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Does an increase in physiological indexes predict better cognitive performance the PhyCog randomised cross-over protocol in type 2 diabetes.

There has been a growing interest towards cognitive-training programmes to improve cognition and prevent cognitive impairment despite discrepant findings. Physical activity has been recognised in maintaining or improving cognitive ability. Based on a psychoneurophysiological approach, physiological indexes should partly determine neuronal dynamics and influence cognition as any effects of cognitive training. This studys primary aim was to examine if improved physiological indexes predict improved cognitive variables in the context of a clinical intervention programme for type 2 diabetes (T2D). PhyCog will be a 22-week randomised controlled trial comparing cognitive performance between three arms (1) physical activity (1 month), a 15-day wash-out, then cognitive training (1 month), (2) cognitive training (1 month), a 15-day wash-out and physical activity (1 month), and (3) an active breathing condition (psychoeducation and resonance frequency breathing for 1 month), then a 15-day wash-out, and combined physical activity and cognitive training (1 month), allowing to determine the most effective intervention to prevent cognitive impairment associated with T2D. All participants will be observed for 3 months following the intervention. The study will include a total of 81 patients with T2D.Cognitive performance and physiological variables will be assessed at baseline (week 0-W0), during the washout (W5, 72-96 hours after week 4), at the end of the intervention (W10), and at the end of the follow-up (W22). The main variables of interest will be executive function, memory and attention. Physiological testing will involve allostatic load such as heart rate variability, microcirculation, cortisol and dehydroepiandrosterone sulfate levels. Sociodemographic and body composition will also be a consideration. Assessors will all be blinded to outcomes. To test the primary hypothesis, the relationship between improvement in physiological variables and improvement in cognitive variables (executive, memory and attention) will be collected. This protocol was approved by the Est III French Ethics Committee (2020-A03228-31). Results will be published in peer-reviewed journals. NCT04915339.

3,4-Dihydroxyphenylacetic acid ameliorates gut barrier dysfunction via regulation of MAPK-MLCK pathway in type 2 diabetes mice.

This study aims to investigate whether 3,4-dihydroxyphenylacetic acid (DHAA) can improve gut barrier function by inhibiting the mitogen-activated protein kinase (MAPK) - myosin light-chain kinase (MLCK) signaling pathway in type 2 diabetes (T2D) mice. T2D mice were induced by a high-fat diet combined with streptozotocin. T2D mice were intragastrically administered with DHAA at 75 and 150 mg kgbody weight per day for 4 weeks. Blood glucose, insulin level, oxidative stress and inflammatory cytokines were measured. TJ (tight junction) protein and MAPK-MLCK pathway-related proteins were analyzed by western blot. DHAA alleviated hyperglycemia and decreased insulin resistance of T2D mice. It also decreased oxidative stress via increased glutathione (GSH) and total superoxide dismutase (T-SOD) activities and reduced containing malondialdehyde (MDA). DHAA exhibited a significant anti-inflammatory effect by decreasing the level of pro-inflammatory cytokines lipopolysaccharide (LPS) and interleukin (IL)-6 and increasing that of anti-inflammatory cytokine IL-10. More importantly, DHAA improved gut barrier function by enhancing tight junction protein expression and inhibiting the MAPK-MLCK signaling pathway. DHAA could reduce oxidative stress, decrease inflammatory response, and improve intestinal function in T2D mice, which may help to relieve the symptoms of T2D.

Safety outcomes of SGLT2i in the heart failure trials A systematic review and Meta-analysis.

Sodium-glucose co-transporter inhibitors (SGLT2i) are emerging as a new treatment for heart failure (HF) after demonstrating favorable clinical outcomes in several randomized controlled trials (RCTs). In this meta-analysis, we assessed the safety of SGLT2i in the trials that prespecified heart failure in their inclusion criteria. We searched the databases for RCTs comparing SGLT2i to placebo in heart failure patients. The primary outcome was the incidence of serious adverse events (SAEs). A sensitivity analysis according to the class of HF was also performed. The incidence of SAEs was significantly lower in the SGLT2i group (OR, 0.85 95% CI, 0.77-0.92 P, 0.0002) and SAEs remained significantly lower after performing the sensitivity analysis (OR, 0.82 95% CI, 0.75-0.89 P, <0.00001). Genital infections, urinary tract infections (UTIs), and hypotension were significantly higher in the SGLT2i group. SGLT2i remain a safe option for patients with HF with a lower incidence of SAEs. However, since they increase the risk of genital infection, UTIs and hypotension, the risks vs benefits in each patient should be weighed when making a prescribing decision.

MB-SupCon Microbiome-based Predictive Models via Supervised Contrastive Learning.

Human microbiome consists of trillions of microorganisms. Microbiota can modulate the host physiology through molecule and metabolite interactions. Integrating microbiome and metabolomics data have the potential to predict different diseases more accurately. Yet, most datasets only measure microbiome data but without paired metabolome data. Here, we propose a novel integrative modeling framework, Microbiome-based Supervised Contrastive Learning Framework (MB-SupCon). MB-SupCon integrates microbiome and metabolome data to generate microbiome embeddings, which can be used to improve the prediction accuracy in datasets that only measure microbiome data. As a proof of concept, we applied MB-SupCon on 720 samples with paired 16S microbiome data and metabolomics data from patients with type 2 diabetes. MB-SupCon outperformed existing prediction methods and achieved high average prediction accuracies for insulin resistance status (84.62%), sex (78.98%), and race (80.04%). Moreover, the microbiome embeddings form separable clusters for different covariate groups in the lower-dimensional space, which enhances data visualization. We also applied MB-SupCon on a large inflammatory bowel disease study and observed similar advantages. Thus, MB-SupCon could be broadly applicable to improve microbiome prediction models in multi-omics disease studies.

Inflammatory profile associated with insulin resistance in non-overweight versus overweight people living with HIV in Pune, Western India.

People living with HIV have greater diabetes (T2DM) than the general population despite lower prevalence of overweightobesity. Both insulin resistance (IR), a T2DM precursor, and HIV are independently associated with chronic inflammation. Inflammation may be a pathophysiological link explaining IR in people living with HIV who are not overweight but is not well understood. To study the association between inflammation and IR in non-overweight and overweight people living with HIV. In a cohort of adult people living with HIV with undetectable viral load in Pune, India, we measured fasting insulin, glucose, and 9 inflammatory markers. IR was defined as HOMA-IR ≥2, and non-overweight as BMI ≤23 kgm Of 288 participants, 66% (n 189) were non-overweight. Among non-overweight, prevalence of IR was 34% (n 65). Each doubling of MCP-1 and leptin was associated with IR on univariate analysis (prevalence ratio (PR) 1.29, 95%CI 1.07-1.53, p < 0.01 PR 1.13 95%CI 1.01-1.26, p 0.03). Leptin remained associated with IR after adjustment for age, MCP-1, gender, cholesterol, and waist circumference (adjusted PR 1.20 95%CI 1.06-1.36, p < 0.01). Among overweight, prevalence of IR was 69% and no markers were associated with IR. One in 3 non-overweight people living with HIV in India with controlled viremia have IR. Leptin was associated with IR among non-overweight people living with HIV and may provide insight into the pathophysiology of metabolic disease in this population.

A novel stacking ensemble for detecting three types of diabetes mellitus using a Saudi Arabian dataset Pre-diabetes, T1DM, and T2DM.

Glucose is the primary source of energy for cells, which are the building blocks of life. It is given to the body by insulin that carries out the metabolic tasks that keep people alive. Glucose level imbalance is a sign of diabetes mellitus (DM), a common type of chronic disease. It leads to long-term complications, such as blindness, kidney failure, and heart disease, having a negative impact on ones quality of life. In Saudi Arabia, a ten-fold increase in diabetic cases has been documented within the last three years. DM is broadly categorized as Type 1 Diabetes (T1DM), Type 2 Diabetes (T2DM), and Pre-diabetes. The diagnosis of the correct type is sometimes ambiguous to medical professionals causing difficulties in managing the illness progression. Intensive efforts have been made to predict T2DM. However, there is a lack of studies focusing on accurately identifying T1DM and Pre-diabetes. Therefore, this study aims to utilize Machine Learning (ML) to distinguish and predict the three types of diabetes based on a Saudi Arabian hospital dataset to control their progression. Four different experiments have been conducted to achieve the highest results, where several algorithms were used, including Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbor (K-NN), Decision Tree (DT), Bagging, and Stacking. In experiments 2, 3, and 4, the Synthetic Minority Oversampling Technique (SMOTE) was applied to balance the dataset. The empirical results demonstrated promising results of the novel Stacking model that combined Bagging K-NN, Bagging DT, and K-NN, with a K-NN meta-classifier attaining an accuracy, weighted recall, weighted precision, and cohens kappa score of 94.48%, 94.48%, 94.70%, and 0.9172, respectively. Five principal features were identified to significantly affect the model accuracy using the permutation feature importance, namely Education, AntiDiab, Insulin, Nutrition, and Sex.

Rotational thromboelastometry in patients with type 2 diabetes and mild COVID-19 pneumonia A pilot prospective study.

It was repeatedly demonstrated that patients with severe COVID-19 pneumonia, as well as patients with type 2 diabetes (T2D) have higher risk of thromboembolic complications. Rotational thromboelastometry (ROTEM®) is a viscoelastic hemostatic assay which allows complex assessment of hemostasis in whole blood. The aim of this study was to compare changes in hemostasis measured by ROTEM® in diabetic and nondiabetic patients with mild COVID-19 pneumonia. We performed a pilot, prospective, observational study and enrolled 33 consecutive patients (14 with T2D and 19 nondiabetic ones) admitted to regular ward with mild COVID-19 pneumonia. The control group consisted from 11 healthy, nondiabetic blood donors. Blood samples were tested with ROTEM® using INTEM® and EXTEM® reagents. We detected significant differences in EXTEM® clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF) comparing patients with mild COVID-19 pneumonia and healthy donors. However, there were no significant differences in EXTEM®, INTEM®, and HEPTEM® parameters (CT, CFT, and MCF) according to diabetes status. Our study demonstrated hypercoagulation in patients with mild COVID-19 pneumonia. T2D did not affected ROTEM® parameters in patients with mild COVID-19 pneumonia.

Neuropathy scale score as an independent risk factor for myocardial infarction in patients with type 2 diabetes.

To investigate whether peripheral neuropathy scale scores are associated with myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). In this cross-sectional study, 32,463 T2DM patients were enroled from 103 tertiary hospitals in 25 Chinese provinces. Based on a history of MI, participants were divided into the MI group (n 4170) and the non-MI group (n 28,293). All patients were assessed using four neuropathy scales, namely, Neurological Symptom Score (NSS), Neurological Disability Score (NDS), Toronto Clinical Scoring System (TCSS), and Michigan Neuropathy Screening Instrument (MNSI), and some of the patients underwent evaluation of nerve conduction velocity (NCV) (n 20,288). The relationship between these scores and myocardial infraction was analysed. The neuropathy scale scores in the MI group were higher than those in the non-MI group (p < 0.001). After dividing patients into four groups based on the grading criteria, our results showed that, in addition to aggravating the degree of neuropathy signs, the incidence of MI increased (p < 0.001). Logistic regression analysis results showed that neuropathy scale scores and NCV were both independent risk factors for MI (p < 0.001). Furthermore, among the scales used, MNSI presented a higher odds ratio and area under the curve (AUC 0.625, p < 0.001) than the other three scales (AUC Increased scores on these neuropathy scales (NSS, NDS, TCSS, and MNSI) and NCV were significantly associated with increased risk of MI and were considered independent risk factors.

Bone marrow adiposity in diabetes and clinical interventions.

This study aims to review bone marrow adipose tissue (BMAT) changes in people with diabetes, contributing factors, and interventions. In type 1 diabetes (T1D), BMAT levels are similar to healthy controls, although few studies have been performed. In type 2 diabetes (T2D), both BMAT content and composition appear altered, and recent bone histomorphometry data suggests increased BMAT is both through adipocyte hyperplasia and hypertrophy. Position emission tomography scanning suggests BMAT is a major source of basal glucose uptake. BMAT is responsive to metabolic interventions. BMAT is a unique fat depot that is influenced by metabolic factors and proposed to negatively affect the skeleton. BMAT alterations are more consistently seen in T2D compared to T1D. Interventions such as thiazolidinedione treatment may increase BMAT, whereas metformin treatment, weight loss, and exercise may decrease BMAT. Further understanding of the role of BMAT will provide insight into the pathogenesis of diabetic bone disease and could lead to targeted preventive and therapeutic strategies.

Remotely Conducted App-Based Intervention for Cardiovascular Disease and Diabetes Risk Awareness and Prevention Single-Group Feasibility Trial.

Cardiovascular disease and type 2 diabetes mellitus are two of the most prevalent chronic conditions worldwide. An unhealthy lifestyle greatly contributes to someones risk of developing these conditions. Mobile health is an emerging technology that can help deliver health promotion interventions to the population, for example, in the form of health apps. The aim of this study was to test the feasibility of an app-based intervention for cardiovascular and diabetes risk awareness and prevention by measuring nonusage, dropout, adherence to app use, and usability of the app over 3 months. Participants were eligible if they were aged 45 years or older, resided in Australia, were free of cardiovascular disease and diabetes, were fluent in English, and owned a smartphone. In the beginning, participants received an email with instructions on how to install the app and a user guide. After 3 months, they received an email with an invitation to an end-of-study survey. The survey included questions about general smartphone use and the user version of the Mobile Application Rating Scale. We analyzed app-generated and survey data by using descriptive and inferential statistics as well as thematic analysis for open-text comments. Recruitment took place between September and October 2021. Of the 46 participants who consented to the study, 20 (44%) never used the app and 15 (33%) dropped out. The median age of the app users at baseline was 62 (IQR 56-67) years. Adherence to app use, that is, using the app at least once a week over 3 months, was 17% (846) of the total sample and 31% (826) of all app users. The mean app quality rating on the user version of the Mobile Application Rating Scale was 3.5 (SD 0.6) of 5 points. The app scored the highest for the information section and the lowest for the engagement section of the scale. Nonusage and dropouts were too high, and the adherence was too low to consider the intervention in its current form feasible. Potential barriers that we identified include the research team not actively engaging with participants early in the study to verify that all participants could install the app, the intervention did not involve direct contact with health care professionals, and the app did not have enough interactive features.

The Influence of Wearables on Health Care Outcomes in Chronic Disease Systematic Review.

