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Effect of obesity on fragility fractures, BMD and vitamin D levels in postmenopausal women. Influence of type 2 diabetes mellitus.

To see the effects of obesity on risk fracture, bone density (BMD), and vitamin D levels in a group of postmenopausal women, and consider how comorbid type 2 diabetes mellitus (T2DM) modifies them. 679 postmenopausal women were grouped into obese and non-obese. Obese women were grouped into those with T2DM and those without. 25(OH)-vitamin D, PTH and BMD were measured, and prevalent fragility fractures were gathered. Obese women had higher prevalence of T2DM, than non-obese women. Levels of 25(OH)-vitamin D were lower and those of PTH higher in obese women, BMD values were higher in obese women. Diabetic-obese women had a higher prevalence of non-vertebral fractures than non-diabetic-obese. Multivariate logistic regression model showed association of fragility fractures with age, total hip BMD, BMI and T2DM. Obese women have higher BMD and lower 25(OH)-vitamin D values (and higher PTH) than non-obese, without diabetes. T2DM confers an increased risk of non-vertebral fractures in postmenopausal obese women.

Coexistent Diabetes Is Associated With the Presence of Adverse Phenotypic Features in Patients With Hypertrophic Cardiomyopathy.

Type 2 diabetes mellitus (T2DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. We sought to investigate whether HCM patients with T2DM comorbidity exhibit adverse cardiac alterations in myocardial energetics, function, perfusion, or tissue characteristics. A total of 55 participants with concomitant HCM and T2DM (HCM-DM) (n 20) or isolated HCM (n 20) and healthy volunteers (HV) (n 15) underwent 31P-MRS and cardiovascular MRI. The HCM groups were matched for HCM phenotype. Mean ± SD European Society of Cardiology sudden cardiac death risk scores were comparable between the HCM groups (HCM 2.2 ± 1.5%, HCM-DM 1.9 ± 1.2% P not significant), and sarcomeric mutations were equally common. HCM-DM patients had the highest median NT-proBNP levels (HV 42 ngL interquartile range 35-66, HCM 298 ngL 157-837, HCM-DM 726 ngL 213-8,695 P < 0.0001). Left ventricular (LV) ejection fraction, mass, and wall thickness were similar between the HCM groups. HCM-DM patients displayed a greater degree of fibrosis burden with higher scar percentage and lower global longitudinal strain compared with HCM patients. PCrATP (the relative concentrations of phosphocreatine and ATP) was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.17 ± 0.49, HCM 1.93 ± 0.38, HCM-DM 1.54 ± 0.27 P 0.002). In a similar pattern, stress myocardial blood flow was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.06 ± 0.42 mLming, HCM 1.74 ± 0.44 mLming, HCM-DM 1.39 ± 0.42 mLming P 0.002). We show for the first time that HCM-DM patients display greater reductions in myocardial energetics, perfusion, and contractile function and higher myocardial scar burden and serum NT-proBNP levels compared with patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and T2DM.

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Effect of metformin on arginine and dimethylarginines in patients with advanced type 2 diabetes A post hoc analysis of a randomized trial.

To study the effect of metformin on plasma levels of arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), indicators of the nitric oxide pathway. In this post hoc analysis of the HOME trial, we analysed plasma levels of arginine, ADMA and SDMA during the 4.3-year follow-up (comparing the effects of metformin versus placebo on top of insulin therapy). Statistical analysis was performed with a mixed model approach, in which simultaneously constant treatment effects were estimated, as well as time-dependent treatment effects. We found that metformin compared with placebo did not affect ADMA or SDMA plasma levels but rapidly decreased arginine plasma levels and hence the arginine to ADMA ratio. The constant treatment effect on ADMA was 0.99 (95% CI 0.97, 1.00) relative to placebo and the time-dependent treatment effect was 1.00 (95% CI 1.00, 1.01). By contrast, the constant treatment effect on arginine was 0.86 (95% CI 0.84, 0.88), with only a minimal time-dependent change of 1.01 (95% CI 1.00, 1.01). The potential benefits of metformin on endothelial function cannot be explained by a decrease in ADMA or by improved global arginine availability. The clinical significance of the decreased arginine plasma levels is not clear and can be harmful or beneficial, depending on the mechanism involved. However, a potential effect of metformin on the nitric oxide pathway is not restricted to the studied metabolites.

Development and implementation of patient-level prediction models of end-stage renal disease for type 2 diabetes patients using fast healthcare interoperability resources.

