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Yunvjian Improves Glucose and Insulin Function in Diabetic Rats by Regulating Gastric Emptying Function.

Diet acts on the human body through digestion in the stomach and absorption in the intestines. Thus, the emptying of the stomach should be the focus of the research mechanism of the combined medicine and food treatment of diabetes. The emptying function of the stomach and the secretion of related hormones may be the key points of traditional Chinese medicine. In the clinic, Yunvjian is a famous traditional Chinese formula for preventing and curing diabetes. However, the pharmacological action and mechanism of Yunvjian are also need to be probe. To assess the effect of Yunvjian on glucose, insulin level and gastric emptying function and related hormones on high-fat diet combined with STZ-induced diabetic rats. High-fat diet combined with STZ was used to construct type 2 diabetes mellitus (T2DM) rats model and received a 4-week Yunvjian administration. The animals were divided into 6 groups, respectively, as the Control group, the DM group, the DM Acarbose group, the DM YNH group, and the DM YNL group. Radionuclide single-photon emission computed tomography (SPECT) technology was used to observe the gastric emptying rate and half-empty time blood was took to test fasting insulin, and then the insulin resistance index (HOMA-IR) was calculated HE staining was performed to detect islets and gastric antrum, immunohistochemical staining was performed to detect the number and morphology of pancreatic Yunvjian could significantly improve the glucose level and insulin function of rats. Compared with the DM group, Yunvjian was beneficial to low fasting blood glucose (FBG) ( Yunvjian can effectively control glucose and improve islet function, which may be closely related to its influence on gastric emptying function and related hormone secretion regulation.

The changing food environment and neighborhood prevalence of type 2 diabetes.

In this ecological study, we used longitudinal data to assess if changes in neighborhood food environments were associated with type 2 diabetes mellitus (T2DM) prevalence, controlling for a host of neighborhood characteristics and spatial error correlation. We found that the population-adjusted prevalence of fast-food and pizza restaurants, grocery stores, and full-service restaurants along with changes in their numbers from 1990 to 2010 were associated with 2015 T2DM prevalence. The results suggested that neighborhoods where fast-food restaurants have increased and neighborhoods where full-service restaurants have decreased over time may be especially important targets for educational campaigns or other public health-related T2DM interventions.

Acute decompensation of patient following an outpatient CT-guided needle biopsy A case report.

A 74-year-old female with history of type 2 diabetes, hypertension, and uterine adenocarcinoma presented for CT-guided lung biopsy that was ultimately complicated by an arterial air embolus requiring intensive care. Systemic air embolism is a very rare event but can be devastating. Prompt recognition can be difficult due to an often-vague presentation but is essential and should be considered upon rapid deterioration of a patients status following high risk procedures. Hyperbaric oxygen therapy is preferred however, if this is unavailable, additional treatments are predominately supportive care with 100% supplemental oxygen, rapid volume expansion, and ionotropic medications as needed.

Efficacy and safety of semaglutide for weight management evidence from the STEP program.

Obesity is a global health challenge. It is a multifactorial, complex, and progressive disease associated with various health complications and increased mortality. Lifestyle modifications are central to weight management but may be insufficient to maintain clinically meaningful weight loss. Pharmacotherapies are recommended as an adjunct to lifestyle interventions to induce and sustain clinically meaningful weight loss and reduce the risk of comorbidities in appropriate patients. Glucagon-like peptide-1 is an incretin metabolic hormone responsible for a range of physiological effects, including glucose and appetite regulation. Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the treatment of type 2 diabetes since 2005 including exenatide (short- and extended-release), lixisenatide, liraglutide, dulaglutide, albiglutide, and semaglutide. Of these, semaglutide (subcutaneous) and liraglutide are currently US Food and Drug Administration (FDA)-approved for chronic weight management in patients with or without diabetes. The phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program was designed to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with overweight or obesity. Following the submission of the results of the STEP 1-4 trials, the FDA approved once-weekly subcutaneous semaglutide 2.4 mg for chronic weight management in people with overweight or obesity in April 2021. Data from the program demonstrated that semaglutide (2.4 mg once weekly) achieved significant and sustained weight loss, together with improvements in cardiometabolic risk factors compared with placebo, and was generally well tolerated, with a safety profile consistent with other GLP-1RAs. The most common adverse events reported in STEP 1-5 were gastrointestinal events, which were transient, mild-to-moderate in severity, and typically resolved without permanent treatment discontinuation. This article reviews the data from STEP 1-5 and highlights clinically relevant findings for primary care providers.

Cardiometabolic risk factors efficacy of semaglutide in the STEP program.

People with overweight or obesity often suffer from associated cardiometabolic diseases and comorbidities. Current therapies for obesity include lifestyle intervention, bariatric surgery, and pharmacotherapy. The magnitude of weight loss achieved with these therapies can determine the level of improvement in various comorbidities. Once-weekly subcutaneous semaglutide 2.4 mg is a glucagon-like peptide-1 receptor agonist recently approved by the US Food and Drug Administration for the treatment of obesity. This article reviews data from the global phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program, comparing the efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo for weight loss and improvements in cardiometabolic parameters across the STEP 1 to 5 trials. In STEP 1 to 3 and STEP 5, semaglutide led to greater reductions from baseline versus placebo in body weight, waist circumference, body mass index, systolic blood pressure (SBP), and diastolic blood pressure, as well as positive changes in glycated hemoglobin (HbA

Exploring the wider benefits of semaglutide treatment in obesity insight from the STEP program.

Obesity negatively impacts patients health-related quality of life (QOL) and is associated with a range of complications such as type 2 diabetes (T2D), cardiovascular disease, and sleep apnea, alongside decreased physical function, mobility, and control of eating. The Semaglutide Treatment Effect in People with obesity (STEP) trials compared once-weekly subcutaneous semaglutide 2.4 mg with placebo in adults with overweight or obesity, with or without T2D. This article reviews the effects of semaglutide 2.4 mg on QOL, control of eating, and body composition. Weight-related QOL was assessed using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), and health-related QOL was assessed with the 36-item Short Form Health Survey version 2 (SF-36v2®). Control of eating was evaluated using the Control of Eating questionnaire in a subgroup of participants in one trial. Body composition was evaluated via dual-energy x-ray absorptiometry in another trial, in a subgroup of participants with a body mass index of ≤40 kgm

Integrating semaglutide into obesity management - a primary care perspective.

This final article in the supplement aims to summarize a clinical approach for weight management geared toward primary care practitioners, offering practical advice about how to integrate weight management into day-to-day practice. To achieve long-term successful weight loss, a comprehensive multimodal approach is recommended, focusing on both lifestyle modification and appropriate use of therapy. Once-weekly subcutaneous semaglutide 2.4 mg is a novel treatment that can be used as an adjunct to lifestyle modification for the management of overweight and obesity. Key considerations are presented to support its optimal administration in conjunction with lifestyle modification, with a focus on assessing suitability and the importance of dose escalation and monitoring.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke protocol for the pilot study for the SAFER trial.

Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures. SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 21 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective. The London-Central Research Ethics Committee (19LO1597) and Confidentiality Advisory Group (19CAG0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee. ISRCTN72104369.

Rate of glycaemic control and associated factors in patients with type 2 diabetes mellitus treated with insulin-based therapy at selected hospitals in Northwest Ethiopia a multicentre cross-sectional study.

This study was aimed to determine the level of glycaemic control and associated factors in patients with type 2 diabetes mellitus (T2DM) treated with insulin-based therapy. Institutional-based multicentre cross-sectional study design was employed to conduct this study. The diabetes follow-up clinics of selected hospitals in Northwest Ethiopia. Adult patients with T2DM treated with insulin-based therapy at the selected hospitals who met the eligibility criteria were the study participants. Good glycaemic control when fasting blood glucose (FBG) level ranged from 70 to 130 mgdL, and FBG <70 and >130 mgdL was considered poor glycaemic control. A logistic regression model was used to identify determinants of poor glycaemic control. A p<0.05 at 95% CI was statistically significant. Of 403 study participants, 54.8% were males with a mean age of 55.03±10.8 years. Though patients with T2DM were treated with insulin-based therapy, most of the participants (72.5%) could not achieve the target FBG. The overall mean FBG was 177.1±54.3, and far from the target glucose level. Patients who could not practise self-monitoring of blood glucose were found more likely to have poor glycaemic control compared with those who practised self-monitoring (p<0.001). Whereas patients who had a normal body mass index (p0.011) and who were treated with premixed insulin-based therapy (p0.04) were found less likely to have poor glycaemic control compared with patients with obesity and who received NPH insulin based-regimens, respectively. This study demonstrated that a significant proportion of the study samples could not achieve glycaemic targets and the average blood glucose was far higher than the recommended glycaemic target level. Insulin initiation and titration, considering the determinants of glycaemic control, could be recommended to achieve target glycaemic levels.

SPUR psychometric properties of a patient-reported outcome measure of medication adherence in type 2 diabetes.

Poor medication adherence is associated with worsening patient health outcomes and increasing healthcare costs. A holistic tool to assess both medication adherence and drivers of adherence behaviour has yet to be developed. This study aimed to examine SPUR, a multifactorial patient-reported outcome measure of medication adherence in patients living with type 2 diabetes, with a view to develop a suitable model for psychometric analysis.Furthermore, the study aimed to explore the relationship between the SPUR model and socio-clinical factors of medication adherence. The study recruited 378 adult patients living with type 2 diabetes from a mix of community and secondary-care settings to participate in this non-interventional cross-sectional study. The original SPUR-45 tool was completed by participants with other patient-reported outcome measures for comparison, in addition to the collection of two objective adherence measures HbA Factor and reliability analysis conducted on SPUR-45 produced a revised and more concise version (27-items) of the tool, SPUR-27, which was psychometrically assessed. SPUR-27 observed strong internal consistency with significant correlations to the other psychometric measures (Beliefs about Medication Questionnaire, Diabetes Treatment Satisfaction Questionnaire, Medicine Adherence Rating Scale) completed by participants. Higher SPUR-27 scores were associated with lower HbA SPUR-27 demonstrated strong psychometric properties. Further work should look to examine the test-retest reliability of the model as well as examine transferability to other chronic conditions and broader population samples. Overall, the initial findings suggest that SPUR-27 is a reliable model for the multifactorial assessment of medication adherence among patients living with type 2 diabetes.

Diagnosis of coronary artery disease in patients with type 2 diabetes mellitus based on computed tomography and pericoronary adipose tissue radiomics a retrospective cross-sectional study.

Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to cardiovascular disease, and coronary artery disease (CAD) is their leading cause of death. We aimed to assess whether computed tomography (CT) based imaging parameters and radiomic features of pericoronary adipose tissue (PCAT) can improve the diagnostic efficacy of whether patients with T2DM have developed CAD. We retrospectively recruited 229 patients with T2DM but no CAD history (146 were diagnosed with CAD at this visit and 83 were not). We collected clinical information and extracted imaging manifestations from CT images and 93 radiomic features of PCAT from all patients. All patients were randomly divided into training and test groups at a ratio of 73. Four models were constructed, encapsulating clinical factors (Model 1), clinical factors and imaging indices (Model 2), clinical factors and Radscore (Model 3), and all together (Model 4), to identify patients with CAD. Receiver operating characteristic curves and decision curve analysis were plotted to evaluate the model performance and pairwise model comparisons were performed via the DeLong test to demonstrate the additive value of different factors. In the test set, the areas under the curve (AUCs) of Model 2 and Model 4 were 0.930 and 0.929, respectively, with higher recognition effectiveness compared to the other two models (each p < 0.001). Of these models, Model 2 had higher diagnostic efficacy for CAD than Model 1 (p < 0.001, 95% CI 0.129-0.350). However, Model 4 did not improve the effectiveness of the identification of CAD compared to Model 2 (p 0.776) similarly, the AUC did not significantly differ between Model 3 (AUC 0.693) and Model 1 (AUC 0.691, p 0.382). Overall, Model 2 was rated better for the diagnosis of CAD in patients with T2DM. A comprehensive diagnostic model combining patient clinical risk factors with CT-based imaging parameters has superior efficacy in diagnosing the occurrence of CAD in patients with T2DM.

Temporal relationship between atherogenic dyslipidemia and inflammation and their joint cumulative effect on type 2 diabetes onset a longitudinal cohort study.

Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceridehigh-density lipoprotein) in an approximately 4-year exposure period (20062007 to 20102011). After excluding 8824 participants with known diabetes, 43,360 nondiabetic participants were included for further analysis of the T2D outcome. Cox regression models were used to examine the adjusted hazard ratios (aHRs) upon the cumulative hsCRP (CumCRP) and AIP (CumAIP) in the exposure period. In temporal analysis, the adjusted standardized correlation coefficient (β1) of hsCRP20062007 and AIP20102011 was 0.0740 (95% CI, 0.0659 to 0.0820 P < 0.001), whereas the standardized correlation coefficient (β2) of AIP20062007 and hsCRP20102011 was - 0.0293 (95% CI, - 0.0385 to - 0.0201 P < 0.001), which was significantly less than β1 (P < 0.001). During a median follow-up of 7.9 years, 5,118 T2D cases occurred. Isolated exposure to CumAIP or CumCRP was dose-dependently associated with T2D risks, independent of traditional risk factors. Significant interactions were observed between the median CumAIP (- 0.0701) and CumCRP thresholds (1, 3 mgL) (P 0.0308). Compared to CumAIP < - 0.0701 and CumCRP < 1 mgL, those in the same CumAIP stratum but with increasing CumCRP levels had an approximately 1.5-fold higher T2D risk those in higher CumAIP stratum had significantly higher aHRs (95% CIs) 1.64 (1.45-1.86), 1.87 (1.68-2.09), and 2.04 (1.81-2.30), respectively, in the CumCRP < 1, 1 ≤ CumCRP < 3, CumCRP ≥ 3 mgL strata. Additionally, the T2D risks in the co-exposure were more prominent in nonhypertensive, nondyslipidemic, nonprediabetic, or female participants. These findings suggest a stronger association between elevated hsCRP and future AIP changes than vice versa and highlight the urgent need for combined assessment and management of chronic inflammation and atherogenic dyslipidemia in primary prevention, particularly for those with subclinical risks of T2D.

Effect of an electronic reminder of follow-up screening after pregnancy complicated by gestational diabetes mellitus a randomized controlled trial.

To determine the effectiveness of despatching an electronic reminder of participation in screening for gestational diabetes. The reminder was sent to the women 1-8 years after delivery. A registry-based, randomized controlled trial in the North Denmark Region among women with gestational diabetes. Randomization was made, which included seven groups stratified by the childs birth year (2012-2018). The intervention group received standard care supplemented by an electronic reminder through a secure nationwide email system (n 731), while the control group received only standard care (n 732). The primary outcome was based on blood testing for diabetes (OGTT, HbA1c or fasting P-glucose). A total of 471 (32.1%) women participated in screening. The primary outcome was experienced by 257 women (35.1%) in the intervention group and 214 women (29.2%) in the control group. The effect of the reminder seemed to increase with recipients age, non-western origin, urban dwelling, and multiparity. Of those who participated in follow-up screening, 56 (3.8%) were diagnosed with type 2 diabetes. Electronic reminders, based on the principles of informed choice and patient-centred care, to women have been shown to support life-long participation in follow-up screening. Attempts to further stimulation of coverage could however be considered. ISRCTN registry (22042022, ISRCTN23558707).

