommended for patients with heart failure with reduced ejection fraction (HFrEF). This study sought to determine Medicare coverage and out-of-pocket (OOP) costs of quadruple therapy and regimens excluding ARNI or SGLT2i. This study assessed cost sharing, prior authorization, and step therapy in all 4,068 Medicare prescription drug plans in 2020. OOP costs were determined during the standard coverage period and annually based on the Medicare Part D standard benefit, inclusive of deductible, standard coverage, coverage gap, and catastrophic coverage. Tier ≥3 cost sharing was required by 99.1% of plans for ARNI and 98.5% for at least 1 SGLT2i. Only ARNI required prior authorization (24.3% of plans), and step therapy was required only for SGLT2is (5.4%) and eplerenone (0.8%). The median 30-day standard coverage OOP cost of quadruple therapy was $94 (IQR $84-$100), including $47 (IQR $40-$47) for ARNI and $45 (IQR $40-$47) for SGLT2i. The median annual OOP cost of quadruple therapy was $2,217 (IQR $1,956-$2,579) compared with $1,319 (IQR $1,067-$1,675) when excluding SGLT2i and $1,322 (IQR $1,025-$1,588) when including SGLT2i and substituting an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ARNI. The median 30-day OOP cost of generic regimens was $3 (IQR $0-$9). Medicare drug plans restrict coverage of quadruple therapy through cost sharing, with OOP costs that are substantially higher than generic regimens. Quadruple therapy may be unaffordable for many Medicare patients with HFrEF unless medication prices and cost sharing are reduced.

Evidence for Indoxyl Sulfate as an Inducer of Oxidative Stress in Patients With Diabetes.

Indoxyl sulfate is a metabolite of tryptophan and its urinary level reflects the status of bacterial flora in the intestine. Indoxyl sulfate possesses prooxidant properties and is implicated in various diseases including chronic kidney disease and cardiovascular diseases. However, the relation of urinary indoxyl sulfate to oxidative stress is not known. The association of urinary indoxyl sulfate levels with urinary levels of oxidative stress markers, 15-isoprostane F Urinary levels of indoxyl sulfate, pteridines, and 15-isoprostane F Urinary indoxyl sulfate levels showed associations with urinary levels of oxidative stress markers, and the associations were independent of age, sex, insulin therapy for diabetes, body mass index, blood pressure, glycemic status, renal function, smoking, and alcohol drinking. Indoxyl sulfate appears to be an important determinant of redox balance in patients with diabetes.

The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists.

In the last few years, a great interest has emerged in investigating the pleiotropic effects of Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs). While GLP-1RAs ability to lower plasma glucose and to induce weight loss has allowed them to be approved for the treatment of diabetes and obesity, consistent evidences from in vitro studies and preclinical models suggested that GLP-1RAs have anti-inflammatory properties and that may modulate the immune-system. Notably, such anti-inflammatory effects target different pathways in different tissues, underling the broad spectrum of GLP-1RAs actions. This review examines some of the currently proposed molecular mechanisms of GLP-1RAs actions and explores their potential benefits in reducing inflammatory responses, which may well suggest a future therapeutic use of GLP-1RAs in new indications.

Effectiveness and Ethical Evaluation of Nudging to Promote the Self-Management in Diabetes Mellitus Type 2.