Chronic diseases contribute to high rates of disability and mortality. Patient engagement in chronic disease self-management is an essential component of chronic disease models of health care. Wearables provide patient-centered health data in real time, which can help inform self-management decision-making. Despite the perceived benefits of wearables in improving chronic disease self-management, their influence on health care outcomes remains poorly understood. This review aimed to examine the influence of wearables on health care outcomes in individuals with chronic diseases through a systematic review of the literature. A narrative systematic review was conducted by searching 6 databases for randomized and observational studies published between January 1, 2016, and July 1, 2021, that included the use of a wearable intervention in a chronic disease group to assess its impact on a predefined outcome measure. These outcomes were defined as any influence on the patient or clinician experience, cost-effectiveness, or health care outcomes as a result of the wearable intervention. Data from the included studies were extracted based on 6 key themes, which formed the basis for a narrative qualitative synthesis. All outcomes were mapped against each component of the Quadruple Aim of health care. The guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement were followed in this study. A total of 30 articles were included studies reported 2446 participants (mean age range 10.1-74.4 years), and the influence of 14 types of wearables on 18 chronic diseases was presented. The most studied chronic diseases were type 2 diabetes (430, 13%), Parkinson disease (330, 10%), and chronic lower back pain (330, 10%). The results were mixed when assessing the impact on a predefined primary outcome, with 50% (1530) of studies finding a positive influence on the studied outcome and 50% (1530) demonstrating a nil effect. There was a positive effect of 3D virtual reality systems on chronic pain in 7% (230) of studies that evaluated 2 distinct chronic pain syndromes. Mixed results were observed in influencing exercise capacity weight and biomarkers of disease, such as hemoglobin A Given their popularity and capability, wearables may play an integral role in chronic disease management. However, further research is required to generate a strong evidence base for safe and effective implementation. PROSPERO International Prospective Register of Systematic Reviews CRD42021244562 httpswww.crd.york.ac.ukprosperodisplayrecord.phpRecordID244562.

Prioritizing the glucose-lowering medicines for type 2 diabetes by an extended fuzzy decision-making approach with target-based attributes.

Different therapeutic classes have been authorized for the treatment of hyperglycemia in type 2 diabetic patients, and even more drug classes are under development. This variety of alternative treatments and the general treatment algorithms of the clinical guidelines lead to a nonuniform prescription of drugs by endocrinologists and diabetic specialists. Diabetes medication choice is a multi-objective problem with many difficulties in making rational decisions because of the wide range of hyperglycemia-lowering agents with multiple benefits and multiple risk elements. This paper proposes a group Entropy-CRiteria Importance Through Inter-criteria Correlation (CRITIC)-Weighted Aggregated Sum Product ASsessment (WASPAS) multi-criteria decision-making (MCDM) model with target-based criteria to prioritize and rank the glucose-lowering medicines for type 2 diabetes using the American Diabetes Association and International Diabetes Federation Clinical Guidelines. The proposed model consists of a weighting method comprising both objective and subjective approaches the two most common objective approaches (i.e., Entropy and CRITIC methods) are used to find the objective weights. Then, these weights are aggregated with the subjective weights that endocrinologists assign to the criteria. Afterward, a WASPAS target-based method is developed to provide the final ranking of the medications. Finally, the close correlation between the final ranking of the proposed methodology and the average priority order of the medications obtained by different MCDM methods implies the strength and validity of the model performance.

Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes results from UK primary care electronic health records.

Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes. We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means. The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index 0.659, 95% CI 0.654-0.663) as compared with using last observed values (C-index 0.651, 95% CI 0.646-0.656) or means (C-index 0.650, 95% CI 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase 0.005, 95% CI 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index increase 0.002, 95% CI 0.000-0.003), HbA1c (C-index increase 0.002, 95% CI 0.000-0.003) or HDL cholesterol (C-index increase 0.003, 95% CI 0.002-0.005). Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.

New-Onset Atrial Fibrillation in Patients With Type 2 Diabetes Treated With Novel Glucose-Lowering Therapies.

Whether sodium-glucose cotransporter 2 inhibitors (SGLT2is) are associated with lower risk of new-onset atrial fibrillation (AF) compared with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes was unknown. We aimed to determine the comparative risk of new-onset AF with SGLT2is vs GLP-1RAs in Asian patients with type 2 diabetes in a real-world setting. We used medical data from a multicenter health care provider in Taiwan and enrolled 16 566 and 2746 patients treated with an SGLT2i and a GLP-1RA, respectively, from January 1, 2016, to December 31, 2018. Propensity score weighting was used to balance the baseline covariates. The patients were followed from the drug index date until the occurrence of new-onset AF or the end of the follow-up period. In this study, 54%, 45%, and 1% of the SGLT2i group patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively, and 65% and 35% of the GLP-1RA group patients were treated with liraglutide and dulaglutide, respectively. SGLT2is were associated with lower risk of new-onset AF compared with GLP-1RAs after inverse probability of treatment weighting (subdistribution hazard ratio 0.72 95% CI, 0.54-0.97 P 0.028). Subgroup analysis revealed that this finding was consistent among the following high-risk subgroups older patients, female patients, and patients with cardiovascular disease or chronic kidney disease. SGLT2is were associated with lower risk of new-onset AF compared with GLP-1RAs among patients with type 2 diabetes mellitus in a real-world practice.

Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats.

Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage. We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-α, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma. The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-α levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p < 0.0001). This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment.

Effectiveness of an integrated primary care intervention in improving psychosocial outcomes among Latino adults with diabetes the LUNA-D study.

To compare the effectiveness of usual care (UC) versus a culturally tailored integrated care model in improving mental health symptoms for Latino patients with Type 2 diabetes mellitus (T2DM). We conducted a two-arm randomized controlled trial from 2015 to 2019 at a federally qualified health center. Participants were 456 adults ages 23-80 years who had a previous diagnosis of T2DM and were not currently using insulin. Participants were randomly assigned to Integrated Care Intervention (ICI including behavioralmental healthcare, medical visits, health education and care coordination) or UC standard of care including referrals for health education and behavioralmental health care where appropriate. Intention-to-treat, multilevel models were used to compare group × time changes in depression and anxiety symptoms (PHQ-8 GAD-7) and perceived stress (PSS-10) across 6 months. Participant mean age was 55.7 years, 36.3% were male, and 63.7% were primarily Spanish speaking. Baseline sociodemographic factors and mental health symptoms across study arms were balanced. Significant group × time interaction effects were observed for anxiety and depression symptoms (p < .05). Within the ICI and UC groups, mean depression symptom changes were -0.93 and -0.39 (p < .01) anxiety symptom changes were -0.97 (p < .01) and -0.11 (p .35) and perceived stress changes were -1.56 and -1.27 (p < .01), respectively. Although both ICI and UC showed decreases over time, the ICI group evidenced larger, statistically significant changes in both depression and anxiety. Adapted integrated models of behavioral and chronic disease management appear to be effective and could be considered for usual care practices. NCT03983499. We developed and tested a culturally adapted, enhanced service (“Integrated Care Intervention”) for Latino patients with Type 2 diabetes (T2D) to support their physical and mental health. The Integrated Care Intervention included receiving mental healthcare (i.e., “behavioral healthcare”) services and health education during a routine appointment. Patients receiving the Integrated Care Intervention were compared to patients receiving standard primary care services (i.e., “Usual Care”), which may include a referral for health education and behavioral health services if their provider feels it is warranted. The study was conducted from 2015 to 2019 at a community health center. Study participants were 456 adults ages 23–80 years who had a previous diagnosis of T2D and were not currently using insulin. Participants were randomly assigned to an Integrated Care Intervention group or Usual Care group. We compared changes in depression and anxiety symptoms and perceived stress over a 6-month period for the two study participant groups. Patients assigned to the Integrated Care Intervention group showed larger improvements in both depression and anxiety symptoms over 6 months than the patients assigned to the Usual Care group. These findings indicate that Latino patients may benefit from receiving both behavioral and chronic disease management services during routine visits with their primary care provider.

Cardiorespiratory fitness in a population with different glucose metabolic statuses low cardiorespiratory fitness increases the risk of early abnormal glucose metabolism.

Low cardiorespiratory fitness (CRF) is a risk factor for many chronic diseases. This study aimed to evaluate the CRF of a sample of adults with different glucose tolerance statuses to explore its relationship with early abnormal glucose metabolism according to sex. A total of 93 participants were assigned to three groups, i.e. the normal glucose tolerance (NGT) group, impaired glucose regulation (IGR) group and new-onset type 2 diabetes mellitus (T2DM) group, through an oral glucose tolerance test. Cardiopulmonary exercise testing was performed to evaluate the participants CRF. The physical measurements (including height, weight, systolic blood pressure SBP and diastolic blood pressure) and laboratory test results (including fasting plasma glucose and two-hour plasma glucose 2h-PG) of all participants were collected. Partial correlation, multiple linear regression (stepwise method) and logistic regression were used to analyse the data. Compared to the males with NGT, those with T2DM or IGR had a lower exercise time (P 0.044), anaerobic threshold (AT) oxygen uptake (VO2) (P 0.009), maximum VO2kg (P 0.041) and oxygen uptake efficiency slope (P 0.002). The male participants with T2DM had lower AT power (P 0.001) than those with IGR or NGT. Compared to the females with NGT, the AT heart rate (HR) (P 0.003), AT SBP (P 0.002) and maximum VO2kg (P 0.039) were lower in the female T2DM and IGR groups. The multiple linear regression (stepwise method) analyses showed that the maximum VO2kg (β -0.268, p 0.026) and one-minute HR recovery (β -0.239, p 0.039) of the females improved the prediction of the 2h-PG when entered in the model. The logistic analysis results indicated that the VO2 max of the male participants was related to pre-diabetes (β -0.003, p 0.024) and that their AT power was associated with new-onset diabetes (β -0.053, p 0.010). Meanwhile, the AT SBP of the female participants was related to pre-diabetes (β 0.120, p 0.019), and their AT HR was related to new-onset diabetes (β -0.102, p 0.014). Low CRF is associated with abnormal glucose metabolism. The CRF is closely associated with the 2h-PG after glucose load and is an important risk factor for pre-diabetes and new-onset diabetes.

Efficacy of the Diabetes Prevention Program Group Lifestyle Balance Program Modified for Individuals with TBI (GLB-TBI) Results from a 12-month Randomized Controlled Trial.

Obesity after traumatic brain injury (TBI) is a public health issue and no evidence-based weight loss interventions exist to meet the unique needs of individuals after TBI. To (a) examine the efficacy of the Diabetes Prevention Program Group Lifestyle Balance for TBI (GLB-TBI) weight-loss intervention compared to an attention control for primary (weight-loss) and secondary health outcomes (b) determine participant compliance with the GLB-TBI and (c) determine if compliance is associated with improved outcomes. Individuals with moderate to severe TBI, age 18-64 years, ≥6 months postinjury, and body mass index of ≥25 kgm2 were randomized to a 12-month, 22-session GLB-TBI intervention or attention control condition. Weight-loss (lbs.), anthropometric, biomarkers, and patient-reported outcomes were collected at baseline, 3, 6, and 12 months. The GLB-TBI group (n 27) lost 17.8 ± 41.4lbs (7.9%) over the 12-month program and the attention control group (n 27) lost 0 ± 55.4lbs (0%). The GLB-TBI group had significant improvements in diastolic blood pressure, triglycerides, and HDL cholesterol. GLB-TBI attendance was 89.6% and weekly self-monitoring of diet and activity was 68.8%. Relative to baseline, the GLB-TBI compliant group (≥80% attendance ≥85% self-monitoring n 10) had a statistically significant decrease in weight at each assessment, the noncompliant group had a significant decrease between 6 and 12 months (n 17), with no change in weight in the attention control group (n 27). Findings suggest for adults with TBI who are overweight or obese, participation in the GLB-TBI can significantly reduce weight and metabolic risk factors and increase self-reported habits for diet and exercise.

GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1.

Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4). To determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4. Single-site study conducted at an academic medical center of 20 nondiabetic subjects and 13 subjects with type 2 diabetes. This was a crossover study in which subjects received either a DPP4 inhibitor (DPP4i sitagliptin) or placebo on 2 separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin9-39 (Ex-9) and saline. The main outcome measures were arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg). Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both α- and β-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by 14% (P < .03 for both groups). Sitagliptin lowered baseline glycemia but did not affect the primary measures of insulin secretion. However, a significant interaction between sitagliptin and Ex-9 suggested more GLP-1r activation with DPP4i treatment in subjects with diabetes. GLP-1r activation contributes to β-cell secretion in diabetic and nondiabetic people during α-cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of β-cells by paracrine signals from α-cells. This process may be affected by DPP4 inhibition.

Epigallocatechin-3-gallate ameliorates renal endoplasmic reticulum stress-mediated inflammation in type 2 diabetic rats.

Epigallocatechin-3-gallate (EGCG), an essential polyphenolic constituent found in tea leaves, possesses various potent biological activities. This research was undertaken to investigate the impact of EGCG against endoplasmic reticulum (ER) stress-mediated inflammation and to clarify the underlying molecular mechanism in type 2 diabetic kidneys. The male rats were randomized into four groups normal, diabetic, low-dose EGCG, and high-dose EGCG. In type 2 diabetic rats, hyperglycemia and hyperlipidemia noticeably caused renal structural damage and dysfunction and aggravated ER stress. Meanwhile, sustained ER stress activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and then upregulated the contents of inflammatory cytokines in the diabetic kidney. Following supplementation with 40 mgkg and 80 mgkg EGCG, hyperglycemia, hyperlipidemia, and renal histopathological alterations and dysfunction were noticeably ameliorated renal ER stress, NLRP3 inflammasome, and inflammatory response were markedly repressed in the EGCG treatment groups. In summary, the current study highlighted the renoprotective effects of EGCG in type 2 diabetes and its mechanisms are mainly associated with the repression of ER stress-mediated NLRP3 inflammasome overactivation.

Combined effects of voluntary running and liraglutide on glucose homeostasis, fatty acid composition of brown adipose tissue phospholipids, and white adipose tissue browning in dbdb mice.

There is a potential therapeutic application targeting brown adipose tissue (BAT). Either voluntary running or liraglutide increases the thermogenesis of BAT in type 2 diabetes mellitus, but their combined effect is not yet clarified. Male leptin receptor-deficient dbdb diabetic mice (n 24) were randomly divided into voluntary running, liraglutide, voluntary running liraglutide, and control groups (n 6group). Normal male C57 mice were the negative control (n 6). Fasting blood glucose was monitored every week, plasma insulin and lipid profiles were analyzed, and thermogenic protein expression in BAT and white adipose tissue (WAT) were analyzed by the western blot. A total of 128 metabolites associated with phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, and ceramides were targeted in BAT. Compared to the control group, voluntary running or liraglutide treatment significantly lowered the blood glucose and increased the insulin level the combined group showed a better effect than liraglutide alone. Hence, the combined treatment showed an enhanced hypoglycemic effect. Uncoupling protein 1 (UCP1) and OXPHOS protein expression in BAT and UCP1 in WAT were significantly increased after exercise training and liraglutide treatment. However, BAT metabolomics showed that compared to the control mice, nine fatty acids increased in the exercise group, six increased in the liraglutide group, and only three increased in the combined group. These results may suggest a higher hypoglycemic effect and the activation of BAT and WAT browning in the combined group.

Peroxisome Proliferator-Activated Receptors as Superior Targets for Treating Diabetic Disease, Design Strategies - Review Article.

Thiazolidinedione (TZD), a class of drugs that are mainly used to control type 2 diabetes mellitus (T2DM), acts fundamentally as a ligand of peroxisome proliferator-activated receptors (PPARs). Besides activating pathways responsible for glycemic control by enhancing insulin sensitivity and lipid homeostasis, activating PPARs leads to exciting other pathways related to bone formation, inflammation, and cell proliferation. Unfortunately, this diverse effect of activating several pathways may show in some studies adverse health outcomes as osteological, hepatic, cardiovascular, and carcinogenic effects. Thus, a silver demand is present to find and develop new active and potent antiglycemic drugs for treating T2DM. To achieve this goal, the structure of TZD for research is considered a leading structure domain. This review will guide future research in the design of novel TZD derivatives by highlighting the general modifications conducted on the structure component of TZD scaffold affecting their potency, binding efficacy, and selectivity for the control of T2DM.