This study aimed to develop a model to predict the 5-year risk of developing end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) using machine learning (ML). It also aimed to implement the developed algorithms into electronic medical records (EMR) system using Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR). The final dataset used for modeling included 19,159 patients. The medical data were engineered to generate various types of features that were input into the various ML classifiers. The classifier with the best performance was XGBoost, with an area under the receiver operator characteristics curve (AUROC) of 0.95 and area under the precision recall curve (AUPRC) of 0.79 using three-fold cross-validation, compared to other models such as logistic regression, random forest, and support vector machine (AUROC range, 0.929-0.943 AUPRC 0.765-0.792). Serum creatinine, serum albumin, the urine albumin-to-creatinine ratio, Charlson comorbidity index, estimated GFR, and medication days of insulin were features that were ranked high for the ESRD risk prediction. The algorithm was implemented in the EMR system using HL7 FHIR through an ML-dedicated server that preprocessed unstructured data and trained updated data.

Cardiovascular Disease Risk Reduction and Body Mass Index.

Anti-hypertensive and lipid lowering therapy addresses only half of the cardiovascular disease risk in patients with body mass index > 30 kgm Obesity-related insulin resistance, vascular endothelium dysfunction, increased sympathetic nervous systemrenin-angiotensin-aldosterone system activity, and glomerulopathy lead to type 2 diabetes, coronary atherosclerosis, and chronic disease kidney disease that besides hypertension and dyslipidemia increase cardiovascular disease risk. Obesity increases cardiovascular disease risk through multiple pathways. Optimal reduction of cardiovascular disease risk in patients with obesity is likely to require therapy targeted at both obesity and obesity-associated conditions.

Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans a bioinformatics analytic workflow.

Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps systematic review of Gene Expression Omnibus and associated literature identification and classification of differentially expressed genes (DEGs) identification of highly perturbed genes via meta-analysis identification of hub genes via network analysis and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes insulin synthesis and action-related pathways and metabolomics mechanistic associations with apoptosis and immunity-related pathways COVID-19-related gene sets and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.

Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction the EMPEROR-reduced trial.

The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA. The association between SUA and the composite primary outcome of cardiovascular death or hospitalization for worsening HF, its components, and all-cause mortality was investigated in 3676 patients of the EMPEROR-Reduced trial (98.6% of the study cohort). The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricaemia (SUA >5.7 mgdL for women, >7.0 mgdL for men) and in subgroups of patients of tertiles of SUA. Hyperuricaemia was prevalent in 53% of patients with no sex differences. Elevated SUA (highest tertile, mean SUA 9.38 ± 1.49 mgdL) was associated with advanced severity of HF and with worst outcome composite outcome, hazard ratio (HR) 1.64 (95% confidence interval, CI 1.28-2.10) cardiovascular mortality, HR 1.98 (95% CI 1.35-2.91) all-cause mortality, HR 1.8 (95% CI 1.29-2.49), all P < 0.001 in multivariate adjusted analyses, as compared with the lowest tertile. SUA was reduced following treatment with empagliflozin at 4 weeks (vs. placebo -1.12 ± 0.04 mgdL, P < 0.0001) and remained lower throughout follow-up, with a similar reduction in all prespecified subgroups. Empagliflozin reduced events of clinically relevant hyperuricaemia (acute gout, gouty arthritis or initiation of anti-gout therapy) by 32% HR 0.68 (95% CI 0.52-0.89), P 0.004. The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA HR 0.76 (95% CI 0.65-0.88), P < 0.001) and of the change in SUA at 4 weeks HR 0.81 (95% CI 0.69-0.95), P 0.012. As a hypothesis-generating finding, an interaction between SUA and treatment effect suggested a benefit of empagliflozin on mortality (cardiovascular and all-cause mortality) in patients in elevated SUA (P for interaction 0.005 and 0.011, respectively). Hyperuricaemia is common in HF and is an independent predictor of advanced disease severity and increased mortality. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricaemia. The benefit of empagliflozin on the primary outcome was observed independently of SUA.

Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones.

Xanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic profile, mainly as α-glucosidase inhibitors. However, studies concerning the inhibition of both carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase are scarce. Thus, in order to identify some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated together with their commercial parents mangiferin (4), α-mangostin (5) and γ-mangostin (6). The results showed that xanthones exhibited a systematic stronger inhibition against α-glucosidase rather than for α-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of α-amylase, while xanthones 2c, 3b and 3c were the most active against α-glucosidase activity, with IC

Perfluorooctanoic acid promotes pancreatic β cell dysfunction and apoptosis through ER stress and the ATF4CHOPTRIB3 pathway.