Nudges offer a wide range of options for protecting health in everyday life that supplements traditional public health measures. Against this background, we conducted initial investigations on the effectiveness and ethical aspects of different nudges for promoting self-management of patients with diabetes mellitus type 2 in the context of Disease Management Programs (DMPs). The ethical assessment of the nudges was done within the systematic framework of Marckmann et al. (2015) for public health ethics. The existing evidence on the effectiveness of nudges was summarised by means of a narrative literature review. Target agreements with implementation plans, reminder, feedback reports, shared appointments of patients with physicians, peer mentoring, and behavior contracts are nudging interventions with moderate interference with personal rights and relatively unproblematic ethical requirements, which have demonstrated effectiveness in different contexts. Default enrollment for patient training courses, involvement of partners, confrontation with social norms, and shocking pictures may be effective as well however, they interfere more deeply with the freedom and privacy of patients and, therefore, are bound to stronger ethical requirements and restrictions. The evidence base is still insufficient, especially for social support measures by relatives and peers. Nudging offers a wide range of targeted interventions for supporting self-management of patients with chronic diseases, the potential of which has not yet been fully realized. Particularly promising interventions should be tested in pilot studies for their acceptance, effectiveness and cost-effectiveness in the context of DMPs. Nudges bieten vielfältige Möglichkeiten zur Förderung von gesundheitsbezogenem Verhalten im Alltag, die klassische Public Health-Maßnahmen ergänzen können. Vor diesem Hintergrund führten wir vorläufige Untersuchungen zur Wirksamkeit und zu ethischen Aspekten verschiedener Nudges zur Förderung des Selbstmanagements von Patienten mit Diabetes mellitus Typ 2 im Kontext von Disease-Management-Programmen (DMPs) durch. Die ethische Bewertung der Nudges erfolgte im systematischen Rahmen von Marckmann et al. (2015) zur Public Health-Ethik. Die bisherige Evidenz zur Wirksamkeit von Nudges wurde mittels einer narrativen Literaturübersicht zusammenfassend dargestellt. Zielvereinbarungen mit Umsetzungsplänen, Erinnerungen, Feedback, Sammeltermine bei Ärzten, Peer Mentoring sowie Verhaltensverträge sind Nudging-Interventionen mit mäßiger Eingriffstiefe in die Persönlichkeitsrechte der Patienten und ethisch relativ unproblematischen Voraussetzungen, die sich in verschiedenen Kontexten bewährt haben. Automatische Einschreibungen zu Patientenschulungen, Einbindung der Lebenspartner, Konfrontation mit sozialen Normen und Verwendung von Schockbildern können ebenfalls wirksam sein, greifen jedoch tiefer in die Freiheit und Privatsphäre der Patienten ein und unterliegen stärkeren ethischen Voraussetzungen und Beschränkungen. Die Evidenzlage ist insbesondere bei Maßnahmen zur sozialen Unterstützung durch Angehörige und Peers noch unzureichend. Nudging bietet ein breites Spektrum gezielter Interventionen zur Förderung des Selbstmanage-ments von Patienten mit chronischen Erkrankungen, dessen Potenzial bislang noch zu wenig erschlossen wurde. Besonders vielversprechende Maßnahmen sollten in Pilotstudien auf ihre Akzeptanz, Wirksamkeit und Kosteneffektivität im Rahmen von DMPs evaluiert werden.

Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment.

Sex hormone binding globulin (SHBG) is a hepatokine that binds to circulating steroid hormones (testosterone, oestradiol) to regulate their concentration in the bloodstream. Recently SHBG was recognized as an essential biomarker for metabolic syndrome (MetS) and hepatic steatosis development. At the hepatic level, the production of SHBG is mainly regulated by sex steroids and thyroxine. Studies of various research groups, including ours, showed that SHBG could be considered a reliable marker of insulin resistance and, therefore, can serve as a predictor of type 2 diabetes. Moreover, increased levels of circulating pro-inflammatory mediators strongly correlate with lowered serum levels of SHBG. This review paper emphasizes the role of SHBG as a potential drug candidate in the course of various metabolic dysfunctions, including non-alcoholic fatty liver disease (NAFLD), obesity, diabetes mellitus and insulin resistance. The studies related to SHBG and its role in the course of metabolic disorders are very limited. Here, we have summarized the most current knowledge about SHBG and its mechanism of action, indicating a novel concept for its possible therapeutic application in the management framework of commonly occurring metabolic dysfunctions.

Atypical parathyroid adenoma Series of two consecutive cases from a tertiary care hospital in Qatar.

Atypical parathyroid adenomas (APA) are an uncommon cause of hypercalcemia and comprise a minority of parathyroid adenomas. Case 1 - Egyptian male, 48 years old with history of type 2 diabetes mellitus, incidentally discovered increased serum of calcium level on routine investigation, was diagnosed as PHPT, US and MIBI scan showed large left inferior parathyroid adenoma, focused exploration and excision of the APA was undertaken, histopathology confirmed APA. Case 2 - Egyptian male, 60 years old, cardiac patient with history of diabetes, hypertension and multiple cardiac interventions, had nausea, vomiting, constipation abdominal pain, polyuria, polydipsia, and history of passing renal stones, hypercalcemia workup showed primary hyperparathyroidism (PHPT), MIBI was negative and SPECT scan suggested right inferior parathyroid adenoma, focused exploration and excision of the APA was undertaken, histopathology confirmed APA. APA are an uncommon cause of hypercalcemia and are responsible for a minority of parathyroid adenomas. Combined US and MIBI and SPECT scans can detect APA. Focused exploration and excision of the APA under general anaesthesia can completely remove the APA. Awareness of the physician and a high index of suspicion to symptoms or signs that could reflect an underlying PHPT is essential. Yearly biochemical and neck US follow up are required to detect any risk of recurrence or malignancy in the long term.