The role of exercise and hypoxia on glucose transport and regulation.

Muscle glucose transport activity increases with an acute bout of exercise, a process that is accomplished by the translocation of glucose transporters to the plasma membrane. This process remains intact in the skeletal muscle of individuals with insulin resistance and type 2 diabetes mellitus (T2DM). Exercise training is, therefore, an important cornerstone in the management of individuals with T2DM. However, the acute systemic glucose responses to carbohydrate ingestion are often augmented during the early recovery period from exercise, despite increased glucose uptake into skeletal muscle. Accordingly, the first aim of this review is to summarize the knowledge associated with insulin action and glucose uptake in skeletal muscle and apply these to explain the disparate responses between systemic and localized glucose responses post-exercise. Herein, the importance of muscle glycogen depletion and the key glucoregulatory hormones will be discussed. Glucose uptake can also be stimulated independently by hypoxia therefore, hypoxic training presents as an emerging method for enhancing the effects of exercise on glucose regulation. Thus, the second aim of this review is to discuss the potential for systemic hypoxia to enhance the effects of exercise on glucose regulation.

Inequalities in cancer mortality trends in people with type 2 diabetes 20 year population-based study in England.

The aim of this study was to describe the long-term trends in cancer mortality rates in people with type 2 diabetes based on subgroups defined by sociodemographic characteristics and risk factors. We defined a cohort of individuals aged ≥35 years who had newly diagnosed type 2 diabetes in the Clinical Practice Research Datalink between 1 January 1998 and 30 November 2018. We assessed trends in all-cause, all-cancer and cancer-specific mortality rates by age, gender, ethnicity, socioeconomic status, obesity and smoking status. We used Poisson regression to calculate age- and calendar year-specific mortality rates and Joinpoint regression to assess trends for each outcome. We estimated standardised mortality ratios comparing mortality rates in people with type 2 diabetes with those in the general population. Among 137,804 individuals, during a median follow-up of 8.4 years, all-cause mortality rates decreased at all ages between 1998 and 2018 cancer mortality rates also decreased for 55- and 65-year-olds but increased for 75- and 85-year-olds, with average annual percentage changes (AAPCs) of -1.4% (95% CI -1.5, -1.3), -0.2% (-0.3, -0.1), 1.2% (0.8, 1.6) and 1.6% (1.5, 1.7), respectively. Higher AAPCs were observed in women than men (1.5% vs 0.5%), in the least deprived than the most deprived (1.5% vs 1.0%) and in people with morbid obesity than those with normal body weight (5.8% vs 0.7%), although all these stratified subgroups showed upward trends in cancer mortality rates. Increasing cancer mortality rates were also observed in people of White ethnicity and formercurrent smokers, but downward trends were observed in other ethnic groups and non-smokers. These results have led to persistent inequalities by gender and deprivation but widening disparities by smoking status. Constant upward trends in mortality rates were also observed for pancreatic, liver and lung cancer at all ages, colorectal cancer at most ages, breast cancer at younger ages, and prostate and endometrial cancer at older ages. Compared with the general population, people with type 2 diabetes had a more than 1.5-fold increased risk of colorectal, pancreatic, liver and endometrial cancer mortality during the whole study period. In contrast to the declines in all-cause mortality rates at all ages, the cancer burden has increased in older people with type 2 diabetes, especially for colorectal, pancreatic, liver and endometrial cancer. Tailored cancer prevention and early detection strategies are needed to address persistent inequalities in the older population, the most deprived and smokers.

Development and validation of a nomogram model for individualized prediction of hypertension risk in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) with hypertension (DH) is the most common diabetic comorbidity. Patients with DH have significantly higher rates of cardiovascular disease morbidity and mortality. The objective of this study was to develop and validate a nomogram model for the prediction of an individuals risk of developing DH. A total of 706 T2DM patients who met the criteria were selected and divided into a training set (n 521) and a validation set (n 185) according to the discharge time of patients. By using multivariate logistic regression analysis and stepwise regression, the DH nomogram prediction model was created. Calibration curves were used to evaluate the models accuracy, while decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to evaluate the models clinical applicability and discriminatory power. Age, body mass index (BMI), diabetic nephropathy (DN), and diabetic retinopathy (DR) were all independent risk factors for DH (P < 0.05). Based on independent risk factors identified by multivariate logistic regression, the nomogram model was created. The model produces accurate predictions. If the total nomogram score is greater than 120, there is a 90% or higher chance of developing DH. In the training and validation sets, the models ROC curves are 0.762 (95% CI 0.720-0.803) and 0.700 (95% CI 0.623-0.777), respectively. The calibration curve demonstrates that there is good agreement between the models predictions and the actual outcomes. The decision curve analysis findings demonstrated that the nomogram model was clinically helpful throughout a broad threshold probability range. The DH risk prediction nomogram model constructed in this study can help clinicians identify individuals at high risk for DH at an early stage, which is a guideline for personalized prevention and treatments.

Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases Systematic review and meta-analysis.

Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations. A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models. Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for overall cardiovascular disease (fatal and non-fatal) (hazard ratio HR 1.68, 95% confidence interval CI 1.33-2.12 I QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.

Opposing Roles of Sphingosine 1-Phosphate Receptors 1 and 2 in Fat Deposition and Glucose Tolerance in Obese Male Mice.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates fundamental cellular processes such as proliferation, migration, apoptosis, and differentiation through 5 cognate G protein-coupled receptors (S1P1-S1P5). We previously demonstrated that blockade of S1P2 signaling in S1P2-deficient mice attenuates high-fat diet-induced adipocyte hypertrophy and glucose intolerance and an S1P2-specific antagonist JTE-013 inhibits, whereas an S1P1S1P3 dual antagonist (VPC23019) activates, adipogenic differentiation of preadipocytes. Based on those observations, this study examined whether an S1P1-specific agonist, SEW-2871, VPC23019, or their combination acts on obesity and glucose intolerance in leptin-deficient obob mice. The oral administration of SEW-2871 or JTE-013 induced significant reductions in bodyepididymal fat weight gains and epididymalinguinal fat adipocyte sizes and improved glucose intolerance and adipocyte inflammation in obob mice but not in their control C57BL6J mice. Both SEW-2871 and JTE-013 decreased messenger RNA levels of tumor necrosis factor-α and CD11c, whereas they increased those of CD206 and adiponectin in the epididymal fats isolated from obob mice with no changes in the levels of peroxisome proliferator activated receptor γ and its regulated genes. By contrast, VPC23019 did not cause any such alterations but counteracted with all those SEW-2871 actions in these mice. In conclusion, the S1P1 agonist SEW-2871 acted like the S1P2 antagonist JTE-013 to reduce bodyepididymal fats and improve glucose tolerance in obese mice. Therefore, this study raises the possibility that endogenous S1P could promote obesitytype 2 diabetes through the S1P2, whereas exogenous S1P could act against them through the S1P1.

Sex differences in islet stress responses support female β cell resilience.

Pancreatic β cells play a key role in maintaining glucose homeostasis dysfunction of this critical cell type causes type 2 diabetes (T2D). Emerging evidence points to sex differences in β cells, but few studies have examined male-female differences in β cell stress responses and resilience across multiple contexts, including diabetes. Here, we address the need for high-quality information on sex differences in β cell and islet gene expression and function using both human and rodent samples. We compared β cell gene expression and insulin secretion in donors with T2D to non-diabetic donors in both males and females. In mice, we generated a well-powered islet RNAseq dataset from 20-week-old male and female siblings with similar insulin sensitivity. Our unbiased analysis of murine gene expression pointed to a sex difference in the endoplasmic reticulum (ER) stress response. Based on this analysis, we hypothesize female islets will be more resilient to ER stress than male islets. To test this, we subjected islets isolated from age-matched male and female mice to thapsigargin treatment and monitored protein synthesis, cell death, and β cell insulin production and secretion. Transcriptomic and proteomic analyses were used to characterize sex differences in islet responses to ER stress. Our single-cell analysis of human β cells revealed sex-specific changes to gene expression and function in T2D, correlating with more robust insulin secretion in human islets isolated from female donors with T2D compared to male donors with T2D. In mice, RNA sequencing revealed differential enrichment of unfolded protein response pathway-associated genes, where female islets showed higher expression of genes linked with protein synthesis, folding, and processing. This differential expression was biologically significant, as islets isolated from female mice were more resilient to ER stress induction with thapsigargin. Specifically, female islets showed a greater ability to maintain glucose-stimulated insulin production and secretion during ER stress compared with males. Our data demonstrate sex differences in β cell gene expression in both humans and mice, and that female β cells show a greater ability to maintain glucose-stimulated insulin secretion across multiple physiological and pathological contexts.

Differences in the Clinical Outcome of Ischemic and Nonischemic Cardiomyopathy in Heart Failure With Concomitant Opioid Use Disorder.

Heart Failure (HF) and Opioid Use Disorder (OUD) independently have significant impact on patients and the United States (US) health system. In the setting of the opioid epidemic, research on the effects of OUD on cardiovascular diseases is rapidly evolving. However, no study exists on differential outcomes of ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) in patients with HF with OUD. We performed a retrospective, observational cohort study using National Inpatient Sample (NIS) 2018-2020 databases. Patients aged 18 years and above with diagnoses of HF with concomitant OUD were included. Patients were further classified into ICM and NICM. Primary outcome of interest was differences in all- cause in-hospital mortality. Secondary outcome was incidence of cardiogenic shock. We identified 99,810 hospitalizations that met inclusion criteria, ICM accounted for 27%. Mean age for ICM was higher compared to NICM (63 years vs 56 years, P < 0.01). Compared to NICM, patients with ICM had higher cardiovascular disease risk factors and comorbidities type 2 diabetes mellitus (46.3 % vs 30.1%, P < 0.01), atrial fibrillationflutter (33.5% vs 29.9%, P < 0.01), hyperlipidemia (52.5% vs 28.9%, P < 0.01), and Charlson comorbidity index ≥5 was 46.7% versus 29.7%, P < 0.01. After controlling for covariates and potential confounders, we observed higher odds of all-cause in-hospital mortality in patients with NICM (aOR 1.36 95% CI1.03-1.78, P 0.02). There was no statistical significant difference in incidence of cardiogenic shock between ICM and NICM (aOR 0.8695% CI 0.70-1.07, P 0.18). In patients with HF with concomitant OUD, we found a 36% increase in odds of all-cause in-hospital mortality in patients with NICM compared to ICM despite being younger in age with less comorbidities. There was no difference in odds of in-hospital cardiogenic shock in this study population. This study contributes to the discussion of OUD and cardiovascular diseases which is rapidly developing and requires further prospective studies.

Association of circadian rest-activity rhythms with cardiovascular disease and mortality in type 2 diabetes.

To examine the associations of disrupted circadian rest-activity rhythm (CRAR) with cardiovascular diseases and mortality among people with type 2 diabetes. A total of 3147 participants with baseline type 2 diabetes (mean age 65.21 years, 39.78% female mean HbA1c 50.02 mmolmol) from UK Biobank were included. The following CRAR parameters were derived from acceleration data interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), most active 10 h period onset (M10 onset), and least active 5 h period onset (L5 onset). We used Cox proportional hazards models to estimate the associations of CRAR with cardiovascular diseases and mortality, adjusting for sociodemographic, lifestyle, and health characteristics. Participants in the lowest quartile of IS and RA exhibited the greatest risk of developing cardiovascular disease (IS, hazard ratio HR Objectively determined CRAR disturbances may increase the risk of cardiovascular diseases and mortality among people with type 2 diabetes.

Association of type 2 diabetes with coronary risk factors, clinical presentation, angiography, coronary interventions and follow-up outcomes A single centre prospective registry.

To determine variations in coronary artery disease (CAD) clinical presentation, interventions, and outcomes in patients with diabetes vs without, a prospective study was performed. Successive patients with predominantly acute coronary syndromes who underwent percutaneous coronary intervention (PCI) were enrolled from January 2018 to March 2021. Patients with diabetes were compared to those without diabetes to determine differences in clinical and angiographic features and outcomes. In-person and telephonic follow-up were performed. Primary outcome was cardiovascular death and co-primary were major adverse cardiovascular events (cardiovascular death, myocardial infarction, revascularization, stroke). Cox-proportional hazard ratios (HR) and 95% confidence intervals (CI) were calculated. 5181 patients (men 4139,women 1042) were enrolled. Acute coronary syndrome(ACS) was in 4917 (94.9%) and diabetes in 1987 (38.4%). Patients with diabetes were older (61.1 ± 9.6 vs 59.7 ± 11.5years), with more hypertension (71.1 vs 45.5%), chronic kidney disease (3.0 vs 1.7%), previous PCI (13.5 vs 11.0%), past coronary artery bypass graft surgery (4.9 vs 2.4%), non ST-elevation myocardial infarction (59.6 vs 51.6%) and triple vessel disease (20.3 vs 17.2%) (p < 0.01). Duration of hospitalization was more in diabetes (4.2 ± 2.6 vs 4.0 ± 2.1 days, p 0.023) with no difference in in-hospital deaths (1.4 vs 1.0%, p 0.197). Follow up was performed in 1202 patients (diabetes 499,41.5%) enrolled from April 2020 to March 2021 (median 16.4 months). In diabetes there were more cardiovascular deaths (multivariate adjusted HR 2.38, CI 1.13-5.02) and all-cause deaths (HR 1.85, CI 1.06-3.22). CAD patients with diabetes undergoing PCI have more hypertension, chronic kidney disease, non ST-elevation myocardial infarction and triple vessel disease. At medium-term follow-up the incidence of cardiovascular and all-cause deaths is significantly more in these patients.

Effects of social isolation on the cognitive status of people over 65 years of age during the SARS-CoV-2 pandemic A longitudinal comparative study.