Perfluorooctanoic acid (PFOA), a widely used chemical substance, causes an increased risk of human type 2 diabetes (T2D), but its underlying mechanism is not well elucidated. The aim of the present study was to investigate whether PFOA regulates the functions of pancreatic β cells, which are specialized for the biosynthesis and secretion of insulin. The treatment of the mouse pancreatic β cell line (MIN6 cells) with PFOA caused a time- and dose-dependent inhibition of cell viability in CCK-8 assays. Annexin VPI and TUNEL staining results confirmed that exposure to a high PFOA dose (500 μM) promoted apoptosis of β cells, while a low dose (300 μM) had no effects on β cell survival. PFOA treatment, even at a low dose, diminished glucose-stimulated insulin secretion (GSIS) in both primary islet perfusion and MIN6 cell experiments. RNA-sequencing data showed significantly increased expression of endoplasmic reticulum (ER) stress-associated genes, with tribbles homolog 3 (Trib3) ranking first among the altered genes. The activation of ER stress pathways was verified by qRT-PCR assays, and the ATF4CHOPTRIB3 pathway contributed to PFOA-induced β cell damage. The inhibition of TRIB3 expression significantly protected MIN6 cells from PFOA-induced GSIS defects and apoptosis by ameliorating ER stress. These findings reveal a link between ER stress and PFOA-induced β cell defects, opening up a new set of questions about the pathogenesis of T2D due to environmental chemicals.

Improvements in Depression Outcomes Following a Digital Cognitive Behavioral Therapy Intervention in a Polychronic Population Retrospective Study.

Digital mental health interventions have shown promise in reducing barriers to effective care for depression. Depression and related mental disorders are known to be highly comorbid with common chronic physical conditions, such as obesity and type 2 diabetes. While some research has explored the interaction dynamics of treating populations living with both mental and physical disorders, very little is known about such dynamics in digital care. We aimed to examine the effectiveness of a 12-week, therapist-supported, app-based cognitive behavioral therapy program in improving symptoms of depression and anxiety. The studied population included adults with a heavy burden of chronic physical disease, including obesity and type 2 diabetes. A total of 1512 participants with at least moderate depression were enrolled. The treatment cohort consisted of 831 (54.96%) participants who completed a follow-up assessment. The program included structured lessons and tools (ie, exercises and practices) and offered one-on-one weekly video counseling sessions with a licensed therapist for 12 weeks and monthly sessions thereafter. The clinically validated 8-item Patient Health Questionnaire (PHQ-8) and the 7-item Generalized Anxiety Disorder scale (GAD-7) were used to assess depression and anxiety, respectively. Linear mixed-effects modeling was employed to examine changes in depression and anxiety over time. Given correlation among various measures of program usage, a composite variable for depth of usage was used to analyze the correlation between usage and changes in depressive symptoms. Body weight changes from baseline were assessed primarily with digitally connected scales. Out of 831 participants in the treatment cohort, 74.5% (n619) showed a clinically significant reduction in depressive symptom severity after 12 weeks, where follow-up PHQ-8 scores had shifted downward by at least one diagnostic category. In total, 67.5% (n561) of the participants showed a reliable improvement in PHQ-8 scores as measured by the reliable change index. There was an average reduction of 5.9 (SD 5.2) points (P<.001) between baseline and follow-up. Greater program usage was correlated with greater likelihood of reliable improvement in depressive symptoms (odds ratio 1.3, 95% CI 1.1-1.5 P.002). An exploratory analysis of body weight changes with a multilevel, mixed-effect model suggested that reliable improvement in depressive symptoms at follow-up was associated with significantly greater weight loss at 9 months (β-1.11, P.002). The results provide further support that digital interventions can support clinically meaningful improvements in depression. Some form of synergy in treatment of comorbid depression and obesity or diabetes could be studied in future research. The study was limited by postintervention participant attrition as well as the retrospective observational study design.

Risk factors for underlying comorbidities and complications in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.

A novel 6-metabolite signature for prediction of clinical outcomes in type 2 diabetic patients undergoing percutaneous coronary intervention.

Outcome prediction tools for patients with type 2 diabetes mellitus (T2DM) undergoing percutaneous coronary intervention (PCI) are lacking. Here, we developed a machine learning-based metabolite classifier for predicting 1-year major adverse cardiovascular events (MACEs) after PCI among patients with T2DM. Serum metabolomic profiling was performed in a nested case-control study of 108 matched pairs of patients with T2DM occurring and not occurring MACEs at 1 year after PCI, then the matched pairs were 11 assigned into the discovery and internal validation sets. External validation was conducted using targeted metabolite analyses in an independent prospective cohort of 301 patients with T2DM receiving PCI. The function of candidate metabolites was explored in high glucose-cultured human aortic smooth muscle cells (HASMCs). Overall, serum metabolome profiles differed between diabetic patients with and without 1-year MACEs after PCI. Through VSURF, a machine learning approach for feature selection, we identified the 6 most important metabolic predictors, which mainly targeted the nicotinamide adenine dinucleotide (NAD The 6-metabolite model may help for noninvasive prediction of 1-year MACEs following PCI among patients with T2DM.