Nonivamide induces brown fat-like characteristics in porcine subcutaneous adipocytes.

Obesity, which is associated with type 2 diabetes, is a threat to human health. There are studies, which suggest that some compounds can induce browning of white adipocytes to combat obesity. In this study, we selected nonivamide, an analog of capsaicin, to detect whether it influenced the browning of porcine white adipocytes. First, we found 25 μM nonivamide promoted apoptosis of porcine subcutaneous pre-adipocytes. After pre-adipocytes differentiation, nonivamide inhibited adipogenesis by reducing the expressions of Pparγ, Cebpα, while it promoted lipolysis by up-regulating Hsl, Atgl. Nonivamide also induced browning of porcine subcutaneous adipocytes by up-regulating the expression of brown and beige adipocyte gene markers, such as Prdm16, Cidea, and Slc27a1. Additionally, thermogenesis gene markers Cpt1a and Cpt1b were significantly up-regulated by nonivamide. Furthermore, nonivamide promoted mitochondrial biogenesis by up-regulating the expression of Tfam, Nrf1, Nrf2, and Tomm20. In conclusion, nonivamide is a potent compound to induce porcine adipocyte browning for treating obesity.

Network pharmacology integrated molecular dynamics reveals the bioactive compounds and potential targets of Tinospora crispa Linn. as insulin sensitizer.

Insulin resistance is a metabolic disorder characterized by the decreased response to insulin in muscle, liver, and adipose cells. This condition remains a complex phenomenon that involves several genetic defects and environmental stresses. In the present study, we investigated the mechanism of known phytochemical constituents of Tinospora crispa and its interaction with insulin-resistant target proteins by using network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Tinoscorside A, Makisterone C, Borapetoside A and B, and β sitosterol consider the main phytoconstituents of Tinospora crispa by its binding with active sites of main protein targets of insulin resistance potential therapy. Moreover, Tinoscorside A was revealed from the docking analysis as the ligand that binds most strongly to the target protein, PI3K. This finding was strengthened by the results of MD simulation, which stated that the conformational stability of the ligand-protein complex was achieved at 15 ns and the formation of hydrogen bonds at the active site. In conclusion, Tinospora crispa is one of the promising therapeutic agent in type 2 diabetes mellitus management. Regulation in glucose homeostasis, adipolysis, cell proliferation, and antiapoptosis are predicted to be the critical mechanism of Tinospora crispa as an insulin sensitizer.

The association between aging-related monocyte transcriptional networks and comorbidity burden the Multi-Ethnic Study of Atherosclerosis (MESA).

Translating our knowledge of the biological aging from animal models to humans may give rise to novel approaches of targeting multiple aging-related diseases simultaneously and increasing health span. Here, for the first time, we use transcriptomic signatures of monocytes to identify biological aging pathways underlying multiple aging-related diseases in humans. The ordinal logistic regression was used to cross-sectionally investigate transcriptomics of the comorbidity index in 1264 community-based Multi-Ethnic Study of Atherosclerosis (MESA) adults, 47% Caucasian, 32% Hispanic, 21% African American, and 51% female, aged 55-94 years. The comorbidity index was defined as the number of prevalent aging-related diseases including cardiovascular disease, type-2 diabetes, hypertension, cancer, dementia, chronic kidney disease, chronic obstructive pulmonary disease, and hip fracture. We identified 708 gene transcripts associated with the comorbidity index (FDR < 0.05) after adjusting for age, sex, ethnicity, and study site. In a weighted gene co-expression network analysis, as postulated, aging-related declines in apoptosisautophagy (OR 1.21 per SD increment, p 0.0006) and ribosomemitochondrion (OR 0.90 per SD increment, p 0.05) were positively associated with the comorbidity index. After adjusting for multiple comparisons, we identified 10 comorbidity-associated modules (FDR < 0.05), including the module of apoptosisautophagy. There were three inter-correlated modules of these 10 involved in the complement subcomponent C1q, Fc gamma receptor I, and Fc gamma receptor III of the immune system, respectively. Aging-related upregulation of these three modules was positively associated with the comorbidity index. The odds of comorbidity increased with more of these modules acting together in a dose-response fashion. In conclusion, transcriptomic analysis of human immune cells may identify biomarker panels indicative of comprehensive biological mechanisms, especially immune signaling pathways, contributing to health aging.