Introduction The SARS-CoV-2 pandemic has affected the entire population, especially vulnerable people with risk factors, such as people over 65 years. Globally and nationally, health protection measures were established to reduce transmission and the impact of the disease on the healthcare system, such as using face masks, hand washing, and social distancing, among others. This led to restrictions on activities outside the home, which affected the cognitive sphere of the population, especially people over 65 years of age. Objective To demonstrate that social isolation causes changes in the cognitive status of people over 65 years of age. Methods A longitudinal study was conducted from 2019 to 2020, with the participation of 37 older adults in a parish club of support activities who voluntarily agreed to participate by signing the informed consent form. The Folstein Mini-Mental State Examination was administered to all of them at two points in the study before the pandemic and after six months of strict social isolation established as a control measure for the SARS-CoV-2 pandemic. We looked for cognitive status differences during this period and studied qualitative-quantitative sociodemographic variables. Results The club members were older people, predominantly women. Mean age of the participants was 75.4 years 89.2% had little schooling (less than ten years of formal education). Identified prevalent diseases were arterial hypertension and type-2 diabetes mellitus. In the first evaluation, six out of thirty-seven participants had slight cognitive deficits (16.2%), all females there were no cases of cognitive impairment the rest had normal cognitive status (31 out of 37, or 83.8%). After the second evaluation (at the end of strict isolation due to the pandemic), we observed that 11 (29.7%) participants had slight cognitive deficits (ten female and one male), which represents an increase of 13.5%. In addition, four participants (10.8%) showed mild cognitive impairment, all females. Such changes were statistically significant (p-value < 0.05). We conclude that social isolation due to the SARS-CoV-2 pandemic was related to changes in the cognitive status of the elderly. Introducción La pandemia por SARS-CoV-2, ha afectado a toda la población, especialmente a personas vulnerables y con factores de riesgo, como las personas mayores de 65 años. A nivel mundial y nacional se establecieron medidas de protección sanitaria como medio para reducir la transmisión y el impacto de la enfermedad en el sistema de salud como uso de mascarilla, lavado de manos, distanciamiento social, entre otros. Esto generó restricciones en las actividades fuera del hogar, lo que afectó el aspecto cognitivo de la población, especialmente a las personas mayores de 65 años. Objetivo Demostrar que el aislamiento social genera cambios en el estado cognitivo de las personas mayores de 65 años. Metodología Se realizó un estudio longitudinal en el periodo de 2019 a 2020, con la participación de 37 personas mayores pertenecientes a un club parroquial de actividades de apoyo, quienes aceptaron participar voluntariamente mediante firma del consentimiento informado. A todos se les aplicó el en dos momentos del estudio previo a la pandemia y al cabo de seis meses del aislamiento social estricto establecido como medida de control de la pandemia por SARS- CoV-2. En dicho período se buscaron diferencias en el estado cognitivo y también se estudiaron variables sociodemográficas cuali-cuantitativas. Resultados Los integrantes del club son personas mayores, predominantemente mujeres. El promedio de edad de los participantes fue de 75,4 años el 89,2% tenía escolaridad baja (menos de 10 años de educación). Las enfermedades prevalentes identificadas fueron hipertensión arterial y diabetes mellitus tipo-2. En la primera evaluación se observó que 6 de 37 participantes presentaron ligero déficit cognitivo (16,2%), todas de sexo femenino no hubo casos con deterioro cognitivo los demás tuvieron estado cognitivo normal (31 de 37, es decir 83,8%). Tras la segunda evaluación (al finalizar el aislamiento estricto por la pandemia), se observó que 11 (29,7%) personas registraron ligero déficit cognitivo (10 mujeres y 1 hombre), lo que implica un incremento de 13,5%. Además, se identificaron cuatro casos (10,8%) de los participantes que presentaron deterioro cognitivo leve, todas fueron de sexo femenino. Tales cambios fueron estadísticamente significativos (valor p < 0,05). Se concluye que el aislamiento por la pandemia de SARS-CoV-2 está relacionado con cambios en el estado cognitivo de las personas mayores.

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice.

Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO). Transient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography-based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining. Compared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 ( DM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.

Association of metformin use and survival in patients with cutaneous melanoma and diabetes.

Metformin use has been associated with improved survival in patients with different types of cancer, but research regarding the effect of metformin on cutaneous melanoma (CM) survival is sparse and inconclusive. To investigate the association between metformin use and survival among patients with CM and diabetes. All adult patients with a primary invasive CM between 2007 and 2014 were identified in the Swedish Melanoma Registry and followed until death, or end of follow-up on 31 December 2017 in this population-based cohort study. Patients with both CM and type 2 diabetes mellitus were assessed further. Overall survival (OS) and melanoma-specific survival (MSS) were the primary endpoints. Cox proportional hazard models estimating crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used comparing peridiagnostic use vs. nonuse of metformin. Dose response was evaluated based on defined daily doses. Among a total of 23 507 patients, 1162 patients with CM and type 2 diabetes mellitus were included in the final cohort, with a median follow-up time of 4.1 years (interquartile range 2.4-6.1). Peridiagnostic metformin use was associated with a significantly decreased risk of death by any cause (HR 0.68, 95% CI 0.57-0.81). Cumulative pre- and postdiagnostic metformin use was also associated with improved OS the HR for prediagnostic use was 0.90 (95% CI 0.86-0.95) for every 6 months of use and the HR for postdiagnostic use ranged from 0.98 (95% CI 0.97-0.98) for 0-6 months to 0.59 (0.49-0.70) for 24-30 months of use. No association was found for metformin use and MSS. Metformin use was associated with improved OS in patients with CM and diabetes regardless of timing (pre-, post- or peridiagnostic use) and followed a dose-response pattern. However, further research regarding the underlying mechanisms is warranted.

Remember Diabetes Mellitus When Assessing Renal Blood Flow in Hypertensive Patients A Renal Frame Count Study.

Diabetes mellitus (DM) progresses with dynamic changes in renal blood flow and glomerular filtration. Renal frame count (RFC) is a cineangiographical parameter that is capable of presenting microvascular and macrovascular changes in the renal blood flow. We aimed to show the changes, which may be caused by DM in the perfusion, by using RFC. Totally 110 hypertensive subjects consisting of 55 DM patients and 55 non-DM patients as a control group who underwent renal angiography were retrospectively enrolled in the study. The RFC values of all subjects were calculated and compared to each other. There were no significant differences between the two groups in terms of basal demographic characteristics and antihypertensive medications. The RFC value measured from the left renal artery was significantly lower in the DM group compared to the control group. (11.33±2.55, 13.49±3.24, respectively p<0.001). The RFC value measured the right renal artery was detected to be significantly lower in the DM group than the control group (11.07±2.43, 13.33±3.07, respectively p<0.001). The mean RFC value was also significantly lower in the DM group compared to the control group (11.20±2.18, 13.41±2.84, respectivelyp<0.001). In the multivariable linear regression analysis conducted to determine the variables which may affect mean RFC, it was determined that only the HbA1C level had a relation with the mean RFC value. To the best of our knowledge, this is the first study to show the influence of DM on RFC. RFC seems to decrease in DM subjects.

Adherence to the EAT-Lancet diet is associated with a lower risk of type 2 diabetes the Danish Diet, Cancer and Health cohort.

Type 2 diabetes is a global health problem. While a healthy diet lowers risk of type 2 diabetes, less is known about diets with low climate impact. This study aimed to investigate adherence to the EAT-Lancet diet and risk of type 2 diabetes in a Danish setting. In the Danish Diet, Cancer and Health cohort, dietary data were collected using a validated 192-item food frequency questionnaire, at recruitment in 1993-1997. In total, 54,232 participants aged 50-64 years at baseline with no previous cancer or diabetes diagnoses were included in the current analyses. The EAT-Lancet diet score was used to assess adherence to the EAT-Lancet diet. Participants scored 0 (non-adherence) or 1 (adherence) point for each of the 14 dietary components of the diet score (range 0-14 points). Participants were followed through register linkage until type 2 diabetes diagnosis or censoring. Hazard ratios and 95% confidence intervals (CI) were estimated using multivariable-adjusted Cox regression models. During a median 15-year follow-up period, 7130 participants developed type 2 diabetes. The hazard ratio for developing type 2 diabetes was 0.78 (95% CI 0.71 0.86) for those with highest EAT-Lancet diet scores (11-14 points) compared to those with lowest scores (0-7 points) after adjusting for potential confounders. After further adjusting for potential mediators, including BMI, the corresponding hazard ratio was 0.83 (95% CI 0.76 0.92). Greater adherence to the EAT-Lancet diet was associated with a lower risk of developing type 2 diabetes in a middle-aged Danish population.

Tirzepatide for Weight Loss Can Medical Therapy Outweigh Bariatric Surgery

The worldwide prevalence of obesity has been increasing progressively over the past few decades and is predicted to continue to rise in coming years. Unfortunately, this epidemic is also affecting increasing rates of children and adolescents, posing a serious global health concern. Increased adiposity is associated with various comorbidities and increased mortality risk. Conversely, weight loss and chronic weight management are associated with improvements in overall morbidity and mortality. The pathophysiology of obesity is multifactorial with complex interactions between genetic and environmental factors. The foundation of most weight loss plans is lifestyle modification including dietary change and exercise. However, lifestyle modification alone is often insufficient to achieve clinically meaningful weight loss due to physiological mechanisms that limit weight reduction and promote weight regain. Therefore, research has focused on adjunctive pharmacotherapy to enable patients to achieve greater weight loss and improved chronic weight maintenance compared to lifestyle modification alone. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin hormone analogs that have proven effective for the management of type 2 diabetes mellitus as well as obesity and overweight. Tirzepatide is a novel twincretin that functions as a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA. Tirzepatide was recently approved by the Food and Drug Administration for the management of type 2 diabetes. Similar to previously approved GLP-1RAs, weight loss is a common side effect of tirzepatide which prompted research focused on its use as a primary weight loss therapy. Although this drug has not yet been approved as an antiobesity medication, there are several phase 3 clinical trials that have demonstrated superior weight loss efficacy compared with previously approved medications. This review article will discuss the discovery and mechanism of tirzepatide, as well as the completed and ongoing trials that may lead to its approval as an adjunctive pharmacotherapy for weight loss.

Adjunctive Probio-X Treatment Enhances the Therapeutic Effect of a Conventional Drug in Managing Type 2 Diabetes Mellitus by Promoting Short-Chain Fatty Acid-Producing Bacteria and Bile Acid Pathways.

Metformin is a common drug for the management of type 2 diabetes mellitus however, it causes various adverse gastrointestinal effects, especially after prolonged treatment. It is thus of interest to identify an adjuvant treatment that synergizes with the efficacy of metformin while mitigating its adverse effects. Since previous evidence supports that the gut microbiota is a target of metformin, this study investigated the beneficial effect and mechanism of the coadministration of probiotics with metformin in the management of type 2 diabetes mellitus by conducting a 3-month randomized, double-blind, placebo-controlled clinical trial (

Relationship between circulating senescence-associated secretory phenotype levels and severity of type 2 diabetes-associated periodontitis A cross-sectional study.

Senescence-associated secretory phenotype (SASP) has recently been found to drive comorbid diabetes and periodontitis by inducing a chronic, low-degree inflammatory state. Here, we sought to explore the relationship between circulating SASP and the severity of type 2 diabetes-associated periodontitis (DP). Eighty patients (middle-aged periodontitis, M-P group aged periodontitis, A-P group M-DP group and A-DP group n 20) provided gingival epithelium, serum, and periodontal clinical parameters. Circulating levels of 12 DP-related SASP factors were analyzed by immunoassay. Correlation between periodontal clinical parameters and circulating SASP levels was analyzed by Spearmans rank correlation coefficient and back propagation artificial neural network (BPNN). Senescence markers (p16, p21, and HMGB1) in gingiva were determined by immunofluorescence assay. M-DP group had increased serum levels of twelve SASP factors compared with the M-P group (p < 0.5). Serum levels of IL-6, IL-4, and RAGE were higher in the A-DP group than the A-P group (p < 0.5). The circulating concentrations of certain SASP proteins, including IL-1β, IL-4, MMP-8, OPG, RANKL, and RAGE were correlated with the clinical parameters of DP. BPNN showed that serum SASP levels had considerable predictive value for CAL of DP. Additionally, the DP group had higher expressions of p16, p21, and cytoplasmic-HMGB1 in the gingiva than the P group (p < 0.5). Significantly enhanced circulating SASP levels and aggravated periodontal destruction were observed in patients with DP. Importantly, a non-negligible association between serum SASP levels and the severity of DP was found.

A case of esophageal histoplasmosis mimicking carcinoma on endoscopy.

A 54-year-old woman with progressive and non-acute dysphagia to solid foods, post-feeding vomiting, and weight loss of 10 kg in 1 year. As personal history, she was a former smoker of 60 pack-year, heart transplant for idiopathic dilated cardiomyopathy, and type 2 diabetes. She was on daily use of metformin and immunosuppressive drugs. The laboratory tests were all normal. Upper digestive endoscopy (UDE) revealed in the middle third of the esophagus a lesion of 3 cm presenting atypical rectified vessels, covering 50% of the esophageal lumen, suggestive type 0-IIcIIa1 (A). The chromoendoscopy with Lugol iodine at 1.25% showed a positive pink sign (B). Biopsies showed esophagitis with mixed inflammatory infiltrate and numerous macrophages (C-upper panel). The Periodic Acid-Schiff staining showed small yeasts compatible with Histoplasma capsulatum, measuring 0.5 to 2.5 µm, within the cytoplasm of macrophages (arrows), with a clear halo (inset, arrows) (C-lower panel). These findings were compatible with esophageal histoplasmosis. Treatment was started with oral Itraconazole 400mgday. After 3 months, a new UDE with biopsies showed complete esophageal healing. Gastrointestinal histoplasmosis manifests mainly in the small bowel and colon, related to a great amount of lymphoid tissue in these areas. Patients can present with fever, weight loss, abdominal pain and diarrhea. In endoscopy, we may find ulcerations, thickened wall, plaques and pseudopolyps2. It is considered a rare condition, and in only 3% of cases, there is esophageal involvement. This manifestation is mainly in immunosuppressed patients. It can be related to direct involvement of the esophagus or secondary to infiltration of mediastinal nodes2. In endoscopy, ulcerations, inflammatory masses, strictures, and external compressions can be found. This case illustrated the difficulty in differentiating early cancer from an esophageal histoplasmosis.

Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes Phase 1 Results.

Background Blockade of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a potentially attractive mechanism for lowering inflammatory and lipid risk in patients with atherosclerosis. This study aims to assess the safety, tolerability, and target engagement of MEDI6570, a high-affinity monoclonal blocking antibody to LOX-1. Methods and Results This phase 1, first-in-human, placebo-controlled study (NCT03654313) randomized 88 patients with type 2 diabetes to receive single ascending doses (10, 30, 90, 250, or 500 mg) or multiple ascending doses (90, 150, or 250 mg once monthly for 3 months) of MEDI6570 or placebo. Primary end point was safety secondary and exploratory end points included pharmacokinetics, immunogenicity, free soluble LOX-1 levels, and change in coronary plaque volume. Mean age was 57.658.1 years in the single ascending dosesmultiple ascending doses groups, 31.3%62.5% were female, and mean type 2 diabetes duration was 9.78.7 years. Incidence of adverse events was similar among cohorts. MEDI6570 exhibited nonlinear pharmacokinetics, with terminal half-life increasing from 4.6 days (30 mg) to 11.2 days (500 mg), consistent with target-mediated drug disposition. Dose-dependent reductions in mean soluble LOX-1 levels from baseline were observed (>66% at 4 weeks and 71.61-82.96% at 10 weeks in the single ascending doses and multiple ascending doses groups, respectively). After 3 doses, MEDI6570 was associated with nonsignificant regression of noncalcified plaque volume versus placebo (-13.45 mm

The interaction of T2DM and BMI with NASH in recipients of liver transplants an SRTR database analysis.