Bile acids and sphingolipids in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

Anterior segment-optical coherence tomography and diabetic retinopathy Could it be an early biomarker

To measure the corneal thickness (CT), corneal epithelial thickness (CET), and corneal stromal thickness (CST) in patients affected by type 2 diabetes mellitus with good glycemic control and without any signs of diabetic retinopathy using anterior-segment optical coherence tomography (AS-OCT). 60 eyes of 30 diabetic patients and 60 normal eyes of 30 healthy subjects underwent AS-OCT, evaluation of best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit-lamp biomicroscopy, tear film breakup time (TBUT), Schirmer I test and fundus examination. The CT, CET, and CST maps generated corresponded to a 6-mm diameter area of the cornea that was divided into 17 sectors. We compared the CT, CET, and the CST of each sector obtained in the diabetic group with those obtained in the control group. No significant difference in terms of age, gender, BCVA, IOP, TBUT, and Schirmer I test between the two study groups was observed. The CT, CET, and CST in the central section were significantly thickened in diabetic patients than in controls (p<0.001). Also, each paracentral and midperipheral sector was significantly increased in patients compared to controls (p<0.05). The evaluation of the CT, CET, and CST by AS-OCT could be a valid and non-invasive biomarker in patients effected by diabetes mellitus, useful in early diagnosis of diabetic retinopathy.

Effectiveness of physical activity counselling provided for people with type 2 diabetes mellitus in primary healthcare in North Karelia, Finland a register-based evaluation study.

Physical activity (PA) plays a significant role in the treatment of type two diabetes (T2D). This study evaluated the effectiveness of PA counselling in primary healthcare (PHC) on clinical outcome measures in patients with T2D, comparing them with a registry-based controls. The study was carried out in North Karelia, Finland, among PHC clients who have been diagnosed with T2D in 2016-2018. The study population consisted of patients aged 19-87 years diagnosed with T2D (n1803). Altogether 546 patients were referred to the PA educator of whom 521 participated the counselling. In totally 1382 sex, age, time of diagnosis and intervention time-matched controls were used to see the effect of intervention. Patients with T2D followed up in PHC were offered to participate in PA counselling provided by trained PA educators. The number of counselling sessions and their content were tailored according to patients needs and willingness to participate. To assess the effects of PA to management of T2D clinical outcome measures such as weight and Haemoglobin A1c (HbA1c) and lipid levels were assessed using data from electronic patient records. Each patient was followed up from records at least for a year. Weight and body mass index (BMI) decreased in both groups and mean yearly changes did not differ between the groups. HbA1c levels declined in the intervention and increased in the control group with statistically significant difference in the mean yearly change between the groups (p0.001). The low-density lipoprotein declined in both groups. The decline was bigger in the intervention group, but the difference did not quite reach the statistical significance (p0.096). This study shows that PA counselling in PHC offers significant benefits in the treatment outcomes of T2D although no significant declines were not observed in the weight or BMI.

Genetic variation in

Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Patients with alcohol-related cirrhosis and HCC (cases n1214) and controls without HCC (n1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Associations with variants rs738409 in This study identifies rs2242652 in

Machine Learning-Derived Prenatal Predictive Risk Model to Guide Intervention and Prevent the Progression of Gestational Diabetes Mellitus to Type 2 Diabetes Prediction Model Development Study.