Search for a time- and cost-saving genetic testing strategy for maturity-onset diabetes of the young.

Correct genetic diagnosis of maturity-onset diabetes of the young (MODY) is beneficial for persons diabetes management compared to no genetic testing. Aim of the present study was a search for optimal time- and cost-saving strategies by comparing two approaches of genetic testing of participants with clinical suspicion of MODY. A total of 121 consecutive probands referred for suspicion of MODY (Group A) were screened using targeted NGS (tNGS), while the other 112 consecutive probands (Group B) underwent a single gene test based on phenotype, and in cases of negative findings, tNGS was conducted. The study was performed in two subsequent years. The genetic results, time until reporting of the final results and financial expenses were compared between the groups. MODY was confirmed in 30.6% and 40.2% probands from Groups A and B, respectively GCK-MODY was predominant (72.2% in Group A and 77.8% in Group B). The median number of days until results reporting was 184 days (IQR 122-258) in Group A and 91 days (44-174) in Group B (p < 0.00001). Mean costs per person were higher for Group A (639 ± 30 USD) than for Group B (584 ± 296 USD p 0.044). The two-step approach represented a better strategy for genetic investigation of MODY concerning time and costs compared to direct tNGS. Although a single-gene investigation clarified the diabetes aetiology in the majority of cases, tNGS could reveal rare causes of MODY and expose possible limitations of both standard genetic techniques and clinical evaluation.

Serum Ferritin in Metabolic Syndrome-Mechanisms and Clinical Applications.

Metabolic syndrome (MS) is a cluster of conditions including central obesity, hypertriglyceridemia, low HDL cholesterol, hyperglycaemia, and hypertension with a prevalence rate of 20-25% of the worlds adult population. Metabolic syndrome is often characterized by insulin resistance, which some have suggested is a major supportive connection between physical inactivity and MS. Various studies suggest that moderately elevated iron and ferritin levels are associated with an increased prevalence of metabolic syndrome and are markers of insulin resistance. Increased body iron stores are associated with the development of glucose intolerance, type 2 diabetes mellitus, and insulin resistance syndrome (IRS). This is a hospital-based cross-sectional observational study, which was conducted in the department of internal medicine of a tertiary care hospital in northern India. The study was conducted from 1 January 2019 to 30 June 2020 and included 100 patients and 100 controls. All subjects in the age group of 35-65 years were enrolled and investigated as per the study design. Metabolic syndrome patients were diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP-III) with BMI gt 23 kgm

α-Glucosidase inhibitory effect of an anthraquinonoid produced by Fusarium incarnatum GDZZ-G2.

α-Glucosidase is the key enzyme on carbohydrate metabolism, and its bioactive inhibitors are supposed to be an effective therapeutic for type 2 diabetes mellitus. During our continuing study for discovering α-glucosidase inhibitors, a fungus GDZZ-G2 which is derived from a medicinal plant Callicarpa kwangtungensis Chun, exhibited significant inhibition on α-glucosidase. The strain was identified as Fusarium incarnatum by morphological and molecular methods. Further bioassay-guided fractionation result in six known secondary metabolites (1-6). All the compounds except 4 were isolated from F. incarnatum for the first time. Among them, an anthraquinonoid (S)-1,3,6-trihydroxy-7-(1-hydroxyethyl)anthracene-9,10-dione (compound 1) exhibited strong inhibitory effect against α-glucosidase (IC

Investigating Potential GLP-1 Receptor Agonists in Cyclopeptides from

GLP-1 receptor agonists stimulate GLP-1R to promote insulin secretion, whereas DPP4 inhibitors slow GLP-1 degradation. Both approaches are incretin-based therapies for T2D. In addition to GLP-1 analogs, small nonpeptide GLP-1RAs such as LY3502970, TT-OAD2, and PF-06882961 have been considered as possible therapeutic alternatives.

mGWAS-Explorer Linking SNPs, Genes, Metabolites, and Diseases for Functional Insights.