NASH-related liver transplants are increasing because of the obesity epidemic, but the influence of T2DM on various levels of BMI among NASH recipients is unclear. We analyzed data retrieved from SRTR on 4,515 patients. We divided patients by BMI into five groups normal weight overweight class 1 obesity class 2 obesity and class 3 obesity. Statistical analysis was done. Patients in the NASH group with T2DM had a lower patient and graft survival than patients without T2DM (5-year patient and graft survival 77.5% vs. 79.8% Our research reveals that the focus of the post-transplantation treatment should be different for different BMI patients.

Dietary management of adults with type 2 diabetes and the role of the nurse.

Dietary strategies for the management of patients with type 2 diabetes can be effective in maintaining glycaemic control. In some cases, the use of specific and supervised dietary strategies can result in remission of the condition. Despite this, the use of anti-diabetes medicines remains the prevailing focus of treatment guidelines. Nurses in primary care are involved in all aspects of management of patients with type 2 diabetes, including advising on lifestyle changes such as diet. This article considers some of the barriers and enablers to dietary management of patients with type 2 diabetes and offers practical advice that nurses can share with their patients. The author also discusses remission of type 2 diabetes and the dietary approaches used to achieve this.

Dynamic response of red blood cells in health and disease.

The viscoelastic response of the red blood cells (RBCs) affected by hematological disorders become severely impaired by the altered biophysical and morphological properties. These include traits like reduced deformability, increased membrane viscosity, and change in cell shape, causing substantial changes in the overall hemodynamics. RBCs, by virtue of their highly elastic membrane and low bending rigidity, exhibit complex dynamics when exposed to cyclic, transient forces in the microcirculation. Here, we employ mesoscopic numerical simulations based on the dissipative particle dynamics (DPD) framework to explore the dynamics of healthy, schizont stage malaria-infected and type 2 diabetes mellitus affected RBCs subjected to external time-dependent loads. The paper focuses on the imposition and cessation of external forcing on the cells of two different typologies, saw-tooth cyclic wave loading and sudden loads in the form of creep and relaxation phenomena. The effects of varying the rate of stress and the applied stress magnitude were investigated. Our simulations disclosed unique shape transitions of the hysteresis curves at varied loading rates. A careful analysis reveals a critical threshold of half cycle time of the from wherein the deformation of all cells observed, healthy or otherwise, falls under the nearly reversible deformation regime displaying minimal energy dissipation. Finally, we also examined the individual effects of the different constitutive and geometric characteristics attributed to the pathological cells and observed interesting recovery dynamics of spherocytes and cells having high shear moduli. The distinguished deformation behaviour of healthy and diseased cells could establish external force as a valuable initial biomarker.

Abnormal functional connectivity of the frontostriatal circuits in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with an increased incidence of cognitive and emotional disorders. Previous studies have indicated that the frontostriatal circuits play a significant role in brain disorders. However, few studies have investigated functional connectivity (FC) abnormalities in the frontostriatal circuits in T2DM. We aimed to investigate the abnormal functional connectivity (FC) of the frontostriatal circuits in patients with T2DM and to explore the relationship between abnormal FC and diabetes-related variables. Twenty-seven patients with T2DM were selected as the patient group, and 27 healthy peoples were selected as the healthy controls (HCs). The two groups were matched for age and sex. In addition, all subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological evaluation. Seed-based FC analyses were performed by placing six bilateral pairs of seeds within Patients with T2DM showed abnormalities in the FC of the frontostriatal circuits. Our findings show significantly reduced FC between the right caudate nucleus and left precentral gyrus (LPCG) in the patients with T2DM compared to the HCs. The FC between the prefrontal cortex (left inferior frontal gyrus, left frontal pole, right frontal pole, and right middle frontal gyrus) and the right caudate nucleus has a significant positive correlation with fasting blood glucose (FBG). The results showed abnormal FC of the frontostriatal circuits in T2DM patients, which might provide a new direction to investigate the neuropathological mechanisms of T2DM.

Immunohistochemical Localization of Alogliptin, a DPP-4 Inhibitor, in Tissues of Normal and Type 2 Diabetes Model Rat.

We investigated the pharmacokinetics of alogliptin (AG) at the cell and tissue level in healthy Wistar rats and a type 2 diabetic Goto-Kakizaki (GK) rat model. Immunohistochemistry of the renal tissue in these rats, post 1 hr of AG administration, showed that the signal was observed in the glomeruli, proximal tubule S3 segments, distal tubules, collecting ducts, and only in the brush border of the epithelial cells of the proximal tubule S1, S2 segments. After 6 hr of AG administration, the staining intensity of the regions other than the S3 segments was considerably reduced in Wistar rats, with no change observed in GK rats. At 24 hr, the staining intensity was considerably reduced, even in GK rats however, the staining of the S3 segment remained unaltered in both. Hepatocytes in zone III of the hepatic lobule were more intensely stained than those in zone I in Wistar rats at 1 hr. However, almost no staining was observed in the hepatocytes of GK rats at 1 hr. Complete loss of signal was observed in the hepatocytes of the Wistar rats after 6 hr. This study revealed that the pharmacokinetics of AG in GK rats are different from those in Wistar rats.

Clinical implications of COVID-19 in patients with metabolic-associated fatty liver disease.

People across the world are affected by the coronavirus disease 2019 (COVID-19), brought on by the SARS-CoV type-2 coronavirus. Due to its high incidence in individuals with diabetes, metabolic syndrome, and metabolic-associated fatty liver disease (MAFLD), COVID-19 has gained much attention. The metabolic syndromes hepatic manifestation, MAFLD, carries a significant risk of type-2-diabetes. The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic. Independent of the metabolic syndrome, MAFLD may impact the severity of the viral infections, including COVID-19 or may even be a risk factor. An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics. Many liver markers are seen elevated in COVID-19. MAFLD patients with associated comorbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension, and old age are prone to develop severe disease. There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19. The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19. This review investigates the implications of COVID-19 on liver injury and disease severity and vice-versa. We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.

Association between inflammation, lipopolysaccharide binding protein, and gut microbiota composition in a New Hampshire Bhutanese refugee population with a high burden of type 2 diabetes.

South Asian refugees experience a high risk of obesity and diabetes yet are often underrepresented in studies on chronic diseases and their risk factors. The gut microbiota and gut permeability, as assessed through circulating lipopolysaccharide binding protein (LBP), may underlie the link between chronic inflammation and type 2 diabetes (T2D). The composition of the gut microbiota varies according to multiple factors including demographics, migration, and dietary patterns, particularly fiber intake. However, there is no evidence on the composition of the gut microbiota and its relationship with metabolic health in refugee populations, including those migrating to the United States from Bhutan. The objective of this study was to examine glycemic status in relation to LBP, systemic inflammation fiber intake, and gut microbiota composition in Bhutanese refugee adults residing in New Hampshire ( This cross-sectional study included a convenience sample of Bhutanese refugee adults ( We identified a substantial chronic disease burden in this study population, and observed a correlation between glycemic status, LBP, and inflammation, and a correlation between glycemic status and gut microbiome alpha diversity. Further, we identified a significant correlation between proinflammatory taxa and inflammatory cytokines. SCFA-producing taxa were found to be inversely correlated with age. To date, this is the most comprehensive examination of metabolic health and the gut microbiome in a Bhutanese refugee population in NH. The findings highlight areas for future investigations of inflammation and glycemic impairment, in addition to informing potential interventions targeting this vulnerable population.

Relationship between changes in microbiota induced by resveratrol and its anti-diabetic effect on type 2 diabetes.

Although a general healthy gut microbiota cannot be defined due to numerous internal and external individual factors, such as sex, age, ethnicity, genetics, environment, diet and drugs affect its composition, certain microbial species and gut microbiota compositions seem to be related to the progression of insulin resistance to type 2 diabetes, as well as the development of microvascular and macrovascular complications of diabetes. The present review aimed at gathering the reported information describing how resveratrol induced changes in microbiota composition can mediate the positive effects of this polyphenol on glucose homeostasis under type 2 diabetic conditions, both in animals and humans. Based on the fact that some changes observed in the gut microbiota of type 2 diabetic animals and patients are reversed by resveratrol treatment, and taking into account that some resveratrol mediated changes in gut microbiota composition are similar to those induced by anti-diabetic drugs such as metformin, it can be proposed that four genera,

MOTS-c repairs myocardial damage by inhibiting the CCN1ERK12EGR1 pathway in diabetic rats.

Cardiac structure remodeling and dysfunction are common complications of diabetes, often leading to serious cardiovascular events. MOTS-c, a mitochondria-derived peptide, regulates metabolic homeostasis by accelerating glucose uptake and improving insulin sensitivity. Plasma levels of MOTS-c are decreased in patients with diabetes. MOTS-c can improve vascular endothelial function, making it a novel therapeutic target for the cardiovascular complications of diabetes. We investigated the effects of MOTS-c on cardiac structure and function and analyzed transcriptomic characteristics in diabetic rats. Our results indicate that treatment with MOTS-c for 8-week repaired myocardial mitochondrial damage and preserved cardiac systolic and diastolic function. Transcriptomic analysis revealed that MOTS-c altered 47 disease causing genes. Functional enrichment analysis indicated MOTS-c attenuated diabetic heart disease involved apoptosis, immunoregulation, angiogenesis and fatty acid metabolism. Moreover, MOTS-c reduced myocardial apoptosis by downregulating CCN1 genes and thereby inhibiting the activation of ERK12 and the expression of its downstream EGR1 gene. Our findings identify potential therapeutic targets for the treatment of T2D and diabetic cardiomyopathy.

Type 2 diabetes mellitus (T2DM) is a metabolic disease that has led to a significant global public health burden. In this work, we investigated the effects of We found that 10 The supplementation of Hao9 improved gut microbiota, glucose metabolism, and insulin levels significantly in T2DM mice. That means Hao9 contributes to improving T2DM symptoms with its potential beneficial effects. Therefore, Hao9 is a promising dietary supplement for the treatment of T2DM.

Severe hypoglycemia in patients with liver cirrhosis and type 2 diabetes.

Advanced liver disease with massive liver damage may affect the metabolism of hypoglycemic agents and increase the risk of hypoglycemia. We conduct this research to compare the risk of severe hypoglycemia between patients with type 2 diabetes, with and without compensated liver cirrhosis. From Taiwans National Health Insurance Research Database, we identified persons with type 2 diabetes with cirrhosis ( The mean follow-up period of this study was 3.7 years. The incidence rates of death during follow-up were 26.54 and 2.75 per 1,000 patient-years aHR 7.63 (6.70-8.70) for patients with cirrhosis and without cirrhosis, respectively. The incidence rates of severe hypoglycemia during follow-up were 0.53 and 0.14 per 1,000 patient-years aHR 2.74 (1.52-4.92) for patients with and without cirrhosis, respectively. The subgroup analysis of hypoglycemia risks in patients with and without cirrhosis disclosed no significant interaction for variables such as age, sex, chronic kidney disease, sulfonylurea use, number of oral antidiabetic drugs, insulin, b-blocker, and fibrate. This cohort study demonstrated that patients with type 2 diabetes and compensated cirrhosis showed a higher risk of mortality and severe hypoglycemia than those without liver cirrhosis.

Monocyte subtype expression patterns in septic patients with diabetes are distinct from patterns observed in obese patients.

Sepsis causes a high rate of mortality and long-term morbidity, associated with an imbalance of innate immunity against infections and inflammation. Obesity and diabetes increase the risk for disease severity. Monocyte dysfunction plays a major role and justify further investigations. To investigate the distribution and inflammatory phenotypes in circulating monocyte subsets in patients manifesting with sepsis including septic shock with and without obesity and diabetes. A total of 235 blood samples were tested from critically ill adult patients registered at the intensive care unit (ICU). The cohorts were divided into non-diabetic groups with or without obesity and diabetic groups with or without obesity, suffering from sepsis or septic shock. We determined frequencies of total monocytes and of monocyte subsets in the circulation and density expression levels of functional markers, including CD14, CD16, HLA-DR, CD33, CD163, CD206, and arginase-1 by flow cytometric analysis. When progressing to septic shock in non-diabetic and diabetic patients, the percentages of total monocytes among the leukocyte population and of CD33 and CD14 monocytes among the monocyte population were consistently down-regulated compared to non-sepsis in non-diabetic and diabetic patients, respectively. Non-diabetic sepsis patients further presented with decreased CD33 and up-regulated CD163 expression density, which was absent in diabetic patients. We subsequently addressed obesity-related changes of monocytes in non-diabetic and diabetic septic patients. Obese septic patients with diabetes were unique in displaying increased monocytic CD16 and CD163 expression. However, obese septic patients without diabetes solely presented with lower amounts of non-classical monocytes. Body mass index (BMI) dependent changes were restricted to diabetic septic patients, with a significantly higher diminution of the classical monocyte subset and concomitantly increased CD16 expression densities. Distribution and phenotypes of monocyte subsets were differentially modulated in critically ill patients with and without metabolic disease when progressing to sepsis or septic shock. Only diabetic septic patients displayed decline of classical monocytes and increase of CD16 expression densities. Therefore, diabetes but not obesity appears to promote the inflammatory phenotype of circulating monocytes in critically ill patients.

Role of natural products and intestinal flora on type 2 diabetes mellitus treatment.

Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern societys food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system

Screening and interventions to prevent nonalcoholic fatty liver diseasenonalcoholic steatohepatitis-associated hepatocellular carcinoma.

Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosiscirrhosis, several other risk factors for HCC have been identified (

Evaluation of histopathological changes and exosomal biogenesis in pulmonary tissue of diabetic rats.

Diabetes mellitus is one of the leading causes of death globally. The development of cellular injuries and impaired energy metabolism are involved in the pathogenesis of diabetes mellitus, leading to severe diabetic complications in different tissues such as the pulmonary tissue. Autophagy is a double-edged sword mechanism required for maintaining cell survival and homeostasis. Any abnormalities in autophagic response can lead to the progression of several diseases. Here, we aimed to assess the effect of diabetic conditions on the autophagic response and exosome secretion in a rat model of type 2 diabetes mellitus. The experimental diabetic group received 45.00 mg kg

Corrigendum Systematic review and meta-analysis of

This corrects the article DOI 10.3389fphar.2022.956313..

Bibliometric and visualized analysis of sodium-Glucose cotransporter 2 inhibitors.

Bear bile powder ameliorates type 2 diabetes

The effect of low volume high-intensity interval training on metabolic and cardiorespiratory outcomes in patients with type 2 diabetes mellitus A systematic review and meta-analysis.

The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effect of low volume high-intensity interval training (LVHIIT) on the metabolic and cardiorespiratory outcomes in patients with type 2 diabetes mellitus (T2DM). Relevant articles were sourced from PubMed, EBSCO, Web of Science, Embase, and the Cochrane Library from inception to October 2022. The study search strategy and all other processes were implemented in accordance with the PRISMA statement. Five randomized controlled trials that satisfied the inclusion criteria were included in this meta-analysis. The LVHIIT group had significantly lower fasting blood glucose levels (RR -1.21 95% CI -2.02- -0.40, p 0.0032) and HbA1c levels (RR -0.65 95% CI -1.06- -0.23, p 0.002) and higher levels of insulin resistance indicator HOMA-IR (RR -1.34 95% CI -2.59- -0.10, p 0.03) than the control group. Moreover, our results show that LVHIIT can reduce body mass (RR -0.94, 95% CI -1.37- -0.51, p<0.0001) and body mass index (RR -0.31, 95% CI -0.47- -0.16, p<0.0001). LVHIIT had a better therapeutic effect on blood lipid metabolism, such as total cholesterol, high-density lipoprotein, low-density lipoprotein and triglycerides. However, the change in fasting insulin levels was not statistically significant (RR -1.43 95% CI -3.46- 0.60, p 0.17). Furthermore, LVHIIT reduced the systolic blood pressure (RR -4.01, 95% CI -4.82 - -3.21, p<0.0001) and improved peak oxygen uptake (VO After a certain period of LVHIIT, glycaemic control, insulin resistance, body weight, lipid profile and cardiorespiratory outcomes were significantly improved in T2DM patients.

Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry.

Diabetic nephropathy (DN) is the most prominent cause of chronic kidney disease and end-stage renal failure. However, the pathophysiology of DN, especially the risk factors for early onset remains elusive. Increasing evidence has revealed the role of the innate immune system in developing DN, but relatively little is known about early immunological change that proceeds from overt DN. Herein, this work aims to investigate the immune-driven pathogenesis of DN using mass cytometry (CyTOF). The peripheral blood mononuclear lymphocytes (PBMC) from 6 patients with early-stage nephropathy and 7 type II diabetes patients without nephropathy were employed in the CyTOF test. A panel that contains 38 lineage markers was designed to monitor immune protein levels in PBMC. The unsupervised clustering analysis was performed to profile the proportion of individual cells. t-Distributed Stochastic Neighbor Embedding (t-SNE) was used to visualize the differences in DN patients immune phenotypes. Comprehensive immune profiling revealed substantial immune system alterations in the early onset of DN, including the significant decline of B cells and the marked increase of monocytes. The level of CXCR3 was dramatically reduced in the different immune cellular subsets. The CyTOF data classified the fine-grained differential immune cell subsets in the early stage of DN. Innovatively, we identified several significant changed T cells, B cell, and monocyte subgroups in the early-stage DN associated with several potential biomarkers for developing DN, such as CTLA-4, CXCR3, PD-1, CD39, CCR4, and HLA-DR. Correlation analysis further demonstrated the robust relationship between above immune cell biomarkers and clinical parameters in the DN patients. Therefore, we provided a convincible view of understanding the immune-driven early pathogenesis of DN. Our findings exhibited that patients with DN are more susceptible to immune system disorders. The classification of fine-grained immune cell subsets in this present research might provide novel targets for the immunotherapy of DN.

The relationship between glucose and the liver-alpha cell axis - A systematic review.

Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects.

Methanol extract of

Type 2 diabetes mellitus (T2DM) poses a significant risk to human health. Previous research demonstrated that

Adiponectin, IGFBP-1 and -2 are independent predictors in forecasting prediabetes and type 2 diabetes.

Adiponectin and insulin-like growth factor (IGF) binding proteins IGFBP-1 and IGFBP-2 are biomarkers of insulin sensitivity. IGFBP-1 reflects insulin sensitivity in the liver, adiponectin in adipose tissue and IGFBP-2 in both tissues. Here, we study the power of the biomarkers adiponectin, IGFBP-1, IGFBP-2, and also included IGF-I and IGF-II, in predicting prediabetes and type 2 diabetes (T2D) in men and women with normal oral glucose tolerance (NGT). Subjects with NGT (35-56 years) recruited during 1992-1998 were re-investigated 8-10 years later. In a nested case control study, subjects progressing to prediabetes (133 women, 164 men) or to T2D (55 women, 98 men) were compared with age and sex matched NGT controls (200 women and 277 men). The evaluation included questionnaires, health status, anthropometry, biochemistry and oral glucose tolerance test. After adjustment, the lowest quartile of adiponectin, IGFBP-1 and IGFBP-2 associated independently with future abnormal glucose tolerance (AGT) in both genders in multivariate analyses. High IGFs predicted weakly AGT in women. In women, low IGFBP-2 was the strongest predictor for prediabetes (OR7.5), and low adiponectin for T2D (OR29.4). In men, low IGFBP-1 was the strongest predictor for both prediabetes (OR13.4) and T2D (OR14.9). When adiponectin, IGFBP-1 and IGFBP-2 were combined, the ROC-AUC reached 0.87 for women and 0.79 for men, higher than for BMI alone. Differences were observed comparing adipocyte- and hepatocyte-derived biomarkers in forecasting AGT in NGT subjects. In women the strongest predictor for T2D was adiponectin and in men IGFBP-1, and for prediabetes IGFBP-2 in women and IGFBP-1 in men.

Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects.

Adipose tissue malfunction leads to altered adipokine secretion which might consequently contribute to an array of metabolic diseases spectrum including obesity, diabetes mellitus, and cardiovascular disorders. Asprosin is a novel diabetogenic adipokine classified as a caudamin hormone protein. This adipokine is released from white adipose tissue during fasting and elicits glucogenic and orexigenic effects. Although white adipose tissue is the dominant source for this multitask adipokine, other tissues also may produce asprosin such as salivary glands, pancreatic B-cells, and cartilage. Significantly, plasma asprosin levels link to glucose metabolism, lipid profile, insulin resistance (IR), and β-cell function. Indeed, asprosin exhibits a potent role in the metabolic process, induces hepatic glucose production, and influences appetite behavior. Clinical and preclinical research showed dysregulated levels of circulating asprosin in several metabolic diseases including obesity, type 2 diabetes mellitus (T2DM), polycystic ovarian syndrome (PCOS), non-alcoholic fatty liver (NAFLD), and several types of cancer. This review provides a comprehensive overview of the asprosin role in the etiology and pathophysiological manifestations of these conditions. Asprosin could be a promising candidate for both novel pharmacological treatment strategies and diagnostic tools, although developing a better understanding of its function and signaling pathways is still needed.

Metabolic remodeling of glycerophospholipids acts as a signature of dulaglutide and liraglutide treatment in recent-onset type 2 diabetes mellitus.

As metabolic remodeling is a pathological characteristic in type 2 diabetes (T2D), we investigate the roles of newly developed long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as dulaglutide and liraglutide on metabolic remodeling in patients with recent-onset T2D. We recruited 52 cases of T2D and 28 control cases in this study. In the patient with T2D, 39 cases received treatment with dulaglutide and 13 cases received treatment with liraglutide. Using untargeted metabolomics analysis with broad-spectrum LC-MS, we tracked serum metabolic changes of the patients from the beginning to the end of follow-up (12 We identified 198 metabolites that were differentially expressed in the patients with T2D, compared to the control group, in which 23 metabolites were significantly associated with fasting plasma glucose. Compared to pre-treatment, a total of 46 and 45 differentially regulated metabolites were identified after treatments with dulaglutide and liraglutide, respectively, in which the most differentially regulated metabolites belong to glycerophospholipids. Furthermore, a longitudinal integration analysis concurrent with diabetes case-control status revealed that metabolic pathways, such as the insulin resistance pathway and type 2 diabetes mellitus, were enriched after dulaglutide and liraglutide treatments. Proteins such as GLP-1R, GNAS, and GCG were speculated as potential targets of dulaglutide and liraglutide. In total, a metabolic change in lipids existed in the early stage of T2D was ameliorated after the treatments of GLP-1RAs. In addition to similar effects on improving glycemic control, remodeling of glycerophospholipid metabolism was identified as a signature of dulaglutide and liraglutide treatments.

Adolopment of adult diabetes mellitus management guidelines for a Pakistani context Methodology and challenges.

Pakistan has the highest national prevalence of type 2 diabetes mellitus (T2DM) in the world. Most high-quality T2DM clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local T2DM CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of adult DM in Pakistan. We employed the GRADE-ADOLOPMENT approach utilizing the T2DM CPG of the American Diabetes Association (ADA) Standards of Medical Care in Diabetes - 2021 as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. The source document contained 243 recommendations, 219 of which were adopted without change, 5 with minor changes, and 18 of which were excluded in the newly created Pakistani guidelines. One recommendation was adapted the recommended age to begin screening all individuals for T2DMpre-diabetes was lowered from 45 to 30 years, due to the higher prevalence of T2DM in younger Pakistanis. Exclusion of recommendations were primarily due to differences in the healthcare systems of Pakistan and the US, or the unavailability of certain drugs in Pakistan. A CPG for the management of T2DM in Pakistan was created. Our newly developed guideline recommends earlier screening for T2DM in Pakistan, primarily due to the higher prevalence of T2DM amongst younger individuals in Pakistan. Moreover, the systematic methodology used is a significant improvement on pre-existing T2DM CPGs in Pakistan. Once these evidence based CGPs are officially published, their nationwide uptake should be top priority. Our findings also highlight the need for rigorous expanded research exploring the effectiveness of earlier screening for T2DM in Pakistan.

Association of bone mineral density with prediabetes risk among African-American and European-American adult offspring of parents with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with alterations in bone mineral density (BMD), but association between prediabetes and BMD is unclear. We analyzed BMD among the initially normoglycemic participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study in relation to incident prediabetes during 5 years of follow-up. A total of 343 participants (193 Black, 150 White) underwent DEXA during Year 1 of POP-ABC and were followed quarterly for 5 years. The mean age was 44.2 ± 10.6 years BMI was 30.2 ± 7.23 kgm Among initially normoglycemic individuals, higher baseline BMD was associated with higher risk of incident prediabetes during 5 years of follow-up.

Tear inflammation related indexes after cataract surgery in elderly patients with type 2 diabetes mellitus.

Quantitative studies on the changes in inflammation-related content in tears, especially the effect of diabetes, are lacking. In this study, we measured the preoperative and postoperative tear inflammatory mediator levels in cataract patients, focusing on the expression of inflammatory factors in postoperative cataracts in the diabetic, and investigated the effect of drugs on the control of postoperative inflammation. To study the expression of inflammatory factors in elderly people with type 2 diabetes after cataract surgery. Patients with a mean age of 70.3 ± 6.3 years were divided into group A (composed of elderly patients with cataracts and type 2 diabetes, The postoperative expression levels of MMP-2, MMP-9, TIMP-2, IL-6, and IL-20 in group A were significantly higher than those in group B, whereas the concentration of TIMP-1 in group A remained lower than that in group B. The levels of MMP-2 and IL-6 in both groups continuously increased until the peak in the first postoperative week, and then gradually decreased over the next three weeks. Ultimately, MMP-2 declined to a lower level than that preoperatively at week 4, but IL-6 decreased to the same level as that preoperatively. The level of MMP-9 peaked in the first two weeks postoperative and then returned to the same level as 1-day post-operation. The concentration of TIMP-1 post-operation remained constant at a lower level than before surgery, and TIMP-2 Levels remained stable in both groups. IL-20 content started to increase in the third week after surgery. Inflammatory factor levels in tears fluctuated before and post-operation, which indicated more severe postoperative inflammation in the first two weeks.

The assessment of prophylactic and therapeutic methods for nail infections in patients with diabetes.

Diabetes mellitus is a metabolic disease widespread around the world. It may lead to organ dysfunction, immunodeficiency, vascular complications, and peripheral neuropathy. These factors contribute to susceptibility to fungal and bacterial infections of the nails, which could have serious consequences. To evaluate the knowledge about infection prophylaxis, prevalence of pathogens and a change in quality of life among different groups of diabetic patients. The study was performed using the DLQI questionnaire, interview, physical examination, mycological tests, and a survey containing multiple choice questions. The sample consisted of 120 patients. We revealed the presence of the infection in almost all of the patients, both with type 1 and type 2 diabetes. A great number of the participants lacked a credible source of information on their disease and consequently had little understanding of possible complications and prophylaxis of the nail infections. An overwhelming majority of the patients experienced pronounced discomfort of the skin and nails and felt extremely embarrassed with their nail appearance. Further research needs to be conducted to determine the efficacy of different methods of preventing nail infections in diabetic patients. Physicians, aside from implementing appropriate treatment, need to ensure that high-risk patients receive sufficient education on the prophylaxis of nail infections and on proper foot care.

Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk A two-sample Mendelian randomization study.

Association between chronic kidney disease, obesity, cardiometabolic risk factors, and severe COVID-19 outcomes.

Chronic kidney disease (CKD) is a risk factor for acquiring severe Coronavirus disease 2019 (COVID-19) but underlying mechanisms are unknown. We aimed to study the risk associated with CKD for severe COVID-19-outcomes in relation to BMI and diabetes, since they are common risk factors both for CKD and severe COVID-19. This nationwide case-control study with data from mandatory national registries included 4684 patients admitted to the intensive care units (ICUs) requiring mechanical ventilation (cases) and 46840 population-based controls matched by age, sex and district of residency. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between severe COVID -19 and exposures with adjustment for confounders, in subgroups by BMI, and matched by type 2 diabetes. The median age was 64 years and 27.7% were female. CKD was observed in 5.4% of the cases and 1.5% of the controls whereas 1.9% and 0.3% had end-stage CKD, respectively. CKD was associated with severe COVID-19 (OR 2.20 95% CI, 1.85-2.62), continuous renal replacement therapy at ICU (OR 7.36 95% CI 5.39-10.05), and death any time after ICU admission (OR 2.51 95% CI 1.96-3.22). The risk associated with CKD for severe COVID-19 did not differ significantly by weight but was higher in non-diabetics (OR, 2.76 95% CI 2.15-3.55) than in diabetics (OR, 1.88 95% CI 1.37-2.59). CKD, especially end-stage CKD, is an important risk factor for severe COVID-19 and death after ICU-admission also in patients with normal BMI and without type 2 diabetes.

The Correlation between Type 2 Diabetes and Fat Fraction in Liver and Pancreas A Study using MR Dixon Technique.

The increased obesity results in ectopic fat deposits in liver and pancreas, which will affect insulin resistance and elevated plasma glucose with type 2 diabetes. To assess the relationship between obesity and ectopic fat deposits and diabetes, this study used the MR Dixon method for the quantification of liver and pancreas fat fraction (FF) in type 2 diabetes mellitus (T2DM) patients and healthy controls. The FF of whole liver (FFWL) and pancreas (FFWP), the maximum diameters of the pancreas, the abdominal subcutaneous adipose area (SAT), the visceral adipose tissue area (VAT), and the total abdominal adipose tissue area (TAT) were measured for 157 subjects using the MR Dixon data. Four groups were established on the basis of BMI value. For statistics, intra- and intergroup comparisons were made by employing independent sample FFWL, FFWP, and VAT varied significantly between T2DM (BMI < 25) and control group (BMI < 25), T2DM (BMI ≥ 25) and control group (BMI ≥ 25), T2DM (BMI < 25) and T2DM (BMI ≥ 25) (all The tissue FF, which has a close relationship with T2DM, can be assessed by the MR Dixon technique. T2DM patients should pay attention to tissue fat content regardless of BMI values.

Effect of

A study to evaluate the knowledge, vaccination status and acceptance of adult vaccinations against respiratory infections in patients with type 2 diabetes in South India.