The increasing prevalence of gestational diabetes mellitus (GDM) is concerning as women with GDM are at high risk of type 2 diabetes (T2D) later in life. The magnitude of this risk highlights the importance of early intervention to prevent the progression of GDM to T2D. Rates of postpartum screening are suboptimal, often as low as 13% in Asian countries. The lack of preventive care through structured postpartum screening in several health care systems and low public awareness are key barriers to postpartum diabetes screening. In this study, we developed a machine learning model for early prediction of postpartum T2D following routine antenatal GDM screening. The early prediction of postpartum T2D during prenatal care would enable the implementation of effective strategies for diabetes prevention interventions. To our best knowledge, this is the first study that uses machine learning for postpartum T2D risk assessment in antenatal populations of Asian origin. Prospective multiethnic data (Chinese, Malay, and Indian ethnicities) from 561 pregnancies in Singapores most deeply phenotyped mother-offspring cohort study-Growing Up in Singapore Towards healthy Outcomes-were used for predictive modeling. The feature variables included were demographics, medical or obstetric history, physical measures, lifestyle information, and GDM diagnosis. Shapley values were combined with CatBoost tree ensembles to perform feature selection. Our game theoretical approach for predictive analytics enables population subtyping and pattern discovery for data-driven precision care. The predictive models were trained using 4 machine learning algorithms logistic regression, support vector machine, CatBoost gradient boosting, and artificial neural network. We used 5-fold stratified cross-validation to preserve the same proportion of T2D cases in each fold. Grid search pipelines were built to evaluate the best performing hyperparameters. A high performance prediction model for postpartum T2D comprising of 2 midgestation features-midpregnancy BMI after gestational weight gain and diagnosis of GDM-was developed (BMIGDM CatBoost model AUC0.86, 95% CI 0.72-0.99). Prepregnancy BMI alone was inadequate in predicting postpartum T2D risk (ppBMI CatBoost model AUC0.62, 95% CI 0.39-0.86). A 2-hour postprandial glucose test (BMI2hour CatBoost model AUC0.86, 95% CI 0.76-0.96) showed a stronger postpartum T2D risk prediction effect compared to fasting glucose test (BMIFasting CatBoost model AUC0.76, 95% CI 0.61-0.91). The BMIGDM model was also robust when using a modified 2-point International Association of the Diabetes and Pregnancy Study Groups (IADPSG) 2018 criteria for GDM diagnosis (BMIGDM2 CatBoost model AUC0.84, 95% CI 0.72-0.97). Total gestational weight gain was inversely associated with postpartum T2D outcome, independent of prepregnancy BMI and diagnosis of GDM (P.02 OR 0.88, 95% CI 0.79-0.98). Midgestation weight gain effects, combined with the metabolic derangements underlying GDM during pregnancy, signal future T2D risk in Singaporean women. Further studies will be required to examine the influence of metabolic adaptations in pregnancy on postpartum maternal metabolic health outcomes. The state-of-the-art machine learning model can be leveraged as a rapid risk stratification tool during prenatal care. ClinicalTrials.gov NCT01174875 httpsclinicaltrials.govct2showNCT01174875.

Evaluation of Early Postoperative Period Results of Patients With Type 2 Diabetes Taking Oral Anti-Diabetics Or Insulin Medications, With Microalbuminuria and Normal Creatinine Levels After Coronary Artery Bypass.

Acute kidney injury (AKI) is one of the most important complications after cardiac surgery and is one of the main causes of morbidity and mortality. Diabetes mellitus also is one of the main risk factors for renal dysfunction in coronary artery bypass graft (CABG). In this study, we aimed to compare the early postoperative period results of type 2 diabetes patients taking oral antidiabetics (OAD) or insulin medications, with microalbuminuria and normal creatinine levels after CABG. Eighty patients with type 2 diabetes and taking OAD or receiving insulin medication all with normal creatinine levels with microalbuminuria were included in this study. Preoperative creatinine values of the patients, albumin levels in spot urine, creatinine levels on the postoperative 3rd day, duration of ventilation, amount of drainage, length of stay in the intensive care unit, length of stay in the hospital, mediastinitis, and mortality rates were recorded. A statistically significant increase in creatinine was found in both taking OAD type 2 diabetes and insulin medication with microalbuminuria. When the two groups were compared with each other, the increase in creatinine levels of the patients using insulin was higher than the patients taking OAD. It also was statistically significant. According to the result of our study, it can be suggested that postoperative creatinine elevation is observed in patients with type 2 diabetes mellitus with microalbuminuria and with normal creatinine levels, either having insulin medication or not. The elevation is higher in patients having insulin medication, while other results are similar, except for impaired renal function.

Liver function markers predict cardiovascular and renal outcomes in the CANVAS Program.

Raised liver function tests (LFTs) have been correlated with multiple metabolic abnormalities and variably associated with cardiorenal outcomes. We sought to systematically test the relationship between LFT levels within the accepted range and major cardiorenal outcomes in a large clinical trial in type 2 diabetes, and the possible impact of placebo-controlled canagliflozin treatment. We measured serum alanine aminotransferase (ALT), aspartic aminotransferase (AST), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin concentrations in 10,142 patients, at baseline and repeatedly over follow-up. The relation of LFTs to first hospitalized heart failure (HHF), cardiovascular (CV) and all-cause mortality, and progression of renal impairment was investigated using multivariate proportional-hazards models. In univariate association, ALT was reciprocally predictive, and ALP was positively predictive, of all adjudicated outcomes γGT also was directly associated with CV-but not renal-outcomes. In multivariate models including all 5 LFTs and 19 potential clinical confounders, ALT was independently associated with lower, and γGT with higher, CV outcomes risk. Canagliflozin treatment significantly reduced ALT, AST, and γGT over time. In a fully adjusted model including updated LFT levels and treatment, γGT was independently associated with CV and all-cause mortality, ALP with renal dysfunction progression, and canagliflozin treatment with significant reduction in HHF and renal risk. Higher γGT levels are top LFT markers of risk of HHF and death in patients with diabetes and high CV risk, while ALT are protective. Canagliflozin lowers the risk of HHF and renal damage independently of LFTs and potential confounders.