Clinical Utility of Cardiovascular Risk Scores for Identification of People With Type 2 Diabetes More Likely to Benefit From Either GLP-1 Receptor Agonist or SGLT2 Inhibitor Therapy.

Differentiation of risk for major adverse cardiovascular events (MACE) from heart failure hospitalization (HHF) or kidney disease is important when selecting glucose-lowering therapy. We investigated the ability of separate MACE and HHF risk scores to 1) differentiate MACE from HHF risk and 2) identify individuals more likely to benefit from either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2is). We identified three trials in type 2 diabetes that reported cardiovascular outcomes stratified by Thrombolysis In Myocardial Infarction Risk Scores for MACE and HHF. Pooled placebo-arm rates of HHF, MACE, and their ratio and estimated GLP-1RA- and SGLT2i-mediated reductions in events (MACE and HHF combined) were compared across cardiovascular risk strata in the trial populations. The HHF rate was less frequent than MACE at all risk levels but increased from 18% of the MACE rate at low-intermediate HHF risk to 61% at highest HHF risk. Similarly, with increasing MACE risk, the incidence of HHF increased from 19% of the MACE incidence in those at low MACE risk to 51% in those with the highest MACE risk. Estimated GLP-1RA- and SGLT2i-mediated reductions in cardiovascular events were similar in those at low-intermediate MACE or HHF risk but tended to favor SGLT2is at higher risk levels of both scores. A greater increase in the rate of HHF relative to MACE was observed with progressively higher cardiovascular risk, regardless of the risk score applied. Consequently, SGLT2is may offer greater overall cardiovascular protection in those at highest MACE risk, not just those at highest HHF risk.

Hansens disease and COVID-19 co-infection in Brazil.

The implications of COVID-19 co-infection in patients under treatment for Hansens disease (HD, leprosy) remain uncertain. We aimed to describe clinical characteristics, treatments, and outcomes in patients with HD and COVID-19 in Brazil. Cross-sectional study recruiting adult HD patients with PCR-confirmed COVID-19 from five HD treatment centers in Brazil between March 1, 2020, and March 31, 2021. At the time of this study, no patient had received COVID-19 vaccine. Of 1377 patients under treatment for HD, 70 (5.1%) were diagnosed with COVID-19. Of these, 41 (58.6%) had PCR-confirmed COVID-19, comprising 19 men and 22 women, aged 24-67 (median 45) years. HD was multibacillary in 3941 patients. Eight patients ceased WHO Multi-Drug Therapy for HD, three for lack of drugs, two because of COVID-19, and three for other reasons. Of the 33 who continued treatment, 26 were on the standard regimen and seven an alternative regimen. Seventeen patients were receiving oral prednisone, including nine patients with type 1 reaction, four with type 2 reaction, three with neuritis, and one with rheumatologic disease. Twelve patients were hospitalized for COVID-19, and six patients died, of whom three had hypertension and one also had type 2 diabetes and obesity. COVID-19 and Hansens disease co-infection did not appear to change the clinical picture of either disease in this cross-sectional study. The wider impact of the pandemic on persons affected by HD requires follow-up and monitoring.

Diabetes how to manage overweight and obesity in type 2 diabetes mellitus.

The prevalence of obesity worldwide continues to increase substantially. Obesity is a chronic disease that can lead to other health conditions, including type 2 diabetes mellitus (T2DM). A variety of treatment options are available to treat T2DM. With its prevalence increasing, it is essential that healthcare professionals assess how their patients current diabetes treatment is being managed to avoid further weight gain in those with overweight or obesity.

Diabetes how to manage cardiovascular risk in secondary prevention patients.

Atherosclerotic cardiovascular disease (ASCVD) commonly affects people with type 2 diabetes (T2D). Historically, traditional cardiovascular (CV) risk-lowering therapies in patients with T2D and ASCVD have included antiplatelet agents, blood pressure-lowering therapies, lipid-lowering therapies and healthy lifestyle modifications. In the past decade, multiple antihyperglycaemic agents have emerged as CV risk-lowering therapies in this population as well. This article provides a narrative review on the current non-glycaemic and glycaemic treatment options for CV risk reduction in patients with T2D and ASCVD. The FDA requirement that all new antihyperglycaemic agents undergo cardiovascular outcomes trials has demonstrated increasing evidence to support the role of glucagon-like peptide 1 (GLP1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors as first-line agents for both glycaemic control and CV risk reduction in this population.

Diabetes how to manage chronic kidney disease.

Chronic kidney disease (CKD) is a prevalent and progressive condition worldwide, and diabetes is a leading risk factor of this renal disorder. People with diabetes and CKD are at high risk of complications such as cardiovascular events and death. CKD is often unrecognized and undiagnosed amongst people with diabetes. To manage CKD, multiple existing and newer agents have been studied in trials and recommended in clinical practice guidelines. A narrative review of primary andor secondary renal outcomes from randomized, controlled trials is summarized in this article. The main objective was to provide the most up-to-date information regarding existing and new pharmacotherapy for the management of CKD amongst people with diabetes, specifically type 2 diabetes (T2D). Traditional agents, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been used for 20 years to preserve kidney function. Other existing agents have received approval by the FDA for the management of CKD such as dapagliflozin, with a role in reducing intraglomerular pressure. Evidence with sodium-glucose cotransporter 2 inhibitors show a potential class effect on improving renal outcomes, independent on their effect on glycaemic parameters. Recently, finerenone was approved for people with T2D and CKD based on clinical evidence as a non-steroidal mineralocorticoid receptor antagonist. Overall, primary and secondary prevention trials have influenced changes in clinical practice guidelines regarding the use of existing and new pharmacotherapy for CKD. Additional considerations include lifestyle modifications, blood pressure management and achievement of glycaemic targets for people with diabetes and CKD, following adequate screening of glomerular filtration rate andor severity of albuminuria. Due to more robust evidence, clinical practice guidelines have been modified to reflect high-level recommendations for the management of CKD in people with diabetes, specifically T2D. Additional evidence is needed amongst people with lower glomerular filtration rates and in comparison with the standard of care.

Diabetes the role of continuous glucose monitoring.

Diabetes mellitus is a chronic condition affecting 1 out of every 11 people worldwide. Monitoring of blood glucose allows for therapeutic lifestyle and pharmacotherapy changes to reduce the occurrence of hyperglycaemia and hypoglycaemia. Advancements in technology over the past two decades have increased patient and clinician access to glucose data and trends with continuous glucose monitoring (CGM) systems. This narrative review seeks to investigate the efficacy and safety of CGM for the management of diabetes. In type 1 diabetes (T1DM) and type 2 diabetes, efficacy studies of real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) have shown a decrease in HbA1C (0.3-0.6%) over traditional self-monitoring blood glucose. Percent time in the target glucose range also improved (6.8-17.6%). Rates of hypoglycaemia, including severe hypoglycaemia, decreased in studies of rtCGM and isCGM with most available data in T1DM. In pregnant women with T1DM, rtCGM has shown modest improvements in HbA1C and time in target glucose range and decreased risk of neonatal complications. Multiple studies have shown that the use of rtCGM or isCGM increased diabetes treatment satisfaction amongst patients. Head-to-head studies of rtCGM and isCGM are limited but one study indicates that a CGM system with alarms may be preferred in T1DM to reduce the risk of hypoglycaemia. Selection of a CGM device should depend on patient-specific factors and insurance coverage. The results of one study show that the benefits of CGM device use were not sustained after discontinuing use. Increasing widespread and long-term access to CGM devices is necessary to improve the management of diabetes amongst the greater population.

Diabetes how to manage patients experiencing hypoglycaemia.

Hypoglycaemia is a complication associated with the management of both type 1 and type 2 diabetes. Despite newer technologies to help minimize the risk of hypoglycaemia, it remains a barrier for some patients to achieve optimal glycaemic control. In this review, the definitions and risk factors for hypoglycaemia will be briefly discussed and an in-depth review of the management for a conscious or unconscious patient in the outpatient and inpatient settings is provided. Rapid-acting glucose is the preferred treatment for a conscious patient regardless of the setting. For an unconscious patient, glucagon is preferred if the patient does not have intravenous (IV) access and dextrose can be used for patients with IV access. Until recently, there was only one formulation of glucagon, which had limitations due to the multiple steps required for reconstitution prior to administration in an emergency setting. This review also discusses the different glucagon formulations currently available for the management of hypoglycaemia.

Relationship Between Psychological Needs and Regulatory Focus Among Adults with Type 2 Diabetes.

Diabetes is a chronic disease. A sustained change in lifestyle is generally necessary for terms of diet and physical activity. According to Self-Determination Theory, the nature of the motivation to regulate ones behavior is linked to the satisfaction of three psychological needs autonomy, competence, and relatedness. According to Regulatory Focus Theory, there is a promotion focus and a prevention focus. The prevention focus has been shown to have a different relationship with the satisfaction of the needs of the Self-Determination Theory between a general population and a population with health problems. This study investigates the relationship between psychological needs and regulatory focus for people with type 2 diabetes (T2D). 295 adults with T2D completed an online questionnaire measuring autonomy and perceived competence and regulatory focus. The promotion focus predicts the satisfaction of needs for autonomy and competence ( These factors display different relationships between them among people with type 2 diabetes compared to the general population. Prevention focus seems to be more beneficial in the specific context of T2D than in the general population.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Diabetes Mellitus A Diagnostic Dilemma.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological disorder of the peripheral nerves which can lead to gradually increasing motor and sensory loss. It can be a difficult entity to diagnose, particularly in elderly patients with a history of Diabetes Mellitus due to their overlapping neuropathic syndromes. Reported is a case of CIDP in an elderly female who manifested multiple sensory, motor, and autonomic complaints. A compilation of clinical features, neuroimaging, lumbar puncture, electromyography, nerve conduction studies, and nerve biopsy were used to reach the diagnosis. Highlighted is a clinical approach to identifying CIDP that can cause neuropathy in the setting of other potential confounding disorders namely Diabetes Mellitus.

Metabolomics and biochemical insights on the regulation of aging-related diabetes by a low-molecular-weight polysaccharide from green microalga

Globally, aging and diabetes are considered prevalent threats to human health.

A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study.

Hyper-caloric intake of saturated fatty acids (SFAs) is common in modern societies, probably contributing to the epidemic of type 2 diabetes mellitus (T2DM). This study conducted two randomized controlled trials (RCTs) for developing a new indicator that can assess the nutritional status and examined its association with incidence of T2DM. In RCT 1, healthy participants were randomly assigned into three groups, namely, control group ( In RCT 1, serum fatty acids, including C140 and C180, increased, whereas C182, C204, C225, and C226 decreased serum amino acids, including tyrosine, alanine, and aminobutyric acid, increased, whereas histidine and glycine decreased ( The newly developed indicator in RCTs can be used in assessing the nutritional status of hypercaloric intake of SFA and predicting the development of T2DM.

Comparison of Blood Pressure Variability between 24 h Ambulatory Monitoring and Office Blood Pressure in Diabetics and Nondiabetic Patients A Cross-Sectional Study.

Evidence regarding blood pressure (BP) variability (BPV) and its independent association with adverse outcomes has grown. Diabetic patients might have increased BPV, but there is still an evidence gap regarding relation between BPV and type 2 diabetes beyond mean values of BP. To examine the relationship between 24 h ambulatory BP monitoring (ABPM, short-term variability) and visit-to-visit in-office BPV (OBP, long-term variability), in diabetics ( We conducted a single-center cross-sectional study in an outpatient BP unit, including adult patients consecutively admitted from 1999 to 2019. Multivariate was performed to compare BPV between A total of 1123 patients with ABPM and OBP measurements were included. Values of eGFR and PWV were worse in We found that diabetes is associated with higher variability of daytime BP than nondiabetics along with worse damage of vascular and renal function. However, in contrast to nondiabetics, in diabetics eGFR and PWV may not be dependent on BP variability, suggesting that other mechanisms might explain more rigorously the greater damage of target organ lesion markers.

Exocytosis Proteins Typical and Atypical Mechanisms of Action in Skeletal Muscle.

Insulin-stimulated glucose uptake in skeletal muscle is of fundamental importance to prevent postprandial hyperglycemia, and long-term deficits in insulin-stimulated glucose uptake underlie insulin resistance and type 2 diabetes. Skeletal muscle is responsible for 80% of the peripheral glucose uptake from circulation

Health consequences of early-onset compared with late-onset type 2 diabetes mellitus.

Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus (T2DM) conferred on patients a broader tendency for complications beyond vascular ones, a comprehensive analysis of patterns of complications across all relevant systems is currently lacking. We prospectively studied 1 777 early-onset (age at diagnosis ≤ 45 years) and 35 889 late-onset (>45 years) T2DM patients with matched unexposed individuals from the UK Biobank. Diabetes-specific and -related complications were examined using phenome-wide association analysis, with patterns identified by comorbidity network analysis. We also evaluated the effect of lifestyle modifications and glycemic control on complication development. The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years, respectively. Compared to late-onset T2DM patients, patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs hazard ratio (HR) 3.46 vs. 1.72, the endocrinemetabolic system (HR 3.08 vs. 2.01), and the neurological system (HR 2.70 vs. 1.81). Despite large similarities in comorbidity patterns, a more complex and well-connected network was observed for early-onset T2DM. Furthermore, while patients with early-onset T2DM got fewer benefits (12.67% reduction in pooled HR for all studied complications) through fair glycemic control (median HbA Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM. Aggressive glucose-lowering intervention, complemented by lifestyle modifications, are feasible strategies for controlling early-onset T2DM-related complications.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxia. The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020. This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005. The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ngml and a range of HIF-1α values in vascular complications (0.52- 8.87) mgdL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005). HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

IDegLira Improves Metabolic Control in Patients with Type 2 Diabetes Previously Treated with Premix Insulin.

IDegLira( fixed combination of GLP 1 receptor agonist and insulin) has been shown to be effective in improving the glucoregulation in patients previously treated with oral therapy as well as individual components, GLP-1 receptor agonist or basal insulin. The aim of this study is to examine the parameters of metabolic control in patients treated with IDegLira who were previously treated with premix insulin in several daily doses and to compare them with patients whose premix insulin dose was increased. The study included 100 patients who had been previously treated with two or three daily doses of premix insulin. Half of the patients were switched to IdegLira( group I), and half (group II) had their insulin dose increased according to the clinical assessment of the physician. Fasting glucose, 2h postprandial glucose, HbA1c, BMI and insulin dose were determined at baseline and at follow-up after 6 months. Patients treated with IDegLira compared to patients whose insulin dose was increased achieved significantly lower fasting glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p <0.001), BMI (p <0.001) with a significantly lower insulin dose (p <0.001). Comparison of the same parameters within the groups of patients at the beginning and after 6 months showed that patients who were switched from insulin premix to IDegLira achieved significantly lower fasting blood glucose (p <0.001), postprandial glucose (p <0.001), HbA1c (p < 0.001), BMI (p <0.001) with significantly lower insulin dose within the fixed combination (p <0.001). Patients with gradually increased insulin dose achieved significant reduction in fasting glucose (p 0.021) and postprandial glucose (p 0.036),but with a significantly higher insulin dose (p 0.005). There was also a slight increase in BMI that was not statistically significant (p 0.267). The obtained data suggest that switching patients from a complex insulin regimen to a fixed combination of basal insulin and GLP 1 receptor agonist in comparison to increases in insulin dose results in a significant improvement in fasting glucose, postprandial glucose, HbA1c, and BMI. The results were achieved with a significantly lower daily insulin dose.