Tens of thousands of single-nucleotide polymorphisms (SNPs) have been identified to be significantly associated with metabolite abundance in over 65 genome-wide association studies with metabolomics (mGWAS) to date. Obtaining mechanistic or functional insights from these associations for translational applications has become a key research area in the mGWAS community. Here, we introduce mGWAS-Explorer, a user-friendly web-based platform to help connect SNPs, metabolites, genes, and their known disease associations via powerful network visual analytics. The application of the mGWAS-Explorer was demonstrated using a COVID-19 and a type 2 diabetes case studies.

Novel Plasma Metabolomic Markers Associated with Diabetes Progression in Older Puerto Ricans.

We assessed longitudinal associations between plasma metabolites, their network-derived clusters, and type 2 diabetes (T2D) progression in Puerto Rican adults, a high-risk Hispanic subgroup with established health disparities. We used data from 1221 participants free of T2D and aged 40-75 years at baseline in the Boston Puerto Rican Health and San Juan Overweight Adult Longitudinal Studies. We used multivariable Poisson regression models to examine associations between baseline concentrations of metabolites and incident T2D and prediabetes. Cohort-specific estimates were combined using inverse-variance weighted fixed-effects meta-analyses. A cluster of 13 metabolites of branched chain amino acids (BCAA), and aromatic amino acid metabolism (pooled IRR 1.87, 95% CI 1.28 2.73), and a cell membrane component metabolite cluster (pooled IRR 1.54, 95% CI 1.04 2.27) were associated with a higher risk of incident T2D. When the metabolites were tested individually, in combined analysis, 5 metabolites involved in BCAA metabolism were associated with incident T2D. These findings highlight potential prognostic biomarkers to identify Puerto Rican adults who may be at high risk for diabetes. Future studies should examine whether diet and lifestyle can modify the associations between these metabolites and progression to T2D.

Identification of Insulin Resistance Biomarkers in Metabolic Syndrome Detected by UHPLC-ESI-QTOF-MS.

Metabolic syndrome (MetS) is a disorder characterized by a group of factors that can increase the risk of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus (T2D). Metabolomics has provided new insight into disease diagnosis and biomarker identification. This cross-sectional investigation used an untargeted metabolomics-based technique to uncover metabolomic alterations and their relationship to pathways in normoglycemic and prediabetic MetS participants to improve disease diagnosis. Plasma samples were collected from drug-naive prediabetic MetS patients (

Fibroblast Growth Factor 23 and Cardiovascular Risk in Diabetes Patients-Cardiologists Be Aware.

Numerous clinical studies have indicated that elevated FGF23 (fibroblast growth factor 23) levels may be associated with cardiovascular (CV) mortality, especially in patients with chronic kidney disease. The purpose of this study was to examine the hypothesis that FGF23 may be a potent CV risk factor among patients with long-standing type 2 diabetes mellitus (T2DM). Research was performed utilizing patients with T2DM and regular outpatient follow-up care. Baseline characteristics determined by laboratory tests were recorded. Serum FGF23 levels were detected using a sandwich enzyme-linked immunosorbent assay. All patients underwent echocardiograms and 12-lead electrocardiograms. Data records of 102 patients (males 57%) with a median age of 69 years (interquartile range (IQR) 66.0-74.0) were analyzed. Baseline characteristics indicated that one-third (33%) of patients suffered from ischemic heart disease (IHD), and the median time elapsed since diagnosis with T2DM was 19 years (IQR 14.0-25.0). The hemoglobin A1c, estimated glomerular filtration rate, and FGF23 values were, respectively, as follows 6.85% (IQR 6.5-7.7), 80 mLmin1.73 m

The Kynurenine Pathway in Obese Middle-Aged Women with Normoglycemia and Type 2 Diabetes.