Assessment of the relationship between 25-hydroxyvitamin D and albuminuria in type 2 diabetes mellitus.

Diabetic nephropathy occurs in about one-third of diabetic patients. This health problem is characterized by increased urinary albumin excretion, leading to decreased glomerular filtration rate and renal failure. In this regard, previous investigations have revealed the possibility of a relationship between vitamin D deficiency and diabetic nephropathy. The present study assessed the relationship between vitamin D deficiency and albuminuria in patients with type 2 diabetes. This study was conducted with 200 participants with type 2 diabetes mellitus from December 2019 to January 2021. The patients 25-hydroxyvitamin D (25OHD) serum level and urinary albumin-to-creatinine ratio (UACR) were measured concurrently. Afterward, the subjects were divided into three groups based on their albuminuria level. Finally, 25OHD serum level and other clinical characteristics were compared among these albuminuria groups, and the relation between albuminuria level and 25OHD was analyzed. The prevalence of vitamin D deficiency in macroalbuminuric patients (UACR≥300 mgg) was 61.8%, and in microalbuminuric (30 ≤ UACR< 300 mgg) and normoalbuminuric groups (UACR< 30 mgg) was 33.3% and 24%, respectively. Further analysis revealed a significant negative relationship between 25OHD and albuminuria(r - 0.257, p-value< 0.001). According to ROC curve analysis, a 25OHD level ≤ 21 ngml was considered an optimal cut-off point value for having macroalbuminuria in diabetic patients. The current study evaluates the relation between vitamin D deficiency and the prevalence of albuminuria in the setting of diabetes. Overall, the prevalence of macroalbuminuria increased when the 25OHD serum level was less than 20 ngml.

Etiology of Persistent Microalbuminuria in Nigeria (PMICRO study) protocol and study design.

Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4-8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population. In Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria. The findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Ocular Surface and Tear Cytokine Changes after Cataract Surgery in Patients with Type 2 Diabetes.

To evaluate changes in ocular surface indices and tear cytokines after cataract surgery in type 2 diabetic patients. Ocular surface indices and concentrations of tear cytokines (MCP-1, IL-6, IL-8, and VEGF) were evaluated at baseline and one week and one month postoperatively. Patients (30 diabetic and 30 control) were enrolled. In the diabetic group, changes in ocular symptom and tear breakup time remained until one month postoperatively ( Diabetic patients can experience more prominent changes after surgery and these changes were accompanied by an increase of several tear cytokines.

Forming new health behavior habits during weight loss maintenance-The PREVIEW study.

Changing lifestyle habits to achieve and maintain weight loss can be effective in prevention of Type II diabetes. Ability to resist temptations is considered one of the key factors in behavior change. This study examined how habit strength, motivation, and temptations for an energy-dense diet developed during the maintenance stage of a behavior modification intervention tool. Participants with prediabetes and overweightobesity were recruited in the two-phase trial PREVIEW with the aim to achieve ≥ 8% body weight loss over 2 months and maintain weight loss over a subsequent 34-month period. The four-stage intervention (PREVIEW Behavior Modification Intervention Toolbox, or PREMIT) supported participants in weight maintenance. Uni- and multivariate analyses were completed from the beginning of the PREMIT maintenance stage (Week 26 of the PREVIEW trial) with 962 individuals who completed the trial. Habit strength and ability to resist temptations increased during the early PREMIT adherence stage (Weeks 26 to 52) before plateauing during middle (Weeks 52 to 104) and late (Weeks 104 to 156) PREMIT adherence stages. Higher habit strength for energy-dense diet was significantly associated with larger weight regain ( Changing diet habits is a complex, multifactorial process, with participants struggling at least with some aspects of weight maintenance. Habits against consuming energy-dense, sweet, and fatty food appeared effective in protecting against weight regain. The observed effect sizes were small, reflecting the complexity of breaking old habits and forming new ones to support long-term maintenance of weight loss. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

With a resurgence of covalent drugs, there is an urgent need for the identification of new moieties capable of cysteine bond formation. Herein, we report on the

Association Between Metformin and Alzheimers Disease A Systematic Review and Meta-Analysis of Clinical Observational Studies.

As one of the widely used drugs for the management of type 2 diabetes mellites (T2DM), metformin is increasingly believed to delay cognitive deterioration and therapeutically for Alzheimers disease (AD) patients especially those with T2DM. However, studies of the potential neuroprotective effects of metformin in AD patients have reported contradictory results. This study aimed to evaluate the association between metformin and the risk of developing AD. We systematically searched the PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases to identify clinical observational studies on the relationship between AD risk and metformin use published before December 20, 2021. Two investigators independently screened records, extracted data, and assessed the quality of the studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated using random-effect models. After screening a total of 1,670 records, we included 10 studies involving 229,110 participants. The meta-analysis showed no significant association between AD incidence and metformin exposure (OR 1.17, 95% CI 0.88-1.56, p 0.291). However, subgroup analysis showed that among Asians, the risk of AD was significantly higher among metformin users than those who did not (OR 1.71, 95% CI 1.24-2.37, p 0.001). The available evidence does not support the idea that metformin reduces risk of AD, and it may, in fact, increase the risk in Asians. Further well-designed randomized controlled trials are required to understand the role played by metformin and other antidiabetic drugs in the prevention of AD and other neurodegenerative diseases.