The agreement between measured HbA1c and optimized target HbA1c based on the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) A cross-sectional study of elderly patients with diabetes.

To investigate the achievement of individualized target HbA1c based on the Japanese guideline after geriatric assessment with the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) and to evaluate patient characteristics acting as barriers to achieving the target HbA1c in elderly outpatients with diabetes. This cross-sectional study enrolled 303 Japanese outpatients aged ≥65 years with diabetes. Their health status was measured using the DASC-8. The target HbA1c was optimized for each patient by the guideline based on the DASC-8 score and use of drugs potentially associated with severe hypoglycemia. Patient characteristics related to the agreement between measured HbA1c and target HbA1c were extracted by multivariate logistic regression analysis. The mean age was 73.0 years and the mean body mass index (BMI) was 24.2 kgm The agreement between measured HbA1c and target HbA1c was low in elderly patients with diabetes. Geriatr Gerontol Int 2022 22 560-567.

Diagnostic Puzzle of Acute Ischemic Stroke Mimics - Seizure Versus Post-Stroke Recrudescence A Case Report.

BACKGROUND Focal seizure with impaired awareness, post-seizure Todds phenomenon, and post-stroke recrudescence can all present with focal neurological deficits, mimicking stroke. As acute ischemic stroke mimics, they are distractors in the emergency setting where management is time-sensitive both for seizure and stroke. Nevertheless, a timely diagnosis can be made with exploration of the clinical features supported by investigation such as computerized tomographic perfusion. CASE REPORT Our patient was a 65-year-old woman who was known hypertensive, with type 2 diabetes mellitus, and previous intracerebral hemorrhage with minimal right-sided residual deficits, but still able to ambulate independently. She was brought to the Emergency Department because 1 hour prior to presentation, she had sudden worsening of weakness of the right limbs, aphasia, aggression, and confusion. An initial impression of repeat acute stroke, focal seizure with impaired awareness, Todds phenomenon, and post-stroke recrudescence was considered. While CT angiography was suggestive of left middle cerebral artery occlusion, CT perfusion revealed extensive hypoperfusion patterns beyond the region of the occlusion, thus suggesting a different etiology from acute ischemic stroke. In view of her previous left hemispheric lesion coupled with the presentation, our working diagnosis was seizure with Todds phenomenon, and she was started on an anti-epileptic drug. Her condition returned to baseline within 24 h of admission and was subsequently discharged. CONCLUSIONS Our case demonstrates that adequate elucidation of clinical features in conjunction with CT perfusion, as a dual-purpose tool, can aid the diagnosis of both stroke mimics and acute ischemic stroke in the Emergency Department where rapid treatment is essential.

Customized and Automated Machine Learning-Based Models for Diabetes Type 2 Classification.

This study aims to develop models to accurately classify patients with type 2 diabetes using the Practice Fusion dataset. We use Random Forest (RF), Support Vector Classifier (SVC), AdaBoost classifier, an ensemble model, and automated machine learning (AutoML) model. We compare the performance of all models in a five-fold cross-validation scheme using four evaluation measures. Experimental results demonstrate that the AutoML model outperformed individual and ensemble models in all evaluation measures.

Investigating Diabetes Mellitus Patients Experiences with Self Monitoring Blood Glucose Methods.

Diabetes mellitus (DM) is a common metabolic disease characterized by high blood glucose levels, and it is considered as a modern global threat. Glucose monitoring is an important component of modern therapy for diabetes mellitus. Self-monitoring blood glucose (SMBG) by finger pricking or flash glucose monitoring (FGM) allows individual planning of treatment. The aim of this study was to investigate patients experiences with self-monitoring blood glucose methods. A cross-sectional study was conducted using the Glucose Monitoring Experiences Questionnaire (GME-Q), consisted of 22 items with an overall score ranging from 1 to 5 (higher score indicates better experiences). The study included adult patients with diabetes mellitus type 1 (DM 1) or type 2 (DM 2). Out of 253 participants (mean age, 56.4 years), 65.6% were suffering from DM type 2 and 34.4% from DM type 1, whereas 48.6% were using SMBG and 49.8% FGM. The mean score of convenience and effectiveness were higher in the group of patients using FGM, while SMBG found to be more discreet. The results of the analysis suggested that there was no relation between gender and effectiveness, discreetness or convenience of the method used for glucose monitoring. Furthermore, participants with diabetes type 2 reported higher convenient and discreetness score than patients with diabetes type 1. The analysis also indicated that there was no relation between the age of the participants and the effectiveness, discreetness and convenience of any glucose monitoring method. Improved self-glucose monitoring experiences are an essential component to achieve effective management of patients suffering from both DM 1 and DM 2. More research should be conducted on the field of glucose monitoring experiences, related to the cost of the methods, the users training and the ability to support insulindiet calculations.

Investigating Diabetes Mellittus Impact on Various Aspects of Patients Quality of Life.

The aim of the study was to evaluate the quality of life (QoL) of patients with diabetes mellitus (DM) Methods A cross-sectional study was conducted using the Audit of Diabetes-Depended Quality of Life (ADDQoL) questionnaire. The study included adult patients with diabetes mellitus type 1 (DM 1) or type 2 (DM 2). Results A total of 253 patients were enrolled in the study. Despite the fact that the majority of participants stated a good QoL, DM has a negative impact on all 19 domains of ADDQoL. The greater negative impact referred to the domain freedom to eat. There was no relation between overall score of QoL and age, gender or type of DM. On the contrary, we found statistically significant relation between age, gender, type of DM, presence of comorbidities and specific domains of Qol. Conclusions Our findings, which are in accordance with the literature, highlight the great negative impact of DM on QoL of diabetics and they could be used by health professionals and policy makers to improve patients well-being.

Computational investigation of phytochemicals from

Type 2 diabetes mellitus remains global health challenge with involvement of both insulin resistance and dysfunctional insulin secretion from the pancreatic β-cell. Currently, peroxisome proliferator-activated receptor gamma (PPARγ) has been established to play a significant role in glucose homeostasis and insulin sensitization contributing to the pathogenesis of type 2 diabetes mellitus. Hence, this study used in-silico analysis to predict PPARγ antagonists from the natural compounds. ADMET screening, structure-based virtual screening and MMGBSA calculations of phytochemicals from HPLC analysis of

Surgical treatment on infective endocarditis impact of diabetes on mortality.

Type 2 diabetes mellitus (DM) is a frequent co-morbidity among patients suffering from infective endocarditis (IE). The aim of the study was to evaluate the impact of type 2 DM on the early-, intermediate- and long-term mortality of patients who underwent surgical treatment of endocarditis. We performed an observational cohort study in the large tertiary center in Israel during 14 years. All data of patients who underwent surgical treatment of endocarditis, performed between 2006 and 2020 were extracted from the departmental database. Patients were divided into two groups Group I (non-diabetic patients), and Group II (diabetic patients). The study population includes 420 patients. Group I (non-diabetic patients), comprise 326 patients, and Group II (diabetic patients), comprise 94 patients. Mean follow-up duration was 39.3 ± 28.1 months. Short-term, 30-day and in-hospital mortality, also intermediate-term mortality (1- and 3-year) was higher in the DM group compared with the non-DM group, but did not reach statistical significance 11.7% vs. 7.7%. (p 0.215) 12.8% vs. 8.3% (p 0.285) 20.2% vs. 13.2% (p 0.1) and 23.4% vs. 15.6% (p 0.09) respectively. Long-term, 5-year mortality was significantly higher in the DM group, compared to the non-DM group 30.9% vs. 16.6% (p 0.003). Furthermore, predictors for long-term mortality included diabetes (CI 1.056-2.785, p 0.029), as demonstrated by regression analysis. Diabetic patients have trend to increasing mortality at the short- and intermediate period post-surgery for IE, but this is not statistically significant. Survival of diabetic patients deteriorates after more than three years follow surgery. Diabetes is an independent predictor for long-term, 5-year mortality after surgical treatment of endocarditis, regardless of the patients age and comorbidities. Trial registration Ethical Committee of Sheba Medical Centre, Israel on 02.12. 2014, Protocol 4257.

Factors related to initial treatment for adhesive capsulitis in the medicare population.

Primary adhesive capsulitis (AC) is not well understood, and controversy remains about the most effective treatment approaches. Even less is known about the treatment of AC in the Medicare population. We aimed to fully characterize initial treatment for AC in terms of initial treatment utilization, timing of initial treatments and treatment combinations. Using United States Medicare claims from 2010-2012, we explored treatment utilization and patient characteristics associated with initial treatment for primary AC among 7,181 Medicare beneficiaries. Patients with primary AC were identified as patients seeking care for a new shoulder complaint in 2011, with the first visit related to shoulder referred to as the index date, an x-ray or MRI of the shoulder region, and two separate diagnoses of AC (ICD-9-CM codes 726.00). The treatment period was defined as the 90 days immediately following the index shoulder visit. A multivariable logistic model was used to assess baseline patient factors associated with receiving surgery within the treatment period. Ninety percent of beneficiaries with primary AC received treatment within 90 days of their index shoulder visit. Physical therapy (PT) alone (41%) and injection combined with PT (34%) were the most common treatment approaches. Similar patient profiles emerged across treatment groups, with higher proportions of racial minorities, socioeconomically disadvantaged and more frail patients favoring injections or watchful waiting. Black beneficiaries (OR 0.37, 0.16, 0.86) and those residing in the northeast (OR 0.36, 0.18, 0.69) had significantly lower odds of receiving surgery in the treatment period. Conversely, younger beneficiaries aged 66-69 years (OR 6.75, 2.12, 21.52) and 70-75 years (OR 5.37, 1.67, 17.17) and beneficiaries with type 2 diabetes had significantly higher odds of receiving surgery (OR 1.41, 1.03, 1.92). Factors such as patient baseline health and socioeconomic characteristics appear to be important for physicians and Medicare beneficiaries making treatment decisions for primary AC.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus a retrospective study from 2017 to 2021.

Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118244), 45.9% (112244) and 5.74% (14244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio OR 4.476 95% confidence interval CI 2.257-8.877 P < 0.001), an absence of diabetic retinopathy (OR 4.174 95% CI 2.049-8.502 P < 0.001), a high RBC count (OR 1.901 95% CI 1.251-2.889 P 0.003), and a negative of urinary glucose excretion test result (OR 2.985 95% CI 1.474-6.044 P 0.002).. A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

The gut microbiome as possible mediator of the beneficial effects of very low calorie ketogenic diet on type 2 diabetes and obesity a narrative review.

Several studies have shown a strong correlation between the different types of diets and gut microbiota composition on glycemia and weight loss. In this direction, low-carbohydrate and ketogenic diets have gained popularity, despite studies published so far leading to controversial results on subjects with diabetes. In this narrative review, firstly, we aimed to analyze the role of very-low-calorie ketogenic diets (VLCKDs) in type 2 diabetes (T2DM) and obesity management. Secondly, in this context, we focused attention on gut microbiota as a function of VLCKD, particularly in T2DM and obesity treatment. Finally, we reported all this evidence to underline the importance of gut microbiota to exalt new nutritional strategies for tailor-made management, treatment, and rehabilitation in subjects with T2DM and obesity, even with diabetic complications. In conclusion, this narrative review outlined the beneficial impact of VLCKD on gut microbiota even in subjects with T2DM and obesity, and, despite inner VLCKD short-duration feature allowing no sound-enough provisions for long-term outcomes, witnessed in favor of the short-term safety of VLCKD in those patients.Level of evidence Level V Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Variational autoencoders learn transferrable representations of metabolomics data.

Dimensionality reduction approaches are commonly used for the deconvolution of high-dimensional metabolomics datasets into underlying core metabolic processes. However, current state-of-the-art methods are widely incapable of detecting nonlinearities in metabolomics data. Variational Autoencoders (VAEs) are a deep learning method designed to learn nonlinear latent representations which generalize to unseen data. Here, we trained a VAE on a large-scale metabolomics population cohort of human blood samples consisting of over 4500 individuals. We analyzed the pathway composition of the latent space using a global feature importance score, which demonstrated that latent dimensions represent distinct cellular processes. To demonstrate model generalizability, we generated latent representations of unseen metabolomics datasets on type 2 diabetes, acute myeloid leukemia, and schizophrenia and found significant correlations with clinical patient groups. Notably, the VAE representations showed stronger effects than latent dimensions derived by linear and non-linear principal component analysis. Taken together, we demonstrate that the VAE is a powerful method that learns biologically meaningful, nonlinear, and transferrable latent representations of metabolomics data.

The 6-Month Efficacy of an Intensive Lifestyle Modification Program on Type 2 Diabetes Risk Among Rural Women with Prior Gestational Diabetes Mellitus a Cluster Randomized Controlled Trial.

This study aimed to evaluate the efficacy of an intensive lifestyle modification program tailored to rural Chinese women with prior gestational diabetes mellitus compared with usual care. In a cluster randomized controlled trial, 16 towns (clusters) in two distinct rural areas in China were randomly selected (8 towns per district) and 320 women with prior gestational diabetes mellitus were recruited from these towns. With stratification for the two study districts, eight towns (160 women) were randomly assigned to the intervention group of a tailored intensive lifestyle modification program and 8 towns (160 women) to the control group. Process measures were collected on attendance, engagement, fidelity, and satisfaction. Primary efficacy outcomes included glycemic and weight-related outcomes, while secondary efficacy outcomes were behavioral outcomes and type 2 diabetes risk score, which were collected at baseline, 3-month, and 6-month follow-up. Generalized estimation equations were used to analyze the data. High attendance (72% of sessions), engagement (67% of interactive activities and group discussions), fidelity (98%), and satisfaction (92%) with the tailored intensive lifestyle modification program were achieved. There were significant reductions in fasting blood glucose, oral glucose tolerance test 2 h, waist circumference, and type 2 diabetes risk score of participants in the intervention group compared to the control group (p < .05). There was no significant intervention effect on body mass index or behavioral outcomes (p > .05). In this study, we demonstrate the successful efficacy of an Intensive Lifestyle Modification Program in reducing type 2 diabetes risk among younger women with prior gestational diabetes mellitus. This tailored program delivered by local healthcare providers is a promising approach for diabetes prevention in rural China, reducing health disparities in rural communities about diabetes prevention. Registered in the Chinese Clinical Trial Registry (ChiCTR2000037956) on 3rd Jan 2018.

Prediction of all-cause and cardiovascular mortality using ankle-brachial index and brachial-ankle pulse wave velocity in patients with type 2 diabetes.

Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are used as non-invasive indicators for detecting atherosclerosis and arterial stiffness, two well-known predictors of mortality in patients with type 2 diabetes mellitus (T2DM). ABI and baPWV have independent associations with mortality however, their joint and interactive effects on mortality have not been assessed in patients with T2DM. This work aims to evaluate the independent, joint, and interactive associations of ABI and baPWV with all-cause and expanded cardiovascular disease (CVD) mortality in patients with T2DM. This observational study included 2160 patients with T2DM enlisted in the Diabetes Care Management Program database of China Medical University Hospital from 2001 to 2016 and then followed their death status until August 2021. Cox proportional hazard models were used to evaluate the independent, joint, and interactive effects of ABI and baPWV on the risk of all-cause and expanded CVD mortality. A total of 474 patient deaths occurred after a mean follow-up of 8.4 years, and 268 of which were attributed to cardiovascular events. Abnormal ABI (≤ 0.9) and highest baPWV quartile were independently associated with increased risks of all-cause ABI hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.30-2.11 baPWV 1.63, 1.16-2.27 and expanded CVD mortality (ABI 2.21, 1.62-3.02 baPWV 1.75, 1.09-2.83). The combination of abnormal ABI (≤ 0.9) and highest baPWV quartile was associated with a significantly higher risk of all-cause (4.51, 2.50-8.11) and expanded CVD mortality (9.74, 4.21-22.51) compared with that of the combination of normal ABI and lowest baPWV quartile. Significant interactions were observed between ABI and baPWV in relation to all-cause and expand CVD mortality (both p for interaction < 0.001). Through their independent, joint, and interactive effects, ABI and baPWV are significant parameters that can improve the prediction of all-cause and expanded CVD mortality in patients with T2DM and help identify high-risk patients who may benefit from diabetes care.

Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots.

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VATASAT, VATGFAT, and ASATGFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results - using MRI-derived, BMI-independent measures of local adiposity - confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

The predictive value of Thromboelastography (TEG) parameters in vascular complications in patients with type 2 diabetes mellitus.

The purpose of this research was to explore the association of TEG parameters (Reaction time, R Clot kinetics, K Alpha angle, α-angle Maximum amplitude, MA) with vascular complications of type 2 diabetes mellitus (T2DM), and assess whether TEG parameters could predict T2DM patients with vascular complications. A total of 68 healthy controls (HC), 57 T2DM patients without vascular complications (NC), 18 T2DM patients with only microvascular complications (MIC), 196 T2DM patients with only macrovascular complications (MAC), and 94 T2DM patients with both microvascular and macrovascular complications (MICMAC) were recruited in this study. Participants clinical information and TEG parameters were recorded. TEG parameters were analyzed by the Jonckheere-Terpstra trend test, assuming the vascular complication was progressing from HC → NC → MIC → MICMAC or HC → NC → MAC → MICMAC. Receiver operating characteristic (ROC) was performed to explore the diagnostic accuracy of TEG parameters in T2DM with vascular complications. Shorter TEGK, higher TEG-α-angle, and higher TEG-MA were found in T2DM patients with both microvascular and macrovascular complications (MICMAC) group compared with healthy controls (HC) group and T2DM patients without vascular complications (NC) group (P < 0.05). Trend analysis showed that TEG-RK decreased, but TEG-α-angleMA increased gradually as the vascular complication progressed (P < 0.001). With stratification of urine microalbumincreatinine ratio (UACR), diabetic nephropathy with macroalbuminuria (grade A3) behaves shorter TEGK, higher TEG-α-angleMA compared with normal to mildly increased albuminuria (grade A1) and microalbuminuria (grade A2) (P < 0.05). ROC curves implied that TEGK, TEG-α-angle, and TEG-MA have moderate diagnostic values in T2DM without vascular complications (K-AUC 0.780, α-angle-AUC 0.773, and MA-AUC 0.740) as well as T2DM with both microvascular and macrovascular complications (K-AUC 0.778, α-angle-AUC 0.757, and MA-AUC 0.800). TEG parameters are associated with the progression of vascular complications in T2DM, and it could be a diagnostic indicator for T2DM without vascular complications or with advanced vascular complications.

Glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy in type 2 diabetes.

Type 2 diabetes (T2D) is a national health priority. Its rising prevalence is accompanied by a high burden of diabetes-related complications, many of which are preventable. Numerous glucose-lowering medications have been developed in recent years with growing evidence relating to their efficacy and safety. These advances have increased the complexity of prescribing decisions in T2D. This review provides clinicians with relevant evidence and practical advice concerning glucagon-like peptide-1 receptor agonists (GLP1-RAs) in T2D. The Royal Australian College of General Practitioners recommends GLP1-RAs as an option for second-line therapy in T2D. GLP1-RAs contribute to weight loss and glycated haemoglobin reduction. GLP1-RAs also reduce incidence of cardiovascular events in selected populations, and available evidence suggests renoprotective effects. Common adverse effects include gastrointestinal symptoms, especially in the weeks following treatment initiation. GLP1-RAs should be considered for people with T2D at high cardiovascular risk or where weight loss is a priority.

The impact of a prolonged lockdown and utilization of diabetes telemedicine on cardiometabolic health in people with diabetes during the COVID-19 outbreak in Saudi Arabia.

To mitigate the spread of COVID-19, Saudi Arabia implemented a nationwide lockdown that lasted for approximately five months. Due to the limited availability of telemedicine in Saudi Arabia, many people with diabetes (PWD) lost access to diabetes care services during the lockdown period. Here, we examined the impact of lockdown on cardiometabolic health in PWD and how this may have differed between those who utilized diabetes telemedicine during lockdown versus those who did not. Hemoglobin A1C (A1C), body weight, lipid, and other cardiometabolic parameters were retrospectively reviewed in 384 PWD who attended routine clinic visits in the pre-lockdown (September 2019 to March 2020) and post-lockdown (Aug to Dec 2020) periods. Changes in cardiometabolic parameters from pre- to post-lockdown were compared across 3 groups according to the type of visit that they had during lockdown (April to July 2020) no visit (n 215), in-person visit (n 44), or virtual visit (n 125). The virtual visits in our institution followed a simplified protocol that utilized technological tools readily available to most PWD and clinicians. PWD who attended virtual visits during lockdown were the youngest and most likely to have type 1 diabetes followed by those who attended in-person visits and those who had no visit. A significant reduction in A1C from pre- to post-lockdown periods was noted in PWD who attended a virtual visit (9.02 to 8.27%, respectively, p lt 0.01) and those who attended an in-person visit (9.18 to 8.43%, respectively, p lt 0.05) but not in those who had no visit (8.75 to 8.57%, p gt 0.05). No significant changes were noted in serum glucose, blood pressure, or lipid parameters during the lockdown in any of the groups. Simplified telemedicine visits, including real-time audio calls, were as effective as in-person visits in improving glycemic control in PWD during the lockdown period in a country where telemedicine infrastructure was not well-established. Older adults and those with type 2 diabetes were less likely to utilize telemedicine suggesting a potential risk of digital divide that warrants greater attention in the future.

Prediction models of diabetes complications a scoping review.

Diabetes often places a large burden on people with diabetes (hereafter patients) and the society, that is, in part attributable to its complications. However, evidence from models predicting diabetes complications in patients remains unclear. With the collaboration of patient partners, we aimed to describe existing prediction models of physical and mental health complications of diabetes. Building on existing frameworks, we systematically searched for studies in Ovid-Medline and Embase. We included studies describing prognostic prediction models that used data from patients with pre-diabetes or any type of diabetes, published between 2000 and 2020. Independent reviewers screened articles, extracted data and narratively synthesised findings using established reporting standards. Overall, 78 studies reported 260 risk prediction models of cardiovascular complications (n42 studies), mortality (n16), kidney complications (n14), eye complications (n10), hypoglycaemia (n8), nerve complications (n3), cancer (n2), fracture (n2) and dementia (n1). Prevalent complications deemed important by patients such as amputation and mental health were poorly or not at all represented. Studies primarily analysed data from older people with type 2 diabetes (n54), with little focus on pre-diabetes (n0), type 1 diabetes (n8), younger (n1) and racialised people (n10). Per complication, predictors vary substantially between models. Studies with details of calibration and discrimination mostly exhibited good model performance. This rigorous knowledge synthesis provides evidence of gaps in the landscape of diabetes complication prediction models. Future studies should address unmet needs for analyses of complications n> and among patient groups currently under-represented in the literature and should consistently report relevant statistics. SCOPING REVIEW REGISTRATION httpsosf.iofjubt.

Automated analysis of corneal nerve tortuosity in diabetes implications for neuropathy detection.

There is potential benefit in analysing corneal nerve tortuosity as a marker for assessment and progression of systemic diabetic neuropathy. The aim of this work was to determine whether tortuosity significantly differs in participants with type 1 (T1DM) and type 2 (T2DM) diabetes compared to controls and whether tortuosity differed according to neuropathy status. Corneal nerves of 164 participants were assessed across T1DM, T2DM and control groups. Images of corneal nerves were captured via in vivo corneal confocal microscopy. Diabetic neuropathy status was examined using the Total Neuropathy Score (TNS). Tortuosity was assessed with Cfibre v0.097. Results were compared between groups with a linear mixed model accounting for location of image and controlling for age, producing Tortuosity Factor (TF), an estimate of the marginal means of each group. Tortuosity was significantly reduced in the T1DM group compared to controls (TF 0.241, 95%CI 0.225-0.257 vs. TF 0.272, 95%CI 0.252-0.292 mean difference -0.031, p 0.02) and in the T2DM group compared to controls (TF 0.261, 95%CI 0.244-0.278 vs. TF 0.289, 95%CI 0.270-0.308 mean difference -0.029, p 0.03). Tortuosity did not significantly differ between participants with T1DM and T2DM accounting for age and TNS (TF 0.240, 95%CI 0.215-0.265 vs. 0.269, 95%CI 0.244-0.293, mean difference -0.029, p 0.11). Tortuosity was significantly reduced in participants with neuropathy (TNS≥2) compared to participants with no neuropathy (TNS< 2) (TF 0.248, 95%CI 0.231-0.265 vs. TF 0.272, 95%CI 0.260-0.283 mean difference -0.024, p 0.03). Tortuosity is significantly reduced in participants with T1DM and T2DM compared to age matched controls and in participants with neuropathy compared to those without neuropathy.

Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure.

The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization. The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk. Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mgday. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pgmL), were randomized to atrasentan 0.75 mgday or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations. Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR 1.39 95% CI 0.97-1.99 P 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR 2.32 95% CI 1.81-2.97) and percent increase in BNP during response enrichment (HR 1.46 95% CI 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR 1.02 95% CI 0.66-1.56) while retaining nephroprotective effects (HR 0.58 95% CI 0.44-0.78). In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan SONAR NCT01858532).

Multimodal imaging analysis for the impact of retinal peripheral lesions on central neurovascular structure and retinal function in type 2 diabetes with diabetic retinopathy.

To explore the possible role of peripheral lesions (PLs) detected by ultrawide field (UWF) imaging system on central neurovascular structure and retinal function. Ninety-seven diabetic patients were included in this cross-sectional study using UWF pseudocolour colour imaging with Optos Daytona (Optos, PLC). UWF images were graded as with predominantly peripheral lesions (PPLs) and without PPL. Macular neurovascular alterations and retinal function were measured by optical coherence tomography angiography (OCTA) and RETeval device, respectively. Central microcirculation and retinal function were compared between eyes with and without PPL. The study evaluated 186 eyes (97 patients 43 females (44.3%)), including 92 eyes without PPL and 94 eyes with PPL. Central retinal vessel density was comparable between eyes with and without PPL. Delayed implicit time and decreased pupil area ratio were found in the PPL group compared with eyes without PPL, and this difference remained unchanged after adjusting for systemic factors (all p＜0.01). Our study suggests that retinal function is worse in diabetic eyes with PPL. These findings challenged the conventional ETDRS protocols which ignored peripheral retina in determining DR severity. Furthermore, combining UWF imaging with RETeval system to detect more retinal abnormalities may be helpful in DR management.

One-hour post-load glucose is associated with severity of hepatic fibrosis risk.

Individuals with high 1-hour post-load glucose (1-h PG > 155 mgdl 8.6 mmoll) during an oral glucose tolerance test are at increased risk of type 2 diabetes (T2D) and cardiovascular complications, hepatic steatosis, and mortality. However,the clinical relevance of 1-h PG for the severity of hepatic fibrosis risk remains undefined. Cross-sectional data of the CATAMERI study (n 2335) were analyzed. Participants underwent anthropometric measurements, liver enzyme determinations, cardiometabolic profiling, and a75-gram oral glucose tolerance test, including fasting, 1-h and 2-h PG determinations and measurement of FIB-4 score to assess degree of hepatic fibrosis. Multivariable logistic regression analysis was performed to evaluate risk of advanced hepatic fibrosis with worsening glycemic status. We stratifiedthe study group into 6 categories based on glycemic status normal glucose tolerance (NGT) 1h-PG Low, NGT 1h-PG High, iIFG 1h-PG Low, iIFG 1h-PG High, IGT, and newly detected T2D. Anthropometric and cardiometabolic profiles worsened gradually with glycemic status. Moreover, compared to NGT-1h-PG Low group, worsening glycemic status was significantly associated with the severity of fibrosis, independent of other significant clinical risk factors. 1-PG is a valuable tool for stratifying subjects with NGT or IFG at heightened risk of hepatic fibrosis requiring further evaluation with elastography.

Cardiodiabetology newer pharmacologic strategies for reducing cardiovascular disease risks.

Globally, nearly 500 million adults currently have diabetes, which is expected to increase to approximately 700 million by 2040. Cardiovascular diseases (CVD), including coronary heart disease, stroke, heart failure, and peripheral arterial disease, are the principal causes of death in persons with diabetes. Key to the prevention of CVD is optimization of associated risk factors. However, few persons with diabetes are at recommended targets for key CVD risk factors including low-density lipoprotein-cholesterol (LDL-C), blood pressure, glycated hemoglobin, nonsmoking status, and body mass index. While lifestyle management forms the basis for the prevention and control of these risk factors, newer and existing pharmacologic approaches are available to optimize the potential for CVD risk reduction, particularly for the management of lipids, blood pressure, and blood glucose. For higher-risk patients, antiplatelet therapy is recommended. Medication for blood pressure, statins, and most recently, icosapent ethyl, have evidence for reducing CVD events in persons with diabetes. Newer medications for diabetes, including sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists, also reduce CVD and SGLT2 inhibitors in particular also reduce progression of kidney disease and reduce heart failure hospitalizations (HFHs). Most importantly, a multidisciplinary team is required to address the polypharmaceutical options to best reduce CVD risks persons with diabetes.

Vitamin D status, genetic factors, and risk of cardiovascular disease among individuals with type 2 diabetes a prospective study.