Respiratory infections like influenza and pneumococcus increase mortality, morbidity, hospitalisation risks and healthcare costs in people with type 2 diabetes which can be prevented by vaccinations. However, there is not much data regarding how many people with type 2 diabetes in India receive pneumococcal and influenza vaccinations. This is a cross-sectional study conducted between March 2022 to May 2022 at a tertiary care centre in South India. Patients were interviewed through face to face questionnaire regarding awareness, knowledge of influenza and pneumococcal infections, availability and need of vaccines, vaccination status and the possible reasons for not receiving vaccines. A total of 388 patients were recruited in the study. Knowledge about influenza and pneumococcal infections were present only in 4.8% and 4.1% respectively. And 98.7% of patients had no awareness about the availability and need for vaccines. Only 0.5% and 0.7% of patients received influenza and pneumococcal vaccinations respectively. After counselling and spreading awareness, 76.2% of patients said that they would receive vaccination in the next visit. Also, 23.19% of the patients refused to take any vaccinations even after counselling. And 23.7% of patients feared complications after vaccinations. Pneumococcal and Influenza vaccination uptake rates are extremely low in people with type 2 diabetes in India. Urgent measures are required to increase the awareness in patients and healthcare workers about the availability, need for vaccinations and effectiveness of vaccines which would lead to improvement in vaccination rates.

Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing.

Type 2 diabetes mellitus (T2DM) increases the risk of many lethal and debilitating conditions. Among them, foot ulceration due to neuropathy, vascular disease, or trauma affects the quality of life of millions in the United States and around the world. Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase. Despite advanced treatment, diabetic foot ulcers (DFUs) are associated with a risk of amputation. Thus, there is a need for novel therapies to address chronic inflammation, decreased angiogenesis, and impaired granulation tissue formation contributing to the non-healing of DFUs. Studies have shown promising results with resolvins (Rv) and anti-inflammatory therapies that resolve inflammation and enhance tissue healing. But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency, tissue targetability, and immunogenicity. This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs. The articles discussing the T2DM disease state, current research on Rv for treating inflammation, the role of Rv in enhancing wound healing, and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy. The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with anti-inflammatory agents as promising therapeutic agents in ulcer healing.

First study on the outcomes of biliopancreatic diversion with duodenal switch in Chinese patients with obesity.

Biliopancreatic diversion with duodenal switch (BPD-DS) is a bariatric procedure used in the treatment of obesity and related metabolic disorders. However, to date, the data on BPD-DS among Chinese patients with obesity is completely lacking. This is the first study to evaluate the safety and efficacy of BPD-DS in the treatment of Chinese patients with obesity. Data from 12 patients undergoing BPD-DS between September 2019 and March 2020 were analyzed retrospectively to evaluate complications, weight loss, comorbidity resolution, and nutritional status. All patients completed the 1-year follow-up. There was no conversion to laparotomy or death. Mean operative time was 257.08 ± 29.27 min. The median length of stay was 7 days (ranging from 4-38 days). Complications occurred in three patients. The 1-year body mass index was 25.13 ± 4.71 kgm BPD-DS had excellent weight loss and resolution of comorbidities among Chinese patients with obesity. However, high rates of nutritional deficiencies and complications were found after BPD-DS, especially for vitamin A and vitamin E.

Evolution of care in cirrhosis Preventing hepatic decompensation through pharmacotherapy.

Cirrhosis is a leading cause of morbidity and mortality, impacting more than 120 million people worldwide. Although geographic differences exist, etiologic factors such as alcohol use disorder, chronic viral hepatitis infections, and non-alcoholic fatty liver disease are prevalent in nearly every region. Historically, significant effort has been devoted to modifying these risks to prevent disease progression. Nevertheless, more than 11% of patients with compensated cirrhosis experience hepatic decompensation each year. This transition signifies the most important prognostic factor in the natural history of the disease, corresponding to a decline in median survival to below 2 years. Over the past decade, the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized, and non-selective beta-blockers have emerged as the most effective option to date. However, a critical therapeutic gap still exists, and additional therapies have been proposed, including statins, rifaximin, and sodium-glucose cotransporter-2 inhibitors. Based on the results of innovative retrospective analyses and small-scale prospective trials, these pharmacotherapies represent promising options, but further studies, including randomized controlled trials, are necessary before they can be incorporated into clinical use. This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.

Management of metabolic-associated fatty liver disease The diabetology perspective.

The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease (MAFLD) and type 2 diabetes mellitus (T2DM). Because of the similarity in pathobiology shared between T2DM and MAFLD, both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases. In fact, awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists. Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and, when necessary, liaising with dieticians and surgeons. This comprehensive review is to compile the current evidence from a diabetologists perspective on MAFLD and T2DM and to suggest optimal management strategies.

Type 4 renal tubular acidosis and uric acid nephrolithiasis two faces of the same coin

The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine. Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes andor chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA. Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation.

Identifying diabetogenic drugs using real world health care databases A Danish and Australian symmetry analysis.

Drug-induced diabetes is underreported in conventional drug safety monitoring and may contribute to the increasing incidence of type 2 diabetes. Therefore, we used routinely collected prescription data to screen all commonly used drugs for diabetogenic effects. Leveraging the Danish nationwide health registries, we used a case-only symmetry analysis design to evaluate all possible associations between drug initiation and subsequent diabetes. The study was conducted among individuals aged ≥40 years with a first-ever prescription for any antidiabetic drug 1996-2018 (n 348 996). Sequence ratios (SRs) and 95% confidence intervals (CIs) were obtained for all possible drug class-diabetes combinations. A lower bound of the 95% CI >1.00 was considered a signal. Signals generated in Denmark were replicated using the Services Australia, Pharmaceutical Benefits Scheme 10% data extract. Overall, 386 drug classes were investigated, of which 70 generated a signal. In total, 43 were classified as previously known based on the SIDER database or a literature review, for example, glucocorticoids (SR 1.67, 95% CI 1.62-1.72) and β-blockers (SR 1.20, 95% CI 1.16-1.23). Of 27 new signals, three drug classes yielded a signal in both the Danish and Australian data source digitalis glycosides (SR 2.15, 95% CI 2.04-2.27, and SR 1.76, 95% CI 1.50-2.08), macrolides (SR 1.20, 95% CI 1.16-1.24, and SR 1.11, 95% CI 1.06-1.16) and inhaled β2-agonists combined with glucocorticoids (SR 1.35, 95% CI 1.28-1.42, and SR 1.14, 95% CI 1.06-1.22). We identified 70 drug-diabetes associations, of which 27 were classified as hitherto unknown. Further studies evaluating the hypotheses generated by this work are needed, particularly for the signal for digitalis glycosides.

Association between medication regimen complexity and glycemic control among patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) and comorbid conditions require patients to take complex medication regimens. Greater regimen complexity has been associated with poorer T2DM management however, the relationship between overall regimen complexity and glycemic control is unclear. Our objectives were (1) to examine associations between regimen complexity (with the Medication Regimen Complexity Index MRCI) and glycemic control (A1C), and (2) to compare overall MRCI with other measures of regimen complexity (overall and diabetes-specific medication count) and diabetes-specific MRCI. This was a secondary data analysis of cross-sectional data from a parent trial. Participants were patients with T2DM taking at least 3 chronic medications followed in safety net clinics in the Chicago area. The MRCI measures complexity based on dosing frequency, route of administration, and special instructions for prescribed medications. MRCI scores were created for overall regimens and diabetes-specific medications. Sociodemographics and outpatient visit utilization were included in models as covariates. Linear regression was used to examine the associations between variables of interest and hemoglobin A1C. Participants (N 432) had a mean age of 56.9 years, most were female (66.0%), and Hispanic or Latino (73.3%). Regimen complexity was high based on overall medications (mean 6.6 medications, SD 3.09) and MRCI (mean 21.4, SD 11.3). Higher diabetes-specific MRCI was associated with higher A1C in bivariate and multivariable models. In multivariable models, overall MRCI greater than 14, fewer outpatient health care visits, male gender, and absence of health insurance were independently associated with higher A1C. The variance in A1C explained by MRCI was higher compared to medication count for overall and diabetes-specific regimen complexity. More complex regimens are associated with worse A1C and measuring complexity with MRCI may have advantages. Deprescribing, increasing insurance coverage, and promoting engagement in health care may improve A1C among underserved populations with complex regimens.

Mumefural prevents insulin resistance and amyloid-beta accumulation in the brain by improving lowered interstitial fluid pH in type 2 diabetes mellitus.

The present study tried to clarify if mumefural would prevent hyperglycemia, one of the typical symptoms of type 2 diabetes mellitus (T2DM), since mumefural is an extract from Japanese apricots preventing hyperglycemia. To clarify if mumefural would prevent T2DM pathogenesis, we used Otsuka Long-Evans Tokushima fatty (OLETF) rats, T2DM model. Mumefural diminished hyperglycemia, HOMA-IR and plasma triglyceride concentration in OLETF rats under fasting conditions. In addition, mumefural elevated protein expression of sodium-coupled monocarboxylate transporter 1 (SMCT1) in the distal colon participating in absorption of weak organic acids, which behave as bases but not acids after absorption into the body. Mumefural also increased the interstitial fluid pH around the brain hippocampus lowered in OLETF rats compared with non-T2DM LETO rats used as control for OLETF rats. Amyloid-beta accumulation in the brain decreased in accordance with the pH elevation. On the one hand, mumefural didnt affect plasma concentrations of glucagon, GLP-1, GIP or PYY under fasting conditions. Taken together, these observations indicate that 1) mumefural would be a useful functional food improving hyperglycemia, insulin resistance and the lowered interstitial fluid pH in T2DM 2) the interstitial fluid pH would be one of key factors influencing the accumulation of amyloid-beta.

Economic burden of low cardiorespiratory fitness in Canada.

The objective of this study was to estimate health care and health-related productivity costs associated with low cardiorespiratory fitness (CRF) in Canadian adults. We also estimated costs that would be avoided by a 10 percentage point prevalence reduction in low CRF. A prevalence-based approach was used to estimate the economic costs associated with low CRF. Three pieces of information were used (1) the pooled relative risk estimates of adverse health outcomes consistently associated with low CRF obtained from meta-analyses of prospective cohort studies (2) the prevalence of low CRF in Canadian men and women obtained from a nationally representative sample and (3) the direct (health care) and indirect (lost productivity due to premature mortality) costs of the adverse health outcomes based on the Economic Burden of Illness in Canada data. We estimated the total annual economic burden of low CRF in Canadian adults at CAD$3.6 billion, representing 2.7% of the overall Canadian burden of illness costs in 2021. The three most expensive chronic diseases attributable to low CRF were type 2 diabetes (CAD$1.3 billion), heart disease (CAD$701 million), and depressionanxiety (CAD$565 million). Prescription drug expenditures and hospital care expenditures were the main contributors to the total economic burden. An absolute 10% reduction in the prevalence of low CRF (from 45.5% to 35.5%) would save an estimated CAD$644 million per year in costs. In conclusion, low CRF is an important contributor to the economic burden of illness in Canada. Evidence-based and cost-effective strategies that aim to increase CRF at the population level may help alleviate health care costs and improve health.

Intestinal microbiome diversity of diabetic and non-diabetic kidney disease Current status and future perspective.

A significant portion of the health burden of diabetic kidney disease (DKD) is caused by both type 1 and type 2 diabetes which leads to morbidity and mortality globally. It is one of the most common diabetic complications characterized by loss of renal function with high prevalence, often leading to acute kidney disease (AKD). Inflammation triggered by gut microbiota is commonly associated with the development of DKD. Interactions between the gut microbiota and the host are correlated in maintaining metabolic and inflammatory homeostasis. However, the fundamental processes through which the gut microbiota affects the onset and progression of DKD are mainly unknown. In this narrative review, we summarised the potential role of the gut microbiome, their pathogenicity between diabetic and non-diabetic kidney disease (NDKD), and their impact on host immunity. A well-established association has already been seen between gut microbiota, diabetes and kidney disease. The gut-kidney interrelationship is confirmed by mounting evidence linking gut dysbiosis to DKD, however, it is still unclear what is the real cause of gut dysbiosis, the development of DKD, and its progression. In addition, we also try to distinguish novel biomarkers for early detection of DKD and the possible therapies that can be used to regulate the gut microbiota and improve the host immune response. This early detection and new therapies will help clinicians for better management of the disease and help improve patient outcomes.

Stories for change protocol A randomized controlled trial of a digital storytelling intervention for HispanicLatino individuals with type 2 diabetes.

HispanicLatino adults are disproportionately impacted by type 2 diabetes mellitus (T2D). The Stories for Change (S4C) Diabetes digital storytelling intervention promotes T2D self-management among HispanicLatino people. We describe the S4C protocol and participant baseline characteristics. Study eligibility criteria Hispanic or Latino, age 18-70 years, ≥1 office visit within a year at a participating clinic, T2D diagnosis for ≥6 months, HbA1c ≥ 8%, and intention to continue care at the recruitment clinic. We used a two-group, parallel randomized controlled trial design and an intervention derived through a community-based participatory research approach. All participants received usual diabetes care and two cards describing how to engage healthcare teams and access diabetes-related resources. At baseline, the intervention group additionally viewed the 12-min, intervention video (four stories about diabetes self-management). To encourage subsequent video viewing, participants received five monthly text messages. The messages prompted them to self-rate their motivation and self-efficacy for T2D management. The control group received no additional intervention. Bilingual (EnglishSpanish) staff collected data at baseline, six weeks, three months, and six months including biometric measurements and a survey on diabetes self-management outcomes, theory-based measures, and the number of video views. We reviewed the number of diabetes-related appointments attended using electronic medical record data. Participants (n 451 70% women, mean age 53 years) had an average HbA1C ≥9%. Intervention participants reported identifying with the storytellers and engaging with the stories. We present a digital storytelling intervention protocol that provides a template for future health promotion interventions prioritizing health disparity populations. govNCT03766438.

Adherence to the EAT-Lancet diet, genetic susceptibility, and risk of type 2 diabetes in Swedish adults.

In 2019, the EAT-Lancet Commission proposed a mainly plant-based diet that nurtures human health and supports environmental sustainability. However, its association with type 2 diabetes (T2D) has not been widely studied, and it remains unclear whether genetic susceptibility for T2D can modify this association. The aim was therefore to investigate the association between the EAT-Lancet diet and risk of T2D and assess whether the association differs by the genetic predisposition to T2D. A total of 24,494 participants from the Malmö Diet and Cancer study were analyzed. Dietary intake was assessed using a modified diet history methodology, and an EAT-Lancet diet index (range from 0 to 42 points) was constructed based on the EAT-Lancet reference diet. National and local registers were used to identify T2D cases during follow-up. Cox proportional hazards regression model was applied to estimate the association between the EAT-Lancet diet index and risk of T2D. Genetic predisposition to T2D was captured based on 116 single nucleotide polymorphisms. During a median of 24.3 years of follow-up, 4197 (17.1 %) T2D cases were documented. Compared with those with the lowest adherence to the EAT-Lancet diet (≤13 points), participants who had the highest adherence (≥23 points) showed an 18 % (95 % CI 4 %-30 %) lower risk of T2D (P for trend <0.01). There was no significant multiplicative interaction between genetic predisposition to T2D and the EAT-Lancet diet index (P 0.59). Also, no significant additive interaction between the genetic risk and the EAT-Lancet diet was seen (P 0.44). The highest risk was observed among the 22.9 % of the individuals with high genetic risk and low EAT-Lancet diet score (HR 1.79 95 % CI 1.63, 1.96). Our findings indicate that high adherence to the EAT-Lancet diet was associated with decreased risk of incident T2D among people with different genetic risks.