Juzentaihoto Suppresses Muscle Atrophy in KKAy Mice.

In obese patients with type 2 diabetes, reduced insulin sensitivity, increased production of inflammatory cytokines, and increased oxidative stress were observed, which lead to decreased protein synthesis and increased proteolysis in the skeletal muscles. Juzentaihoto (JTT) is herbal medicine and we have previously reported that the administration of JTT hot water extract alleviates skeletal muscle atrophy in a mouse model with streptozotocin-induced type 1 diabetes. In this study, we evaluated the inhibitory effects of JTT on muscle atrophy in a mouse model with obesity and type 2 diabetes. JTT was administered to KKAy mice with type 2 diabetic obesity and its effects on the skeletal muscles were evaluated. After JTT administration in KKAy mice, the wet weight and muscle fibre cross-sectional area of gastrocnemius increased and the time duration of exercise in the rotarod test improved. In addition, the serum levels of tumour necrosis factor-α and interleukin-6 decreased, adiponectin levels increased, and homeostasis model assessment for insulin resistance improved. Furthermore, JTT administration decreased the mRNA levels of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1), increased the mRNA levels of Sirtuin1 in gastrocnemius. Our results suggest that JTT improves insulin resistance, suppresses inflammation, and reduces oxidative stress in KKAy mice, thereby suppressing skeletal muscle atrophy. JTT administration in clinical practice is expected to improve muscle atrophy in patients with obesity and type 2 diabetes.

Deprescribing in Danish clinical treatment guidelines.

Lack of clinical guidance constitutes a significant barrier to deprescribing. Within Danish clinical guidelines on treatment of dementia, type 2 diabetes, hypertension, and osteoporosis, only limited attention was given to deprescribing. For dementia, type 2 diabetes, and osteoporosis, guidance was primarily focused on when to consider and implement deprescribing, with limited practical guidance on how to deprescribe. No guidance for deprescribing antihypertensives was identified. This highlights a need to consider deprescribing more broadly when developing and updating clinical guidelines, as argued in this review.

Lipid characteristics of fatty liver induced by high expression of Golgi protein 73.

Fatty liver disease is a common chronic liver disease which is mainly induced by abnormal lipid metabolism. To find out the effect of GP73 on lipid metabolism in the liver, we constructed a high GP73 expression liver model through a tail vein injection of AAV-GP73 into eight-week-old C57BL6J mice. Liver lipid metabolomics analysis showed that lipids in the liver of mice, especially the triglycerides, were significantly increased. In addition, kyoto encyclopedia of genes and genomes enrichment analysis showed that GP73 altered lipid metabolites profile that may further disturb many signaling pathways related to cellular metabolism. The diseases linked to type II diabetes, non-alcoholic fatty liver disease (NAFLD) and choline metabolism in cancer cells were more likely to be dysregulated. Thus, GP73 may induce fatty liver by regulating lipid metabolism and promoting lipid accumulation in the liver.

Is serum vitamin D associated with diabetic retinopathy and its severity or with diabetes itself

Vitamin D (VitD) deficiency, which is found in approximately one-third of the population of the world, may play a role in the pathogenesis of diabetic retinopathy. Physicians following diabetes patients should be aware of this relationship and should refer patients to for ophthalmic care for control in a timely manner. Diabetic retinopathy is one of the most common complications of diabetic microvascular disease. VitD deficiency has been implicated in the pathogenesis and progression of diabetes and may have a role in development and severity of diabetic retinopathy. The aim of this study was to examine the relationship of serum VitD and some laboratory parameters with the presence of diabetes and retinopathy. In this study, which has a retrospective epidemiological study design, comprehensive ophthalmologic examination data from the eye clinic, laboratory data from fasting blood tests, and internal medicine outpatient clinic examination data were reviewed. All participants were divided into four groups 109 healthy controls, and 165 patients with type 2 diabetes of whom 54 did not have retinopathy, 64 had proliferative diabetic retinopathy, and 47 had non-proliferative diabetic retinopathy. Participants were also divided into four groups according to their serum VitD levels. Serum 25(OH)D, HbA In the whole study cohort, 152 (55.5%) were female and 122 (44.5%) were male. A statistically significant difference was observed in VitD between the healthy group and the diabetic and proliferative diabetic retinopathy groups (p ≤ 0.001). However, no significant correlation was observed between the presence of diabetes and retinopathy and serum VitD in logistic regression analyses (p > 0.05). Diabetic patients have lower 25(OH)D than non-diabetic patients and there is no direct relationship between 25(OH)D and the development of diabetic retinopathy.