The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when vitamin D concentration was below a particular threshold. To investigate the associations of serum 25-hydroxyvitamin D 25(OH)D concentrations and genetic factors with risks of total and subtypes of CVD in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. This prospective study included 15,103 individuals with T2D, initially free of CVD and with serum 25(OH)D measurements in UK Biobank. Incidence of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke, respectively. The mean (standard deviation) of serum 25(OH)D concentration was 43.4 (20.4) nmolL, and 65.7% participants had vitamin D below 50 nmolL. During a median of 11.2 years of follow-up, 3,534 incident CVD events were documented. Compared with individuals with 25(OH)D <25 nmolL, participants with 25(OH)D ≥75 nmolL had an HR of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D ≥50 nmolL and low GRS, as compared with individuals with 25(OH)D <25 nmolL and high GRS, had a 50% (39%, 65%) lower risk of IHD. No significant interactions between serum 25(OH)D and the GRSs and genetic variants in vitamin D receptor (VDR) were demonstrated. Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of genetic susceptibility and genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmolL. These findings suggest that maintaining adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D.

Heterogeneous Development of β-Cell Populations in Diabetes-Resistant and -Susceptible Mice.

Progressive dysfunction and failure of insulin-releasing β-cells are a hallmark of type 2 diabetes (T2D). To study mechanisms of β-cell loss in T2D, we performed islet single-cell RNA sequencing of two obese mouse strains differing in their diabetes susceptibility. With mice on a control diet, we identified six β-cell clusters with similar abundance in both strains. However, after feeding of a diabetogenic diet for 2 days, β-cell cluster composition markedly differed between strains. Islets of diabetes-resistant mice developed into a protective β-cell cluster (Beta4), whereas those of diabetes-prone mice progressed toward stress-related clusters with a strikingly different expression pattern. Interestingly, the protective cluster showed indications of reduced β-cell identity, such as downregulation of GLUT2, GLP1R, and MafA, and in vitro knockdown of GLUT2 in β-cells-mimicking its phenotype-decreased stress response and apoptosis. This might explain enhanced β-cell survival of diabetes-resistant islets. In contrast, β-cells of diabetes-prone mice responded with expression changes indicating metabolic pressure and endoplasmic reticulum stress, presumably leading to later β-cell loss. In conclusion, failure of diabetes-prone mice to adapt gene expression toward a more dedifferentiated state in response to rising blood glucose levels leads to β-cell failure and diabetes development.

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes.

Tea polysaccharide (TPS) is a bioactive compound that has attracted increasing attention for its health effect on regulating the metabolism of glucose and lipid. Moreover, due to their good biocompatibility and biodegradability, TPS-based nanoparticles have emerged as effective nanocarriers for the delivery of bioactive molecules. In this study, we developed a TPS-based biocarrier system for the orally targeted administration of Mn(II) ions and investigated their antidiabetic effects in C57BL6 mice with HFDstreptozotocin (STZ)-induced T2DM. Mn(II)-loaded TPS-based nanoparticles (MTNPs) were synthesized, in which negatively charged functional groups in protein and uronic acid in TPS conjugates would act as binding sites for Mn(II) ions, which is responsible for the cross-linking reaction of MTNP. The resulting MTNP had a spherical shape and a mean particle size of around 30 nm with a Mn(II) ion content of 2.24 ± 0.13 mgg. In T2DM mice, we discovered that MTNP treatment significantly lowered blood glucose levels and improved glucose intolerance. Furthermore, the impact of MTNP on the recovery of FINS, the homeostatic index of insulin resistance (HOMA-IR), and the homeostatic index of β-cell (HOMA β-cell) levels was significantly larger (

The many facets of CD26dipeptidyl peptidase 4 and its inhibitors in disorders of the CNS - a critical overview.

Dipeptidyl peptidase 4 is a serine protease that cleaves X-proline or X-alanine in the penultimate position. Natural substrates of the enzyme are glucagon-like peptide-1, glucagon inhibiting peptide, glucagon, neuropeptide Y, secretin, substance P, pituitary adenylate cyclase-activating polypeptide, endorphins, endomorphins, brain natriuretic peptide, beta-melanocyte stimulating hormone and amyloid peptides as well as some cytokines and chemokines. The enzyme is involved in the maintenance of blood glucose homeostasis and regulation of the immune system. It is expressed in many organs including the brain. DPP4 activity may be effectively depressed by DPP4 inhibitors. Apart from enzyme activity, DPP4 acts as a cell surface (co)receptor, associates with adeosine deaminase, interacts with extracellular matrix, and controls cell migration and differentiation. This review aims at revealing the impact of DPP4 and DPP4 inhibitors for several brain diseases (virus infections affecting the brain, tumours of the CNS, neurological and psychiatric disorders). Special emphasis is given to a possible involvement of DPP4 expressed in the brain.While prominent contributions of extracerebral DPP4 are evident for a majority of diseases discussed herein a possible role of brain DPP4 is restricted to brain cancers and Alzheimer disease. For a number of diseases (Covid-19 infection, type 2 diabetes, Alzheimer disease, vascular dementia, Parkinson disease, Huntington disease, multiple sclerosis, stroke, and epilepsy), use of DPP4 inhibitors has been shown to have a disease-mitigating effect. However, these beneficial effects should mostly be attributed to the depression of peripheral DPP4, since currently used DPP4 inhibitors are not able to pass through the intact blood-brain barrier.

Household Food Insecurity and Fear of Hypoglycemia in Adolescents and Young Adults With Diabetes and Parents of Youth With Diabetes.

To evaluate the relation between household food insecurity (HFI) and fear of hypoglycemia among young adults with type 1 and type 2 diabetes and adolescents with type 1 diabetes and their parents. We analyzed cross-sectional data of 1,676 young adults with youth-onset diabetes (84% type 1, 16% type 2) and 568 adolescents (<18 years old mean age 15.1 years) with type 1 diabetes from the SEARCH for Diabetes in Youth study. Adult participants and parents of adolescent participants completed the U.S. Household Food Security Survey Module. Adults, adolescents, and parents of adolescents completed the Hypoglycemia Fear Survey, where answers range from 1 to 4. The outcomes were mean score for fear of hypoglycemia and the behavior and worry subscale scores. Linear regression models identified associations between HFI and fear of hypoglycemia scores. Adults with type 1 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.22 units higher for behavior, 0.55 units for worry, 0.40 units for total all P < 0.0001) than those without HFI. No differences by HFI status were found for adolescents with type 1 diabetes. Parents of adolescents reporting HFI had a 0.18 unit higher worry score than those not reporting HFI (P < 0.05). Adults with type 2 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.19 units higher for behavior, 0.35 units for worry, 0.28 units for total all P < 0.05) than those in food secure households. Screening for HFI and fear of hypoglycemia among people with diabetes can help providers tailor diabetes education for those who have HFI and therefore fear hypoglycemia.

Measures of Insulin Resistance as a Screening Tool for Dysglycemia in Patients With Coronary Artery Disease A Report From the EUROASPIRE V Population.

The optimal screening strategy for dysglycemia (including type 2 diabetes and impaired glucose tolerance) in patients with coronary artery disease (CAD) is debated. We tested the hypothesis that measures of insulin resistance by HOMA indexes may constitute good screening methods. Insulin, C-peptide, glycated hemoglobin A1c, and an oral glucose tolerance test (OGTT) were centrally assessed in 3,534 patients with CAD without known dysglycemia from the fifth European Survey of Cardiovascular Disease Prevention and Diabetes (EUROASPIRE V). Three different HOMA indexes were calculated HOMA of insulin resistance (HOMA-IR), HOMA2 based on insulin (HOMA2-ins), and HOMA2 based on C-peptide (HOMA2-Cpep). Dysglycemia was diagnosed based on the 2-h postload glucose value obtained from the OGTT. Information on study participants was obtained by standardized interviews. The optimal thresholds of the three HOMA indexes for dysglycemia diagnosis were obtained by the maximum value of Youdens J statistic on receiver operator characteristic curves. Their correlation with clinical parameters was assessed by Spearman coefficients. Of 3,534 patients with CAD (mean age 63 years 25% women), 41% had dysglycemia. Mean insulin, C-peptide, and HOMA indexes were significantly higher in patients with versus without newly detected dysglycemia (all P < 0.0001). Sensitivity and specificity of the three HOMA indexes for the diagnosis of dysglycemia were low, but their correlation with BMI and waist circumference was strong. Screening for dysglycemia in patients with CAD by HOMA-IR, HOMA2-ins, and HOMA2-Cpep had insufficient diagnostic performance to detect dysglycemia with reference to the yield of an OGTT, which should still be prioritized despite its practical drawbacks.

Does the Structure Matter An External Validation and Health Economic Results Comparison of Event Simulation Approaches in Severe Obesity.

As obesity-associated events impact long-term survival, health economic (HE) modelling is commonly applied, but modelling approaches are diverse. This research aimed to compare the events simulation and the HE outcomes produced by different obesity modelling approaches. An external validation, using the Swedish obesity subjects (SOS) study, of three main structural event modelling approaches was performed (1) continuous body mass index (BMI) approach (2) risk equation approach and (3) categorical BMI-related approach. Outcomes evaluated were mortality, cardiovascular events, and type 2 diabetes (T2D) for both the surgery and the control arms. Concordance between modelling results and the SOS study were investigated by different state-of-the-art measurements, and categorized by the grade of deviation observed (grades 1-4 expressing mild, moderate, severe, and very severe deviations). Furthermore, the costs per quality-adjusted life-year (QALY) gained of surgery versus controls were compared. Overall and by study arm, the risk equation approach presented the lowest average grade of deviation (overall grade 2.50 control arm 2.25 surgery arm 2.75), followed by the continuous BMI approach (overall 3.25 control 3.50 surgery 3.00) and by the categorial BMI approach (overall 3.63 control 3.50 surgery 3.75). Considering different confidence interval limits, the costs per QALY gained were fairly comparable between all structural approaches (ranging from £2,055 to £6,206 simulating a lifetime horizon). None of the structural approaches provided perfect external event validation, although the risk equation approach showed the lowest overall deviations. The economic outcomes resulting from the three approaches were fairly comparable.

A genome-wide cross-trait analysis identifies shared loci and causal relationships of type 2 diabetes and glycaemic traits with polycystic ovary syndrome.

The link underlying abnormal glucose metabolism, type 2 diabetes and polycystic ovary syndrome (PCOS) that is independent of BMI remains unclear in observational studies. We aimed to clarify this association using a genome-wide cross-trait approach. Summary statistics from the hitherto largest genome-wide association studies conducted for type 2 diabetes, type 2 diabetes mellitus adjusted for BMI (T2DM A positive overall genetic correlation between type 2 diabetes and PCOS was observed, largely influenced by BMI (r We found a genetic link underlying type 2 diabetes, glycaemic traits and PCOS, driven by both biological pleiotropy and causal mediation, some of which is independent of BMI. Our findings highlight the importance of controlling fasting insulin levels to mitigate the risk of PCOS, as well as screening for and long-term monitoring of type 2 diabetes in all women with PCOS, irrespective of BMI.

Patterns of Timing and Intensity of Physical Activity and HbA

Despite the clear benefits of increased physical activity (PA) on glycemic control, little is known about the importance of the timing of exercise among people with diabetes. Our objective was to compare the time of day of PA with concurrent HbA

Remote Research Resources, Intervention Needs, and Methods in People with Diabetes and Peripheral Neuropathy.

Stay-at-home orders associated with the SARS-CoV-2 (COVID-19) pandemic were particularly important for older adults with type 2 diabetes, at risk for severe COVID-19 complications. In response, research shifted to remote telehealth methodology. Study participant interests, equipment needs, and ability to adapt methods to the remotetelehealth environment were unknown. Study purposes to assess (1) resource needs (internetdevices accessibility), (2) future telehealth interests, and (3) ability to adapt common research and clinical measures of glycemic control, physical function, activity measures, and quality of life outcomes to a telehealth setting. Twenty-one participants with type 2 diabetes and peripheral neuropathy were recruited from a longitudinal study (11 female age 66.3 ± 8.3 years DM 15.1 ± 8.7 years). Technology needs and future telehealth interests were assessed. A glycemic measure (HbA1c), a five-times chair rise, a one-week activity monitor, and surveys (self-efficacy, depression, and balance) were collected. All aspects of the study were completed remotely over email and videophone call. Twelve participants used computers nine used phones for study completion. Participants had the following resource needs connectivity (n 3), devices (n 6), and technical support (n 12). Twenty people expressed interest in participating in future telehealth studies related to balance, exercise, and diabetes management. Methodological considerations were primarily the need for assistance for participants to complete the home HbA1c test, five-time chair rise, wearable activity monitoring, and surveys. Older adults with type 2 diabetes and peripheral neuropathy would need technological and personal assistance (connection, device, guidance) to complete a long-term telehealth intervention. Despite technology needs, participants were interested in telehealth interventions. Parent study, Metatarsal Phalangeal Joint Deformity Progression-R01 (NCT02616263) is registered at httpsclinicaltrials.gov.

Chemerin Levels in Acute Coronary Syndrome Systematic Review and Meta-Analysis.

We evaluated the relevant published studies exploring the association between chemerin concentrations and acute coronary syndromes (ACSs). A systematic search was performed in October 2021 using PubMed, Scopus, Embase, and Cochrane Library. We included full articles and assessed their quality using the Newcastle-Ottawa score. We found 6 studies in the systematic review and 5 of these were included in our meta-analysis. Mean difference (MD) of 41.69 ngmL (95% CI, 10.07-73.30), 132.14 ngmL (95% CI, -102.12-366.40), and 62.10 ngmL (95% CI, 10.31-113.89) in chemerin levels was seen in ACS patients vs control subjects, ACS patients vs stable angina pectoris patients (SAP), and type 2 diabetes mellitus (T2DM) ACS patients vs nondiabetic ACS patients, respectively. Chemerin levels were significantly elevated in patients with ACS compared to controls, as well as in T2DM-ACS patients compared to nondiabetic ACS patients. However, no significant MD in chemerin levels was observed between SAP and ACS patients.

Mutations in GCK May Lead to MODY2 by Reducing Glycogen Synthesis.

Dysfunction of glucokinase (GCK) caused by mutations in the GCK gene is the main cause of maturity-onset diabetes of the young type-2 (MODY2, also known as GCK-MODY), which is usually present in adolescence or young adulthood. MODY2 is characterized by mild, stable fasting hyperglycemia that presents at birth, usually 5.4-8.3 mmol L

The Leaves of

Type 2 diabetes mellitus (T2DM) has become a universal and chronic global public health concern and causes multiple complex complications. In order to meet the rapidly growing demand for T2DM treatment, increased research has been focused on hypoglycemic drugs.

Short-Term Intraocular Pressure Response to the Combined Effect of Transcutaneous Electrical Nerve Stimulation over Acupoint (Acu-TENS) and Yoga Ocular Exercise in Type 2 Diabetic Patients with Primary Open-Angle Glaucoma A Randomized Controlled trial.

Despite the adherence to medications, the control of the modifiable key risk factor-intraocular pressure (IOP)-for the progression of primary open-angle glaucoma (POAG) in diabetics is usually difficult hence, many glaucoma patients try other alternative therapeutic options. Objectives This randomized controlled study investigated the short-term IOP response to the combined effects of transcutaneous electrical nerve stimulation over acupoint (Acu-TENS) and yoga ocular exercise in type 2 diabetics with POAG. Eighty diabetics with bilateral POAG, ages ≥ 50 years, IOP > 21 mmHg in both eyes, and a body mass index below 30 kgm The repeated measures analysis of variance revealed a greater significant decline of IOP in group A than group B in both eyes at the consecutive intervals of time measurements. According to this short-term observation, the addition of Acu-TENS to yoga ocular exercise could reduce the high IOP in diabetic patients with POAG, but further longterm trials are needed.