The Safety and Efficacy of GLP-1 Receptor Agonists in Heart Failure Patients A Systematic Review and Meta-Analysis.

Evaluation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) usage in heart failure (HF) patients with or without type 2 diabetes mellitus (T2DM) Could be proven to be a critical breakthrough in treatment options available for these patients. Our study focuses on understanding the safety and efficacy of GLP-1 RAs in this patient population by pooling the data from 9 randomized controlled trials (RCTs) comprising 871 subjects. As compared with the placebo, GLP-1 RAs did not improve major adverse cardiovascular events (MACE) which include cardiovascular (CV) mortality and heart failure (HF) hospitalizations, our primary outcome. CV mortality (RR1.03, 95% CI0.56-1.88, P0.92) and HF hospitalizations (RR1.18, 95%CI0.93-1.51, P0.18). Similarly, GLP-1 RAs did not improve our secondary findings of left ventricular ejection fraction (LVEF) and 6-minute walk test (6MWT). LVEF (RR1.96, 95%CI-0.16-4.07, P0.07) or 6 MWT (RR8.43, 95% CI-2.69-19.56, P0.14). This meta-analysis shows that GLP-1 RAs do not improve cardiovascular outcomes in HF patients with or without T2DM.

Compound Danshen Dripping Pills moderate intestinal flora and the TLR4MyD88NF-κB signaling pathway in alleviating cognitive dysfunction in type 2 diabetic KK-Ay mice.

Bidirectional communications between the gut microbiota and the brain may play a critical role in diabetes-related cognitive impairment. Compound Danshen Dripping Pills (CDDP) treatment has shown remarkable improvement in cognitive impairment in people with type 2 diabetes mellitus (T2DM) in clinical settings, but the underlying mechanisms remain unknown. An extensive detailed strategy via in vivo functional experiments, transcriptomics, metabolomics, and network pharmacology was adopted to investigate the CDDP-treatment mechanism in diabetic cognitive dysfunction. For 12 weeks, KK-Ay mice, a spontaneous T2DM model, were intragastrically administered various doses of CDDP solution or an equivalent volume of water, and the nootropic drug piracetam was orally administered as a positive control. At the 12th week, cognition was assessed using Morris water maze tests and brain magnetic resonance imaging (MRI). Furthermore, transcriptomics, metabolomics, and network pharmacology analyses were applied to reveal novel molecular mechanisms of CDDP-treatment in diabetic cognitive dysfunction of KK-Ay mice, which were then validated using quantitative real-time polymerase chain reaction and Western blot. Here we verified that CDDP can suppress inflammatory response and alleviate the cognitive dysfunction in KK-Ay mice. Also, as demonstrated by 16S rRNA sequencing and short-chain fatty acids (SCFAs) analysis, CDDP attenuated intestinal flora disorder as well as increases of metabolites including butyric acid, hexanoic acid, and isohexic acid. Given the integrated analyses of network pharmacology, transcriptomic, metabolomic data, and molecular biology, the TLR4MyD88NF-κB signaling pathway was activated in diabetes, which could be reversed by CDDP. Our findings demonstrate that CDDP restructures the gut microbiota composition and increased the intestinal SCFAs in KK-Ay mice, which might inhibit neuroinflammation, and thus improve diabetic mice cognitive disorder.

Diosgenin attenuates non-alcoholic fatty liver disease in type 2 diabetes through regulating SIRT6-related fatty acid uptake.

More than 70% of patients with type 2 diabetes (T2DM) concomitantly suffer from Non-alcoholic fatty liver disease (NAFLD), and the coexistence and interaction of them increases the intractability of NAFLD. With the protective effect against hepatic steatosis and liver fibrosis, SIRT6 is becoming a notable target of NAFLD. Diosgenin, an active monomer from Chinese herbs, has been reported to protect against NAFLD. This study aims to figure out the mechanism how diosgenin alleviate NAFLD in T2DM and the relationship with SIRT6. In vivo studies used spontaneous diabetic dbdb mice and divided them into two parts. The first part included four groups consisting of control (Con) group, model (Mod) group, low dose of diosgenin (DL) group and high dose of diosgenin (DH) group. The second part included four groups consisting of Con group, Mod group, DHOSS (OSS128167, inhibitor of SIRT6) group, MDL (MDL800, agonist of SIRT6) group. HepG2 cell line was selected in study in vitro, which was mainly composed of six groups including Con group, palmitic acid (PA) group, PADL group, PADH group, PADHOSS group, PAMDL group. OGTT, Biochemical biomarker (including TG, TC, AST, ALT), inflammatory biomarker (including IL-6 and TNF-α) were measured. HE, Oil Red O, and DHE staining were conducted. Immunohistochemistry, immunofluorescence, mRNA-seq, and qPCR were used to explore the mechanism. Results in the first part of study in vivo indicated that diosgenin protected against lipid accumulation, oxidative stress, cell injury, and light inflammatory of liver in dbdb mice and regulated the expression of SIRT6 and fatty acid transporter including CD36, FATP2, FABP1. The effect of diosgenin could be reversed in DHOSS group and the same effect was observed in MDL group in the second part of study in vivo. The same results were also noted in followed study in vitro. Diosgenin inhibited the fatty acids uptake and regulated the expression of SIRT6 and fatty acid transporter including CD36, FATP2, and FABP1 in PA-induced hepG2 cells, and which was reversed in DHOSS group and resembled in MDL group. Diosgenin could attenuate non-alcoholic fatty liver disease in type 2 diabetes through regulating SIRT6-related fatty acid uptake.

Association of peripheral neuropathy with subclinical left ventricular dysfunction in patients with type 2 diabetes.

The impacts of diabetic peripheral neuropathy (DPN) on clinical manifestations of left ventricular (LV) function in patients suffering from type 2 diabetes mellitus (T2DM) and the preserved LV ejection fraction (LVEF) lack a full evaluation. This study was carried out to investigate the correlation of peripheral neuropathy with subclinical LV systolic dysfunction, accompanied by the exploration of the relevant clinical features of peripheral neuropathy in these patients. A retrospective analysis was conducted depending on the data of 101 consecutive inpatients with T2DM and preserved LVEF (all ≥ 50 %), without coronary artery disease and other histories of heart disease. All subjects received both a nerve conduction assessment and a speckle-tracking echocardiography examination. Global longitudinal strain (GLS) was conducted to assess the subclinical LV systolic function. Forty-six (46 %) patients were diagnosed as DPN according to electrophysiological examination and clinical assessment. A significant difference was revealed in GLS between patients with and without DPN (16.5 ± 2.8 vs. 19.3 ± 3.4, p < 0.001). Multiple logistic regression analysis indicated GLS as one of the independent determinative factors for DPN (odds ratio, 0.68 P < 0.001). In addition, motor-sensory nerve conduction exhibited a significant positive correlation with GLS, which may not be revealed between the types of peripheral nerve damage. Despite the preserved LVEF, the subclinical LV myocardial dysfunction may have occurred in T2DM patients with DPN. Peripheral nerve conduction was significantly correlated with GLS. An early assessment of nerve conduction may exert a dual warning significance for the progression of subclinical LV dysfunction in asymptomatic patients with T2DM.

The association between diabetes complications and symptoms of depression and anxiety.

The bidirectional relationship between diabetes and depression results in severe disease burden. Co-occurring depression is associated with a higher rate of diabetes complications. These complications impair quality of life, however, their impact on depressive symptoms is controversial. In our cross-sectional study, we aimed to investigate whether the presence of diabetes complications is associated with depressive and anxiety symptoms among patients with type 2 diabetes in general practice. We obtained patient history, anthropometric, socioeconomic, laboratory parameters. For symptom assessment, the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAM-A) were used. We collected data between September 2018 and February 2020. We included 338 consecutive patients with type 2 diabetes. The mean age of the sample was 63.98 ± 11.51 (years ± SD), 61.2% of participants were female. We found significant univariate association between diabetes complications and older age, less physical activity, higher body mass index, insulin therapy, higher HbA1c, higher creatinine and carbamide concentrations, worse depressive and anxiety symptoms. In multivariate analysis, diabetes complications and certain socio-demographic factors (female gender, lower education, rural-dwelling) were the determinants of higher BDI and HAM-A scores. Among primary care patients with type 2 diabetes, the prevalence of depressive and anxiety symptoms was higher and more severe in patients with diabetes complications. The recommended screening for affective disorders among patients with diabetes is especially justified if complications are present. Orv Hetil. 2023 164(3) 79-87. Bevezetés A diabetes és a depresszió együttes fennállása esetén a kétirányú kapcsolatból adódóan jelentős a betegségteher. A depresszióval szövődött cukorbetegség esetén nagyobb arányban fordulnak elő komplikációk. Bár a szövődmények életminőséget rontó hatása jól ismert, depressziós tüneteket fokozó hatásuk vitatott. Célkitűzés Keresztmetszeti vizsgálatunkat háziorvosi praxisokban, 2-es típusú cukorbetegek körében végeztük, és arra kerestünk választ, hogy van-e összefüggés a diabetes szövődményei és a depressziós, illetve szorongásos tünetek fennállása között. Módszer Felvettük a szociodemográfiai, antropometriai és anamnesztikus adatokat, rögzítettük a laborparamétereket. A depressziós tünetegyüttes becslésére a 21 kérdéses Beck Depresszió Kérdőívet (BDI), a szorongás súlyosságának meghatározására a Hamilton Szorongás Skálát (HAM-A) alkalmaztuk. Az adatrögzítést 2018. szeptember és 2020. február között végeztük. Eredmények A vizsgálatban 338 beteg vett részt, az átlagéletkor 63,98 ± 11,51 év (± SD) volt, 61,2%-uk volt nő. Szignifikáns összefüggést találtunk a szövődmények jelenléte és a magasabb életkor, a kevesebb fizikai aktivitás, a magasabb testtömegindex, az inzulinterápia, az emelkedett HbA1c-érték, a rosszabb vesefunkciós paraméterek, a súlyosabb depressziós és szorongásos tünetek között. Többváltozós analízissel a BDI- és a HAM-A-pontszám független meghatározójának egyes demográfiai jellemzők mellett (női nem, alacsonyabb végzettség, fővároson kívüli lakóhely) a szövődmények fennállása bizonyult. Következtetés Vizsgálatunk alapján szövődmények jelenléte esetén gyakoribbak és súlyosabbak a depressziós és a szorongásos tünetek. A hangulatzavaroknak a cukorbetegek körében javasolt szűrése és kezelése különösen szövődmények fennállása esetén indokolt. Orv Hetil. 2023 164(3) 79–87.

Physician-led medication reviews in polypharmacy patients treated with at least 12 medications in a type 2 diabetes outpatient clinic A randomised trial.

Medication reviews can be used to promote appropriate pharmacotherapy and negate the harmful consequences of polypharmacy. This study aimed to evaluate the effect of physician-led medication reviews and increased cross-sectoral communication as a supplement to standard care in a type 2 diabetes outpatient clinic. This pragmatic randomised clinical trial enrolled patients with type 2 diabetes treated with at least 12 medications. The subjects were randomised to either standard care (standard care consultation at the outpatient clinic) or standard care plus a medication review consultation and increased cross-sectoral communication. The primary outcome was the number of medications used after six months. Health-related quality of life was quantified using the EuroQoL 5-dimension 5-level (EQ5D-5 L) questionnaire. We recruited 50 participants with a median age of 72 (IQR 67-75) years. The mean number of medications per patient changed from 17.9 to 14.3 in the intervention group and 17.6 to 17.2 in the control group (rate ratio 0.81). The reasons for discontinuations were medication no longer indicated (60%), safety issues (20%), efficacy issues (15%) or patient preferences (5%). There was a significant difference in the change in health-related quality of life (EQ5D-5 L index score) in favour of the intervention (0.111, 95% CI 0.001 to 0.221). Physician-led medication reviews and increased cross-sectoral communication in patients with type 2 diabetes treated with at least 12 medications reduced the number of medications used and improved health-related quality of life. Implementing and further investigating similar interventions as standard care seems reasonable.

Sex difference in the relationship of the Atherogenic index of plasma with coronary artery lesions in diabetes a cross-sectional study.

Coronary artery disease (CAD) tends to progress more rapidly in the type 2 diabetes mellitus (T2DM) population and may be associated with dyslipidemia. This study explored the relationship of the atherogenic index of plasma (AIP) to coronary artery lesions in the T2DM population of different sexes. The research included 737 individuals who underwent coronary angiography from 2018 to 2019. The included clinical data and coronary angiographic findings were analyzed in the study. Among the included male patients, those with coronary artery disease had a higher adjusted AIP (aAIP). In correlation analysis, the Gensini score was positively and linearly correlated with the aAIP in male T2DM patients. An aAIP cutoff value of 1.17 was determined from the receiver operating characteristic (ROC) curve of aAIP versus CAD risk in the study population. After dividing the aAIP into two groups by the cutoff value of aAIP, the group with the lower value was used as the control for logistic regression analysis. The results showed that the risk of CAD and multivessel lesions was higher when the aAIP was higher in men with T2DM, and this positive association was not affected by HbA1c, age, or the presence of glucose-lowering therapy. The ROC curve suggested that the aAIP can predict CAD risk in male T2DM patients. However, no relationship was found in the included female patients. In male T2DM patients, AIP may serve as a reliable marker for coronary artery lesions.

MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC) randomized clinical trial protocol.

Peripheral artery disease (PAD) affects over 230 million people worldwide and is due to systemic atherosclerosis with etiology linked to chronic inflammation, hypertension, and smoking status. PAD is associated with walking impairment and mobility loss as well as a high prevalence of coronary and cerebrovascular disease. Intermittent claudication (IC) is the classic presenting symptom for PAD, although many patients are asymptomatic or have atypical presentations. Few effective medical therapies are available, while surgical and exercise therapies lack durability. Metformin, the most frequently prescribed oral medication for Type 2 diabetes, has salient anti-inflammatory and promitochondrial properties. We hypothesize that metformin will improve function, retard the progression of PAD, and improve systemic inflammation and mitochondrial function in non-diabetic patients with IC. 200 non-diabetic Veterans with IC will be randomized 11 to 180-day treatment with metformin extended release (1000 mgday) or placebo to evaluate the effect of metformin on functional status, PAD progression, cardiovascular disease events, and systemic inflammation. The primary outcome is 180-day maximum walking distance on the 6-min walk test (6MWT). Secondary outcomes include additional assessments of functional status (cardiopulmonary exercise testing, grip strength, Walking Impairment Questionnaires), health related quality of life (SF-36, VascuQoL), macro- and micro-vascular assessment of lower extremity blood flow (ankle brachial indices, pulse volume recording, EndoPAT), cardiovascular events (amputations, interventions, major adverse cardiac events, all-cause mortality), and measures of systemic inflammation. All outcomes will be assessed at baseline, 90 and 180 days of study drug exposure, and 180 days following cessation of study drug. We will evaluate the primary outcome with linear mixed-effects model analysis with covariate adjustment for baseline 6MWT, age, baseline ankle brachial indices, and smoking status following an intention to treat protocol. MOBILE IC is uniquely suited to evaluate the use of metformin to improve both systematic inflammatory responses, cellular energetics, and functional outcomes in patients with PAD and IC. The prospective MOBILE IC trial was publicly registered (NCT05132439) November 24, 2021.

Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment.

The human gut microbiome has been associated with several metabolic disorders including type 2 diabetes mellitus. Understanding metabolic changes in the gut microbiome is important to elucidate the role of gut bacteria in regulating host metabolism. Here, we used available metagenomics data from a metformin study, together with genome-scale metabolic modelling of the key bacteria in individual and community-level to investigate the mechanistic role of the gut microbiome in response to metformin. Individual modelling predicted that species that are increased after metformin treatment have higher growth rates in comparison to species that are decreased after metformin treatment. Gut microbial enrichment analysis showed prior to metformin treatment pathways related to the hypoglycemic effect were enriched. Our observations highlight how the key bacterial species after metformin treatment have commensal and competing behavior, and how their cellular metabolism changes due to different nutritional environment. Integrating different diets showed there were specific microbial alterations between different diets. These results show the importance of the nutritional environment and how dietary guidelines may improve drug efficiency through the gut microbiota.

Cardiac arrhythmias and conduction abnormalities in patients with type 2 diabetes.

The association between type 2 diabetes (T2D) and the development of cardiac arrhythmias and conduction disturbances has not been extensively studied. Arrhythmia was defined as atrial fibrillation and flutter (AFAFl), ventricular tachycardia (VT) and ventricular fibrillation (VF), and conduction abnormality as sinus node disease (SND), atrioventricular (AV) block or pacemaker implantation, and intraventricular conduction blocks (IVCB). Incidence rates and Cox regression were used to compare outcomes, and to assess optimal levels for cardiometabolic risk factors and risk associated with multifactorial risk factor control (i.e., HbA1c, LDL-C, systolic blood pressure (SBP), BMI and eGFR), between patients with versus without T2D. The analyses included data from 617,000 patients with T2D and 2,303,391 matched controls. Patients with diabetes and the general population demonstrated a gradual increase in rates for cardiac conduction abnormalities and virtually all age-groups for AFAFI showed increased incidence during follow-up. For patients with versus without T2D, risks for cardiac arrhythmias were higher, including for AFAFl (HR 1.17, 95% CI 1.16-1.18), the composite of SND, AV-block or pacemaker implantation (HR 1.40, 95% CI 1.37-1.43), IVCB (HR 1.23, 95% CI 1.18-1.28) and VTVF (HR 1.08, 95% CI 1.04-1.13). For patients with T2D who had selected cardiometabolic risk factors within target ranges, compared with controls, risk of arrythmia and conduction abnormalities for T2D vs not were AFAFl (HR 1.09, 95% CI 1.05-1.14), the composite of SND, AV-block or pacemaker implantation (HR 1.06, 95% CI 0.94-1.18), IVCB (HR 0.80, 95% CI 0.60-0.98), and for VTVF (HR 0.97, 95% CI 0.80-1.17). Cox models showed a linear risk increase for SBP and BMI, while eGFR showed a U-shaped association. Individuals with T2D had a higher risk of arrhythmias and conduction abnormalities than controls, but excess risk associated with T2D was virtually not evident among patients with T2D with all risk factors within target range. BMI, SBP and eGFR displayed significant associations with outcomes among patients with T2D.

N6-methylation of RNA-bound adenosine regulator HNRNPC promotes vascular endothelial dysfunction in type 2 diabetes mellitus by activating the PSEN1-mediated Notch pathway.

The regulatory mechanism of m6A regulators in vascular endothelial function of type 2 diabetes mellitus (T2DM) remains largely unknown. We addressed this issue based on the data retrieved Gene Expression Omnibus (GEO) database and experimental validations. Expression of m6A methylation regulators was evaluated in T2DM samples of GSE76894 dataset and GSE156341 dataset. Further analysis of candidate m6A methylation regulators was conducted in the thoracic aorta of dbdb mice and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). Ectopic expression and depletion experiments were conducted to detect effects of m6A methylation regulators on vascular endothelial function in T2DM. It emerged that three m6A methylation regulators (HNRNPC, RBM15B, and ZC3H13) were highly expressed in T2DM, which were related to vascular EC function, showing diagnostic values for T2DM. HNRNPC expression in the thoracic aorta of dbdb mice was higher than that in heterozygous db mice, and HNRNPC expression in HG-induced HUVECs was upregulated when compared with normal glucose-exposed HUVECs. Furthermore, HNRNPC activated PSEN1-dependent Notch pathway to induce eNOS inactivation and NO production decrease, thereby causing vascular endothelial dysfunction in T2DM. HNRNPC impaired vascular endothelial function to enhance the development of vascular complications in T2DM through PSEN1-mediated Notch signaling pathway.

Effects of coconut oil long-term supplementation in Wistar rats during metabolic syndrome - regulation of metabolic conditions involving glucose homeostasis, inflammatory signals, and oxidative stress.

This study was designed to evaluate the long-term effects of Fructose (20%) feeding in rats, simulating metabolic syndrome (MetS), and the effects of coconut oil (C.O.) supplementation when administered in a MetS context. MetS is a cluster of systemic conditions that represent an increased chance of developing cardiovascular diseases and type 2 diabetes in the future. C.O. has been the target of media speculation, and recent studies report inconsistent results. C.O. improved glucose homeostasis and reduced fat accumulation in Fructose-fed rats while decreasing the levels of triglycerides (TGs) in the liver. C.O. supplementation also increased TGs levels and fructosamine in serum during MetS, possibly due to white adipose tissue breakdown and high fructose feeding. Pro-inflammatory cytokines IL-1β and TNF-α were also increased in rats treated with Fructose and C.O. Oxidative stress marker nitrotyrosine is increased in fructose-fed animals, and C.O. treatment did not prevent this damage. No significant changes were observed in lipoperoxidation marker 4-Hydroxynonenal however, fructose feeding increased total conjugated dienes and caused conjugated dienes to switch their conformation from cis-trans to trans-trans, which was not prevented by C.O. treatment. Potential benefits of C.O. have been reported with inconsistent results, and indeed we observed some benefits of C.O. supplementation in aiding weight loss, fat accumulation, and improving glucose homeostasis. Nonetheless, we also demonstrated that long-term C.O. supplementation could present some problematic effects with higher risk for individuals suffering MetS, including increased TGs and fructosamine levels and conformational changes in dienes.

Does panic disorder increase the risk of cardiovascular diseases in diabetics A nationwide population-based study.

Several studies have suggested a link between panic disorder (PD) and cardiovascular disease (CVD). However, the extent to which PD confers risk for CVD is still unclear, particularly in diabetics, a group showing high risk for CVD. A nationwide population-based cohort of 1,624,718 patients with type 2 diabetes were selected from the National Health Screening Program database covering the years 2009 to 2012. The subjects were divided into two groups those without panic disorder (non-PD group, n 1,618,263) and those with newly diagnosed PD (PD-group, n 6455). Follow-up of subjects for up to 10 years was conducted for evaluation of the incidences of myocardial infarction (MI), stroke, and death. After adjusting for the baseline covariates and diabetes mellitus (DM)-related variables, no difference in the future risk of MI and stroke was observed between the non-PD group and the PD group. Compared with the non-PD group, the PD group showed an increase in the future risk of death. adjusted hazard ratio (aHR) 1.120, 95 % confidence interval (CI) 1.039-1.206. In contrast to the population aged <40 and > 65 years, in the age group of 40-64 years a significantly higher risk of stroke was observed in the PD group compared with the non-PD group (aHR 1.352, 95%CI 1.136-1.610). The diagnoses were based on the diagnostic codes of the claim data. The current findings suggested that PD might not contribute to the risk of future MI and stroke in diabetics who have already been at risk of various cardiovascular complications.

Advances in buccal and oral delivery of insulin.

Diabetes mellitus is a metabolic endocrine disease characterized by chronic hyperglycemia with disturbances in metabolic processes, such as those related to carbohydrates, fat, and protein. There are two main types of this disease type 1 diabetes (T1D) and type 2 diabetes (T2D). Insulin therapy is pivotal to the management of diabetes. Over the last two decades, many routes of administration, including nasal, pulmonary, rectal, transdermal, buccal, and ocular, have been investigated. Nevertheless, subcutaneous parenteral administration is still the most common route for insulin therapy. To overcome poor bioavailability and the barriers to oral insulin absorption, novel approaches in the field of oral drug delivery and administration have been brought about by the coalescence of different branches of nanoscience and nanotechnology, such as nanomedicine, nano-biochemistry, and nano-pharmacy. Novel drug delivery systems, including nanoparticles, nano-platforms, and nanocarriers, have been suggested. The objective of this review is to provide an update on the various promising approaches that have been explored and evaluated for the safe and efficient oral and buccal administration of insulin.

Synthetic α-glucosidase inhibitors as promising anti-diabetic agents Recent developments and future challenges.

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. It is a well-recognized multifactorial health problem contributes significantly to high mortality rates by causing serious health complications mainly related to cardiovascular diseases, kidney damage and neuropathy. The inhibition of α-glucosidase (enzyme that catalyses starch hydrolysis in the intestine) is an effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes. However, the presently approved drugsinhibitors such as acarbose, miglitol and voglibose have several undesirable gastrointestinal side effects impeding their applications. Therefore, search for novel and more effective inhibitors with reduced side effects and less cost remains a fascinating area of research. In this context, a large variety of α-glucosidase inhibitors have been identified in recent years that demands attention from drug development community. This review is therefore an effort to summarize and highlight the promising α-glucosidase inhibitors especially those which are primarily based on aromatic heterocyclic scaffolds such as coumarin, imidazole, isatin, pyrimidine, quinazoline, triazine, thiazole etc, having improved safety and pharmacological profiles.

Real-world safety and effectiveness of iGlarLixi in people with type 2 diabetes who fast during Ramadan The SoliRam observational study.

To evaluate the safety and effectiveness of iGlarLixi in adults with type 2 diabetes (T2D) fasting during Ramadan. SoliRam was a multinational, prospective, single-arm, real-world observational study conducted during Ramadan 2020 and 2021 in adults with T2D treated with iGlarLixi ≥3 months at study entry. The primary endpoint was the percentage of participants experiencing ≥1 episode of severe andor symptomatic documented hypoglycemia (<70 mgdL <3.9 mmolL). Among the 409 eligible participants followed during Ramadan, 96.8% fasted for ≥25 days and 92.4% did not break fasting during Ramadan. Four participants broke their fast due to hypoglycemia. Minimal adjustments were seen in antihyperglycemic therapies from pre to during Ramadan. Documented symptomatic hypoglycemia was experienced by 1.0%, 2.3%, and 0.3% of participants, respectively, during the last month of pre-Ramadan, Ramadan, and first month post-Ramadan. Mean change in HbA iGlarLixi is an effective and well-tolerated therapy for people with T2D, including those who intend to fast during Ramadan, and is associated with a low risk of hypoglycemia benefits were observed both during and after Ramadan.

The Impact of Obesity in Saudi Arabia Healthcare Resource Use and Costs Associated with Obesity-Related Complications.

Saudi Arabia has a high prevalence of obesity, which increases the risk of individuals experiencing multiple chronic complications. Only a few publications highlight the healthcare costs of obesity-related complications (ORCs) in Saudi Arabia. A micro-costing approach was used to estimate the healthcare costs associated with 10 ORCs. Experienced clinicians in public and private practice across different geographical regions in Saudi Arabia were asked to estimate healthcare resource use associated with each ORC, and estimated unit costs were obtained from hospital administrators. Estimated overall annual costs per patient were calculated as a weighted average of separate public and private sector costs. Individuals in Saudi Arabia with any single ORC incurred overall average annual healthcare costs of 2165-7558 US dollars (USD). Heart failure, chronic kidney disease, dyslipidemia, and type 2 diabetes (T2D) were the most costly complications, mainly driven by monitoring andor pharmacological treatment costs. In contrast, asthma, hypertension, and angina were the least costly complications. Costs in private healthcare were higher than in public healthcare the largest differences (2359-2793 USD) were noted for dyslipidemia, T2D, and osteoarthritis, mainly explained by differences in pharmacological treatment costs. These data suggest that ORCs result in a considerable financial burden to the healthcare system, and highlight the substantial cost savings that could be achieved by preventing or delaying the occurrence of ORCs in Saudi Arabia.

Epidemiological, Social and Economic Burden of Severe Hypoglycaemia in Patients with Diabetes Mellitus in Portugal A Structured Literature Review.

The aim of this review was to identify and review studies reporting on the epidemiological, social and economic impact associated with severe hypoglycaemia (SH) in people with diabetes mellitus (DM) in Portugal. A structured literature search was carried out in PubMed and Embase using a predefined selection criterion. Studies published in either Portuguese or English, between January 2010 and February 2021 were deemed eligible for inclusion. Twelve studies including adults (aged ≥ 18 years) with type 1 andor type 2 diabetes mellitus (T1DMT2DM) were eligible for inclusion. Epidemiological estimates varied according to the setting and type of data source used. The proportion of patients who experienced ≥ 1 SH episode (SHE) in the previous 6-12 months varied from 3.1% in adults with T2DM to 36.8% in adults with T1DM. In adults with T2DM the prevalence in a community-based study was highest in the insulin and secretagogue combination treated group (9.1%), while in an emergency department setting prevalence was highest in the insulin-based therapy group and the oral hypoglycaemic agent without secretagogues group (32.0% and 20.0%, respectively). The prevalence of SH in other studies in patients with DM ranged from 0.1% (emergency department) to 18.1% (hospital ward). Patients treated with secretagogues had the highest rates of hospitalisations. In patients with T1DM, the annual rate of SHE was higher in those with impaired hypoglycaemia awareness than in those with intact awareness. Mean total cost (direct and indirect) per SHE ranged from €1493.00 in patients with T2DM treated in an emergency setting to €2608.51 in patients with T1DM who were hospitalised. Hypoglycaemic events, especially SHE, have a significant effect on the life of persons living with DM and their caregivers. Studies show that the prevalence of this acute complication of diabetes is not negligible. In addition to the negative impact on the quality of life, the burden of SHE in Portugal translates into a significant impact on the global health expenditure.

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Mexican women have a higher prevalence of type 2 diabetes mellitus (T2DM) and less compliance with T2DM self-care compared with Mexican men. The term This was a cross-sectional study among women with T2DM who attended primary care centers in Oaxaca, Mexico during 2019. The Summary of Diabetes Self-care Activities and the Among the 547 participants, those with higher Findings suggest that Mexican women with strong

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination.

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (

Rhanteriol, a New

Several specialized plant metabolites are reported to be enzyme inhibitors. In this investigation, the phytochemical composition and the biological activity of