We examined the relationships of tryptophan (Trp) and the metabolites of the kynurenine pathway (KP) to the occurrence of type 2 diabetes (T2D) and metabolic risk factors in obese middle-aged women. The study included 128 obese women divided into two subgroups a normoglycemic group (NG,

Vitamin B12 Deficiency and Clinical Neuropathy with Metformin Use in Type 2 Diabetes.

Exercise and Nutrition Strategies for Combating Sarcopenia and Type 2 Diabetes Mellitus in Older Adults.

Medical and technology development have drastically the improved quality of life and, consequently, life expectancy. Nevertheless, the more people who enter the third-age, the more geriatric syndromes expand in the elderly. Sarcopenia and Type 2 diabetes mellitus (T2DM) are common diseases among the elderly and the literature has extensively studied these two diseases separately. Recent evidence, however, revealed that there is a bidirectional relationship between sarcopenia and T2DM. The aims of the present review were (1) to present diet and exercise interventions for the management of sarcopenia and T2DM and (2) identify which diet and exercise interventions can be used simultaneously in order to effectively deal with these two disorders. Exercise and a balanced diet are used as effective countermeasures for combating sarcopenia and T2DM in older adults based on their bidirectional relationship. Lifestyle changes such as exercise and a balanced diet seem to play an important role in the remission of the diseases. Results showed that chronic exercise can help towards glycemic regulation as well as decrease the incidence rate of muscle degradation, while diet interventions which focus on protein or amino acids seem to successfully treat both disorders. Despite the fact that there are limited studies that deal with both disorders, it seems that a combined exercise regime (aerobic and resistance) along with protein intake gt 1grkgd is the safest strategy to follow in order to manage sarcopenia and T2DM concurrently.

The renoprotective effect of once-weekly GLP-1 receptor agonist dulaglutide on progression of nephropathy in Japanese patients with type 2 diabetes and moderate to severe chronic kidney disease (JDDM67).

Few studies have investigated the renoprotective effect of glucagon-like peptide-1 (GLP-1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4. Dulaglutide (group A) and non-dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years. In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score-adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kgm Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.

A Study on the Safety and Effects of

Metabolic syndrome is characterized by a variety of diagnostic criteria obesity, dyslipidemia, type 2 diabetes, and arterial hypertension. They contribute to the elevated risk of cardiovascular morbidity and mortality. The potential for

Discovering Engagement Personas in a Digital Diabetes Prevention Program.

Digital health technologies are shaping the future of preventive health care. We present a quantitative approach for discovering and characterizing engagement personas longitudinal engagement patterns in a fully digital diabetes prevention program. We used a two-step approach to discovering engagement personas among

Incidence changes in risk factors associated with the decreasing number of birth-related clavicle fractures in Finland A nationwide retrospective birth cohort from 2004 to 2017.

A clavicle fracture is one of the most common birth injuries. The objective of this study was to examine whether the decreased incidence of birth-related clavicle fractures in Finland is because of temporal changes in their predisposing factors. For this nationwide population-based study, we used the Finnish Medical Birth Register and the Care Register for Health Care databases. The study population included all singleton, live-born newborn born spontaneously or by vacuum-assisted delivery, in cephalic presentation ≥37 A total of 629 457 newborn were born vaginally between 2004 and 2017. The clavicle fracture incidence decreased from 17.61000 to 6.21000 live births. Shoulder dystocia, diabetes, and birthweight ≥4000 g were the strongest predisposing factors. The incidence of birthweight ≥4000 g decreased, meanwhile type 1 diabetes and shoulder dystocia remained stable and gestational diabetes, type 2 diabetes, and maternal obesity increased in the later study period. The incidence of clavicle fractures without known predisposing factors declined. Simultaneously, the cesarean birth rate remained stable (13.2%-13.1%), although the rate of vacuum-assisted deliveries increased (8.5%-9.5%). The incidence of clavicle fractures decreased, even though the incidence of most risk factors remained stable or increased, and the cesarean birth rate remained stable. This decline may be related to the reduction of fracture incidence among deliveries without known risk factors, and the decrease in birthweight ≥4000 g.

A randomized, placebo-controlled clinical trial of hydrogenoxygen inhalation for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide with increasing incidence consistent with obesity, type 2 diabetes and cardiovascular diseases. No approved medication was currently available for NAFLD treatment. Molecular hydrogen (H