Metformin improves the weight reduction effect of mazindol in prediabetic obese Mexican subjects.

Obesity is the strongest risk factor for type 2 diabetes (T2D). We aimed to explore 7% weight reduction rates of mazindol alone or combined with metformin in non-diabetic obese Mexican subjects who had additional risk factors for T2D. In this randomized double-blind study, 137 participants received 1 mg mazindol (n 65) alone or combined with 500 mg metformin (n 72), twice a day, for 6 months. Mazindol and mazindol-metformin were similarly effective. However, when subjects were subclassified into non-diabetics and prediabetics, according to glycated hemoglobin (HbA1c) - < 5.7% and 5.7 - 6.4%, respectively - andor fasting plasma glucose (FPG) - < 100 mgdL and 100 - 125 mgdL, respectively -, differences were evident. Prediabetics in the mazindol-metformin group had a higher rate of 7% weight reduction (78.4%, n 37) compared to prediabetics treated with mazindol (48.3%, n 29). Furthermore, mazindol-metformin treatment induced significant reductions in fasting plasma insulin, HOMA-IR, and HbA1c in prediabetics compared to mazindol. No differences were found in any parameter between non-diabetics treated with mazindol (n 36) and mazindol-metformin (n 35). Our results highlight the effectiveness of mazindol-metformin to achieve higher rates of 7% weight reduction and to improve the glycemic profile in prediabetic obese subjects, which could be useful to prevent or delay T2D in these subjects.

The Effects of Different Types of Exercise on Circulating Irisin Levels in Healthy Individuals and in People With Overweight, Metabolic Syndrome and Type 2 Diabetes.

Irisin is a myokine secreted during exercise. It has drawn the attention of researchers as it regulates several effects of exercise that are considered beneficial. It has also been proposed as a therapeutic tool to treat metabolic disorders. In recent years, the effect of different types of training on circulating irisin has been studied in large populations. An overall beneficial result has been shown, however, the outcome of the investigations has raised some controversy. Herein we evaluated the existing literature on the effects of different types of training on the circulating irisin levels in healthy subjects and in those displaying different metabolic condition. We conducted queries in the PubMed and Web of Science databases for literature published between January 2010 and January 2021. Thirty-seven original articles were retrieved and they were included in this review. Any letter to the editor, meta-analyses, reviews, and systematic review articles were excluded. From these 37 articles, 19 of them reported increased levels of circulating irisin. The interventions encompassed aerobic, resistance, combined, circuit, and interval training types. Such increase of circulating irisin was reported for healthy subjects and for those displaying different metabolic condition. A training that is steadily kept with a moderate to high intensity, including that characterized by brief highly intense intervals, were distinguishable from the rest. Nevertheless, the training effectiveness as evaluated by the increased circulating irisin levels depends on the subjects metabolic condition and age.

Obesity Fact Sheet in Korea, 2021 Trends in Obesity Prevalence and Obesity-Related Comorbidity Incidence Stratified by Age from 2009 to 2019.

The global public health burden of obesity has increased with socio-economic development. The Korean Society for the Study of Obesity released the 2021 Obesity Fact Sheet to address trends in obesity prevalence and comorbid conditions by different age groups. Individuals ≥20 years old who underwent a health checkup provided by the Korean National Health Insurance Service between 2009 and 2019 were included. The prevalence of obesity and abdominal obesity was standardized by age and sex based on the 2010 population and housing census. The incidence of obesity-related comorbidities was tracked from 2009 to 2019, and the incidence per 1,000 person-years was calculated using Poisson regression adjusted for age and sex. Obesity and abdominal obesity prevalence has increased for the entire population over the past 11 years. Obesity prevalence has risen rapidly in individuals in their 20s and 80s compared with other age groups. Additionally, class III obesity prevalence in both men and women has significantly increased by nearly threefold. The relative risk of developing type 2 diabetes, myocardial infarction, ischemic stroke, and cancers in people with obesity or abdominal obesity is greater than in people without obesity or abdominal obesity. The relative risk was higher in young and middle-aged individuals than in the older population. The findings based on the 2021 Obesity Fact Sheet suggest the need to better understand obesity characteristics according to age and sex and to establish individualized treatment strategies.

The association of specific types of vegetables consumption with 10-year type II diabetes risk Findings from the ATTICA cohort study.

The present study aimed to investigate the association between vegetable consumption, in total as well as per typecategory, and 10-year type-2 diabetes mellitus (T2DM) incidence. The ATTICA study was conducted during 2001-2012 in 3042 apparently healthy adults living in Athens area, Greece. A detailed biochemical, clinical, and lifestyle evaluation was performed vegetable consumption (total, per type) was evaluated through a validated semi-quantitative food frequency questionnaire. After excluding those with no complete information of diabetes status or those lost at the 10-year follow-up, data from 1485 participants were used for the current analysis. After adjusting for several participants characteristics, including overall dietary habits, it was observed that participants consuming at least 4 servingsday of vegetables had a 0.42-times lower risk of developing T2DM (hazard ratio HR 0.42 95% confidence interval CI 0.29-0.61) the benefits of consumption were greater in women (HR 0.29 95% CI 0.16-0.53) compared to men (HR 0.56 95% CI 0.34-0.92). Only 33% of the sample consumed vegetables 4 servingsday. The most significant associations were observed for allium vegetables in women and for redorangeyellow vegetables, as well as for legumes in men. The intake of at least 4 servingsday of vegetables was associated with a considerably reduced risk of T2DM, independently of other dietary habits underlying the need for further elaboration of current dietary recommendations at the population level.

Exercise and Metabolic Health The Emerging Roles of Novel Exerkines.

Physical inactivity is a major cause of chronic diseases. It shortens the health span by lowering the age of the first chronic disease onset, which leads to decreased quality of life and increased mortality risk. On the other hand, physical exercise is considered a miracle cure in the primary prevention of at least 35 chronic diseases, including obesity, insulin resistance, and type 2 diabetes. However, despite many scientific attempts to unveil the health benefits conferred by regular exercise, the underlying molecular mechanisms driving such benefits are not fully explored. Recent research shows that exercise-induced bioactive molecules, named exerkines, might play a critical role in the regulation of metabolic homeostasis and thus prevent metabolic diseases. Here we summarize the current understanding of the health-promoting effects of exerkines secreted from skeletal muscle, adipose tissue, bone, and liver, including MOTS-c, BDNF, miR-1, 12,13-diHOME, irisin, SPX, OC, GDF15, and FGF21 on obesity, insulin resistance, and type 2 diabetes. Identifying the systemic health benefits of exerkines may open a new area for the discovery of new pharmacological strategies for the prevention and management of metabolic diseases.

Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort.

Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degenerationfailure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell-produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin-like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes. To characterize insulin-like peptide 3 as a biomarker to assess gonadal status in aging men. A large European multicenter (European Male Aging Study) cohort of community-dwelling men was analyzed to determine how insulin-like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters. Insulin-like peptide 3 declines cross-sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin-like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin-like peptide 3 is negatively dependent on luteinizing hormone and sex hormone-binding globulin and positively dependent on follicle-stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin-like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin-like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European-wide reference range for insulin-like peptide 3 (95% confidence interval) adjusted for increasing age. Insulin-like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin-dependent short-term regulation and within-individual variation in testosterone.

Pancreatitis, pregestational diabetes and hyperchylomicronia in a pregnant woman with COVID-19.

A 37-year-old pregnant woman, was diagnosed with acute pancreatitis whilst being infected with COVID-19. Additionally, she had a hyperchylomicronemia and an uncontrolled (most probably, pre-gestational) type 2 diabetes. The coronavirus is able to enter the pancreatic cells through ACE-2 receptors. On the pancreatic level, ACE- 2 receptor expression is present but not as abundant as on pulmonary level. However, with inflammation (due to hyperchylomicronemia), the ACE-2 receptor expression may change and hypothetically make the pancreas more susceptible for a Covid-19 surinfection. Here it is difficult to conclude whether the COVID-19 infection contributed substantially to the development of pancreatitis. Late term pregnancy, uncontrolled glycaemia and the heterozygote mutation in the GPIHBP1 gene (c.523G>C p Gly175Arg), all contribute to increased TG levels, a principal factor in the development of pancreatitis. This case shows a rare but serious clinical presentation late in pregnancy that could have interesting consequences postpartum.

Delving the Role of

Metabolic syndrome (MS), commonly known as syndrome X or insulin resistance syndrome, is a collection of risk factors for cardiovascular diseases and type II diabetes. MS is believed to impact over a billion individuals worldwide. It is a medical condition defined by visceral obesity, insulin resistance, high blood pressure, and abnormal cholesterol levels, according to the World Health Organization. The current dietary trends are more focused on the use of functional foods and nutraceuticals that are well known for their preventive and curative role against such pathological disorders.

Addressing Diabetes Distress in Self-Management Programs Results of a Randomized Feasibility Study.

West Virginia ranks 1st nationally in the prevalence of hypertension (HTN 43.8%) and diabetes (16.2%). Patients with type 2 diabetes mellitus (T2DM) are distressed over physical and psychological burden of disease self-management. This study investigated the effectiveness of an intervention to reduce diabetes distress and outcomes glycemic control, blood pressure (BP) among T2DM adults with comorbid HTN. Participants were randomized to a 12-week diabetes and hypertension self-management program versus a 3-month wait-listed control group. Trained health coaches and experts implemented the lifestyle program in a faith-based setting using an adapted evidence-based curriculum. Twenty adults with T2DM and HTN (n10 per group) completed baseline and 12-week assessments. Diabetes distress was measured by using a validated Diabetes Distress Survey (17-item Likert scale four sub-scales of emotional burden, physician related burden, regimen related burden, and interpersonal distress). Baseline and post-intervention changes in diabetes distress were compared for both groups reduction in distress in the intervention groups are depicted using waterfall plots. The mean age, HbA1c and BMI were 55 ± 9.6 years, 7.8 ± 2.24 and 36.4 ± 8.8, respectively. Diabetes distress (total mean) was 1.84±0.71. Participants reported higher diabetes distress related to emotional burden (2.1±0.94) and regimen-related distress (2.0 ± 0.74) physician-related distress was the lowest (1.18±0.64). In general, diabetes distress reduced among intervention participants and was especially significant among those with HbA1c ≤ 8% (r0.28, p0.4), and systolicdiastolic BP ≤14080 mm Hg (r0.045, P0.18). Findings suggest that lifestyle self-management programs have the potential to reduce diabetes distress.

Emphysematous liver abscess with

This report presents the case of a 51-year-old woman on an immunosuppressant drug and steroids, who presented with general fatigue and was admitted to the intensive care unit. Her serum procalcitonin, lactate, aspartate aminotransferase, and alanine aminotransferase levels and white blood cell counts were elevated. Computed tomography revealed gas formation in her liver, and her culture results revealed

The Transcultural Diabetes Nutrition Algorithm A Middle Eastern Version.

Diabetes prevalence is on the rise in the Middle East. In countries of the Gulf region-Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates-prevalence rates are among the highest in the world. Further, Egypt now ranks as one of the top 10 countries in the world for high number of people with diabetes. Medical nutrition therapy is key to optimal management of diabetes. Patient adherence to nutritional guidance depends on advice that is tailored to regional foods and cultural practices. In 2012, international experts created a transcultural Diabetes Nutrition Algorithm (tDNA) for broad applicability. The objective of this current project was to adapt the algorithm and supportive materials to the Middle East region. A Task Force of regional and global experts in the fields of diabetes, obesity, and metabolic disorders met to achieve consensus on Middle East-specific adaptations to the tDNA. Recommendations, position statements, figures, and tables are presented here, representing conclusions of the tDNA-Middle Eastern (tDNA-ME) Task Force. Educational materials can be used to help healthcare professionals optimize nutritional care for patients with type 2 diabetes. The tDNA-ME version provides evidence-based guidance on how to meet patients nutritional needs while following customs of people living in the Middle Eastern region.

Quantile Differences in the Age-Related Decline in Cardiorespiratory Fitness Between Sexes in Adults Without Type 2 Diabetes Mellitus in the United States.

To comprehensively assess the extent to which the decline in cardiorespiratory fitness (CRF) with age differs between sexes. This study used data from the Aerobics Center Longitudinal Study, conducted between September 1974 and August 2006, consisting primarily of White adults from middle-to-upper socioeconomic strata restricted to adults without type 2 diabetes mellitus (33,742 men and 9,415 women). Quantile regression models were used to estimate the differences in age-associated changes in CRF between the sexes, estimated using a maximal treadmill test. For adults aged up to 45 years, significant differences in slopes relating to age and CRF between men and women were observed for all adjusted percentiles of CRF other than the 90th percentile women reported significantly greater declines in CRF per year. For those aged 45-60 years and those older than 60 years, no significant differences in age-related declines in CRF were observed between the sexes. This study found that compared with men, the onset of decline in CRF was found to occur earlier and at lower CRF percentiles in women. This is of particular concern, given that compared with men, women already tend to have lower CRF levels. These findings suggest that maintaining the levels of physical activity sufficient to maintain moderate-to-high levels of fitness is particularly important for women earlier during adulthood.

Diabetes Mellitus Diagnosed in Childhood and Adolescence With Negative Autoimmunity Results of Genetic Investigation.

Monogenic diabetes is a rare form of diabetes, accounting for approximately 1% to 6% of pediatric diabetes patients. Some types of monogenic diabetes can be misdiagnosed as type 1 diabetes in children or adolescents because of similar clinical features. Identification of the correct etiology of diabetes is crucial for clinical, therapeutic, and prognostic issues. Our main objective was to determine the prevalence of monogenic diabetes in patients with diabetes mellitus, diagnosed in childhood or in adolescence, and negative autoimmunity. We retrospectively analyzed clinical data of 275 patients diagnosed with insulin-dependent diabetes at age <18yr in the last 10 years. 8.4% of subjects has negative autoimmunity. Their DNA was sequenced by NGS custom panel composed by 45 candidate genes involved in glucose metabolism disorder. Two novel heterozygous pathogenic or likely pathogenic variants (10,5% of autoantibody negative subjects) were detected the frameshift variant c.617618insA in NEUROD1 exon 2 and the missense change c.116T>C in INS exon 2. Our study corroborates previous results of other reports in literature. NGS assays are useful methods for a correct diagnosis of monogenic diabetes, even of rarest forms, highlighting mechanisms of pediatric diabetes pathogenesis.

Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.

Obesity and associated complications increasingly jeopardize global health and contribute to the rapidly rising prevalence of type 2 diabetes mellitus and obesity-related diseases. Developing novel methods for the prevention and treatment of excess body adipose tissue expansion can make a significant contribution to public health. Rho kinase is a Rho-associated coiled-coil-containing protein kinase (Rho kinase or ROCK). The ROCK family including ROCK1 and ROCK2 has recently emerged as a potential therapeutic target for the treatment of metabolic disorders. Up-regulated ROCK activity has been involved in the pathogenesis of all aspects of metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. The RhoAROCK-mediated actin cytoskeleton dynamics have been implicated in both white and beige adipogenesis. Studies using ROCK pan-inhibitors in animal models of obesity, diabetes, and associated complications have demonstrated beneficial outcomes. Studies

Association Between Serum Uric Acid Level and Carotid Atherosclerosis and Metabolic Syndrome in Patients With Type 2 Diabetes Mellitus.

Serum uric acid (SUA) is associated with many cardiovascular risk factors, such as metabolic syndrome (MetS) and subclinical atherosclerosis. However, the relationship of SUA with carotid atherosclerosis remains controversial. We aimed to investigate whether elevated SUA levels are associated with a high risk of carotid atherosclerosis and MetS in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study was performed with a sample of 1,947 hospitalized patients with T2DM. Carotid intima-media thickness and carotid artery plaques were measured Uric acid levels were negatively associated with HbA1C, eGFR, and HDL-C (all P < 0.001) and positively associated with WBC, BMI, ACR, creatinine, total cholesterol, triglycerides, LDL-C, systolic blood pressure, and diastolic blood pressure (all P < 0.001). After adjusting for multiple potential confounders, the risks were substantially higher for MetS in the highest quartile of SUA levels (odds ratio 2.91, 95% confidence interval 1.54-5.51, P 0.003 for trend) than in the lowest quartile of SUA levels. Furthermore, a significant increase was observed in the prevalence of overweightobesity, hypertension, and dyslipidemia across the SUA quartiles independent of confounders. However, no significant association was found between SUA quartile with the presence of carotid atherosclerosis. In patients with T2DM, SUA levels were closely associated with MetS and its components but not with carotid atherosclerosis.

The prevalence of comorbidities in Danish patients with obesity - A Danish register-based study based on data from 2002 to 2018.

We used the Danish National Health Registers to conduct a study on the prevalence of obesity-related comorbidities in Danish citizens who have been diagnosed with obesity at a Danish hospital. This was a retrospective observational study with a population comprising all Danish citizens (≥18 years) who have been registered with a specific obesity class diagnosis in the Danish National Patient Register between 2002 and 2018. A total of 86 980 persons with hospital-diagnosed obesity were included in the study population. To investigate how the risk of having comorbidities varies with the degree of obesity, we applied adjusted logistic regression to estimate the odds ratio of having one of the following predefined comorbidities for people with a BMI in obesity classes II and III compared with people with a BMI in obesity class I type 2 diabetes, ischaemic heart disease, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease, hip and knee osteoarthritis, obstructive sleep apnoea and asthma. Comorbidities were defined from ICD-10 diagnosis codes and prescription medication utilization. The odds ratio for obstructive sleep apnoea (OR 1.86 and OR 3.0), type 2 diabetes (OR 1.68 and OR 2.26), hip and knee osteoarthritis (OR 1.29 and OR 1.54) and asthma (OR1.13 and OR 1.25) increased significantly with obesity class (obesity class II relative to I and III relative to I, respectively). The odds ratio of having had at least one comorbidity was estimated to be 1.52 for people with a BMI in obesity class II and 2.10 for people with a BMI in obesity class III compared with people in obesity class I. The risk of obstructive sleep apnoea, type 2 diabetes, hip and knee osteoarthritis, and asthma increased significantly with increasing BMI, highlighting the importance of preventing further weight gain even in individuals who are already living with obesity.

The Efficacy and Safety of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients.

The efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been investigated in kidney transplant recipients (KTRs) with diabetes. We evaluated the impact of SGLT2i in a multicenter cohort of diabetic KTRs. A total of 2083 KTRs with diabetes were enrolled from 6 transplant centers in Korea. Among them, 226 (10.8%) patients were prescribed SGLT2i for >90 d. The primary outcome was a composite outcome of all-cause mortality, death-censored graft failure (DCGF), and serum creatinine doubling. An acute dip in estimated glomerular filtration rate (eGFR) over 10% was surveyed after SGLT2i use. During the mean follow-up of 62.9 ± 42.2 mo, the SGLT2i group had a lower risk of primary composite outcome than the control group in the multivariate and propensity score-matched models (adjusted hazard ratio, 0.43 95% confidence interval, 0.24-0.78 P 0.006 and adjusted hazard ratio, 0.45 95% confidence interval, 0.24-0.85 P 0.013, respectively). Multivariate analyses consistently showed a decreased risk of DCGF and serum creatinine doubling in the SGLT2i group. The overall eGFR remained stable without the initial dip after SGLT2i use. A minority (15.6%) of the SGLT2i users showed acute eGFR dip during the first month, but the eGFR recovered thereafter. The risk factors for the eGFR dip were time from transplantation to SGLT2i usage and mean tacrolimus trough level. SGLT2i improved a composite of all-cause mortality, DCGF, or serum creatinine doubling in KTRs. SGLT2i can be used safely and have beneficial effects on preserving graft function in diabetic KTRs.

Effectiveness of a healthcare-based mobile intervention on sedentary patterns, physical activity, mental well-being and clinical and productivity outcomes in office employees with type 2 diabetes study protocol for a randomized controlled trial.

Prolonged sedentary time is associated with an increased incidence of chronic disease including type 2 diabetes mellitus (DM2). Given that occupational sedentary time contributes significantly to the total amount of daily sedentariness, incorporating programmes to reduce occupational sedentary time in patients with chronic disease would allow for physical, mental and productivity benefits. The aim of this study is to evaluate the short-, medium- and long-term effectiveness of a mHealth programme for sitting less and moving more at work on habitual and occupational sedentary behaviour and physical activity in office staff with DM2. Secondary aims. To evaluate the effectiveness on glycaemic control and lipid profile at 6- and 12-month follow-up anthropometric profile, blood pressure, mental well-being and work-related post-intervention outcomes at 3, 6 and 12 months. Multicentre randomized controlled trial. A sample size of 220 patients will be randomly allocated into a control (n 110) or intervention group (n 110), with post-intervention follow-ups at 6 and 12 months. Health professionals from Spanish Primary Health Care units will randomly invite patients (18-65 years of age) diagnosed with DM2, who have sedentary office desk-based jobs. The control group will receive usual healthcare and information on the health benefits of sitting less and moving more. The intervention group will receive, through a smartphone app and website, strategies and real-time feedback for 13 weeks to change occupational sedentary behaviour. (1) Subjective and objective habitual and occupational sedentary behaviour and physical activity (Workforce Sitting Questionnaire, Brief Physical Activity Assessment Tool, activPAL3TM) 2) Glucose, HbA1c 3) Weight, height, waist circumference 4) Total, HDL and LDL cholesterol, triglycerides (5) Systolic, diastolic blood pressure (6) Mental well-being (Warwick-Edinburgh Mental Well-being) (7) Presenteeism (Work Limitations Questionnaire) (8) Impact of work on employees´ health, sickness absence (6th European Working Conditions Survey) (9) Job-related mental strain (Job Content Questionnaire). Differences between groups pre- and post- intervention on the average value of the variables will be analysed. If the mHealth intervention is effective in reducing sedentary time and increasing physical activity in office employees with DM2, health professionals would have a low-cost tool for the control of patients with chronic disease. ClinicalTrials.gov NCT04092738. Registered September 17, 2019.

Twenty Years of Insulin Gla-100 A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

This systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 UmL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM). A systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest. Seventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n 57) or used in an intensified regimen (n 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet) similar compared with NPH, second-generation basal insulins, co-formulations and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100-based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins. The evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.

Magnesium stable isotope composition, but not concentration, responds to obesity and early insulin-resistant conditions in minipig.

Hypomagnesemia is frequently associated with type 2 diabetes and generally correlates with unfavorable disease progression, but the magnesium status in pre-diabetic conditions remains unclear. Here, the magnesium metabolism is scrutinized in a minipig model of obesity and insulin resistance by measuring variations of the metallome-the set of inorganic elements-and the magnesium stable isotope composition in six organs of lean and obese minipigs raised on normal and Western-type diet, respectively. We found that metallomic variations are most generally insensitive to lean or obese phenotypes. The magnesium stable isotope composition of plasma, liver, kidney, and heart in lean minipigs are significantly heavier than in obese minipigs. For both lean and obese minipigs, the magnesium isotope composition of plasma and liver were negatively correlated to clinical phenotypes and plasma lipoproteins concentration as well as positively correlated to hyperinsulinemic-euglycemic clamp output. Because the magnesium isotope composition was not associated to insulin secretion, our results suggest that it is rather sensitive to whole body insulin sensitivity, opening perspectives to better comprehend the onset of insulin-resistant diabetic conditions.

Concurrent presence of high serum uric acid and inflammation is associated with increased incidence of type 2 diabetes mellitus in Korean adult population.

Although serum uric acid level and systemic inflammation have been highlighted as risk factors for type 2 diabetes mellitus (T2DM), little is known about these associations in the Korean population. Thus, we examined the individual and combined associations of serum uric acid and systemic inflammation (evaluated using high-sensitivity C-reactive protein hs-CRP measurement) with the future risk of T2DM. A total of 4152 Korean adults aged 45-76 years without T2DM, cancer, or gout at baseline in 2007-2008 from the Korean Genome and Epidemiology Study were followed up until 2016. Cox proportional hazard models were used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2DM according to sex-specific tertiles of serum uric acid and hs-CRP levels after adjustment for confounders. During the mean follow-up of 7.3 years, 548 participants developed T2DM. High serum uric acid and hs-CRP levels were independently associated with an increased incidence of T2DM. The multivariable-adjusted HRs (95% CIs) for the incidence of T2DM in the highest tertiles of serum uric acid and hs-CRP were 1.54 (1.24-1.93) and 1.90 (1.48-2.43), respectively. High levels of serum uric acid and hs-CRP in combination were associated with an increased incidence of T2DM (HR 4.69 95% CI 2.81-7.84) compared to low levels of serum uric acid and hs-CRP. These findings suggest that the combination of high serum uric acid and hs-CRP levels was significantly associated with an elevated incidence of T2DM however, their synergistic effects were not observed in middle-aged and elderly Korean adults.

International electronic health record-derived post-acute sequelae profiles of COVID-19 patients.

The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09-1.55), heart failure (RR 1.22, 95% CI 1.10-1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07-1.31), and fatigue (RR 1.18, 95% CI 1.07-1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58-2.76), venous embolism (RR 1.34, 95% CI 1.17-1.54), atrial fibrillation (RR 1.30, 95% CI 1.13-1.50), type 2 diabetes (RR 1.26, 95% CI 1.16-1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09-1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90-3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21-2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04-1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.

Engineering bioactive nanoparticles to rejuvenate vascular progenitor cells.

Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including type-2 diabetes mellitus, hypertension, and cardiovascular disease. A key mechanism by which these complications occur is through stress-induced dysfunction of endothelial progenitor cells (EPCs), including endothelial colony-forming cells (ECFCs). Although several approaches have been previously explored to restore endothelial function, their widespread adoption remains tampered by systemic side effects of adjuvant drugs and unintended immune response of gene therapies. Here, we report a strategy to rejuvenate circulating vascular progenitor cells by conjugation of drug-loaded liposomal nanoparticles directly to the surface of GDM-exposed ECFCs (GDM-ECFCs). Bioactive nanoparticles can be robustly conjugated to the surface of ECFCs without altering cell viability and key progenitor phenotypes. Moreover, controlled delivery of therapeutic drugs to GDM-ECFCs is able to normalize transgelin (TAGLN) expression and improve cell migration, which is a critical key step in establishing functional vascular networks. More importantly, sustained pseudo-autocrine stimulation with bioactive nanoparticles is able to improve in vitro and in vivo vasculogenesis of GDM-ECFCs. Collectively, these findings highlight a simple, yet promising strategy to rejuvenate GDM-ECFCs and improve their therapeutic potential. Promising results from this study warrant future investigations on the prospect of the proposed strategy to improve dysfunctional vascular progenitor cells in the context of other chronic diseases, which has broad implications for addressing various cardiovascular complications, as well as advancing tissue repair and regenerative medicine.

Gut microbiota mediate melatonin signalling in association with type 2 diabetes.

It has been shown that melatonin plays a general beneficial role in type 2 diabetes in rodents but its role in humans is controversial. In the present study, we investigated the association between serum melatonin and type 2 diabetes risk in a southern Chinese population in a case-control study. We also examined the role of gut microbiota in this relationship. Individuals with type 2 diabetes (cases) and healthy individuals (controls) (n2034) were recruited from a cross-sectional study and were matched for age and sex in a case-control study. The levels of serum melatonin were measured and the association between serum melatonin and type 2 diabetes risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n120) in which gut microbial 16S rRNA was sequenced and metabolites were profiled using an untargeted LC-MSMS approach. Higher levels of serum melatonin were significantly associated with a lower risk of type 2 diabetes (OR 0.82 95% CI 0.74, 0.92) and with lower levels of fasting glucose after adjustment for covariates (β -0.25 95% CI -0.38, -0.12). Gut microbiota exhibited alteration in the individuals with type 2 diabetes, in whom lower levels of serum melatonin, lower α- and β-diversity of gut microbiota (p<0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (linear discriminant analysis LDA >2.0) were found. Seven genera were correlated with melatonin and type 2 diabetes-related traits among them Bifidobacterium was positively correlated with serum lipopolysaccharide (LPS) and IL-10, whereas Coprococcus was negatively correlated with serum IL-1β, IL-6, IL-10, IL-17, TNF-α and LPS (Benjamini-Hochberg-adjusted p value false discovery rate (FDR) <0.05). Moreover, altered metabolites were detected in the participants with type 2 diabetes and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR<0.05). Similarly, a significant correlation was found between Trp metabolites and inflammation factors, such as IL-1β, IL-6, IL-10, IL-17, TNF-α and LPS (FDR<0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict type 2 diabetes status (AUC0.804). A higher level of serum melatonin was associated with a lower risk of type 2 diabetes. Gut microbiota-mediated melatonin signalling was involved in this association especially, Bifidobacterium- and Coprococcus-mediated Trp metabolites may be involved in the process. These findings uncover the importance of melatonin and melatonin-related bacteria and metabolites as potential therapeutic targets for type 2 diabetes.

Multi-block data integration analysis for identifying and validating targeted N-glycans as biomarkers for type II diabetes mellitus.

Plasma N-glycan profiles have been shown to be defective in type II diabetes Mellitus (T2DM) and holds a promise to discovering biomarkers. The study comprised 232 T2DM patients and 219 healthy individuals. N-glycans were analysed by high-performance liquid chromatography. The multivariate integrative framework, DIABLO was employed for the statistical analysis. N-glycan groups (GPs 34, 32, 26, 31, 36 and 30) were significantly expressed in T2DM in component 1 and GPs 38 and 20 were related to T2DM in component 2. Four clusters were observed based on the correlation of the expressive signatures of the 39 N-glycans across T2DM and controls. Cluster A, B, C and D had 16, 16, 4 and 3 N-glycans respectively, of which 11, 8, 1 and 1 were found to express differently between controls and T2DM in a univariate analysis Formula see text. Multi-block analysis revealed that trigalactosylated (G3), triantennary (TRIA), high branching (HB) and trisialylated (S3) expressed significantly highly in T2DM than healthy controls. A bipartite relevance network revealed that HB, monogalactosylated (G1) and G3 were central in the network and observed more connections, highlighting their importance in discriminating between T2DM and healthy controls. Investigation of these N-glycans can enhance the understanding of T2DM.