Role of Macrophage in Type 2 Diabetes Mellitus Macrophage Polarization a New Paradigm for Treatment of Type 2 Diabetes Mellitus.

Metabolic diseases such as type 2 diabetes mellitus are usually in association with meta-inflammation. β-cell failure is a marked feature observed in the pathogenesis of type 2 diabetes mellitus. Type 2 diabetes mellitus (T2DM) is a heterogeneous situation that is accompanied with not only defective insulin secretion but also peripheral insulin resistance. β-cells are the primary organ for insulin secretion hence, it is crucial to maintain a significant β-cell mass in response to a variety of changes. Insulin resistance is a chief cause of T2DM leading to increased free fatty acid (FFA) levels which in turn elevates β-cell mass and insulin secretion as a compensation for insulin insensitivity. Recently, it has been established that amplified numbers of innate immune cells, cytokines, and chemokines result in detrimental effects on islets in such chronic conditions. Macrophage migration inhibitory factor (MIF) is the lymphokine that results in the prevention of arbitrary migration of macrophages and assembles macrophages at inflammatory loci. Inflammation is known to trigger monocytes in differentiating into macrophages. Progress of complications associated with type 2 diabetes mellitus, as indicated through recent findings, is also dependent on the buildup of macrophages in tissues vulnerable to diabetic injury. The present article scientifically evaluates the present knowledge concerning the mechanisms of recruitment of monocyte and macrophage-mediated injury in complications associated with type 2 diabetes mellitus. It also gives a description of some of the established and experimental therapies that might bring about a reduction in these inflammatory complications. Recent discoveries in the field of drug delivery have facilitated phenotype-specific targeting of macrophages. In this review, it is highlighted that the pathophysiology of type 2 diabetes mellitus, how macrophage induces type 2 diabetes mellitus and potential therapeutics for type 2 diabetes mellitus via macrophage-specific delivery.

Structural and functional retinal changes in patients with type 2 diabetes without diabetic retinopathy.

The characteristics of the early changes in preclinical diabetic retinopathy (DR) are poorly known. This study aimed to analyse the changes in the structure and function of the fundus in diabetic patients without diabetic retinopathy (NDR). This prospective study enrolled patients with type 2 diabetes and healthy controls from April to December 2020. Retinal sensitivity was measured by microperimetry. The peripapillary retinal nerve fibre layer (p-RNFL) thickness, macular retinal thickness, and retinal volume were measured by optical coherence tomography (OCT). The vessel density (VD) and perfusion density (PD) of the peripapillary area, as well as the foveal avascular zone (FAZ) area, FAZ perimeter, and FAZ circularity, were measured by optical coherence tomographic angiography (OCTA). A total of 71 cases (100 eyes) were enrolled in the study, including 34 cases (51 eyes) in the NDR group and 37 cases (49 eyes) in the control group. The mean retinal sensitivity was lower in the NDR group than in the control group for all sectors (all The structure (p-RNFL thickness, VD, and PD) and function (retinal sensitivity) display some changes in diabetic patients even if they had not been found to have DR.Key messagesDecreased retinal sensitivity was observed in diabetic patients before the onset of diabetic retinopathy.Compared with the control group, we found the changes in vessel density or perfusion density in a certain area, whether in SCP, DCP, or RPCP in the NDR group.Before the onset of diabetic retinopathy, the structure and function of the retina in diabetic patients had changed.

Post-pancreatitis diabetes mellitus insight on optimal management with nutrition and lifestyle approaches.

Pancreatitis is the leading gastrointestinal cause of hospitalizations. There are multiple short- and long-term complications associated with pancreatitis. Post-pancreatitis diabetes mellitus (PPDM) is one of the less explored complications of pancreatitis. Nonetheless, it has attracted considerable attention during the last decade. PPDM is now the second most common cause of new-onset diabetes mellitus (DM) in adults after type II DM surpassing type 1 DM. However, there exists a knowledge gap amongst practitioners regarding diagnosis, complications, and management of PPDM. In this narrative, we aim to provide a brief review regarding risks, diagnosis and management of PPDM with a special focus on dietary and lifestyle management strategies.KEY MESSAGESPost-pancreatitis diabetes mellitus (PPDM) is now the second most common cause of new-onset diabetes mellitus (DM) in adults after type II DM surpassing type 1 DM.New-onset diabetes in patients with pancreatitis could also be an early marker of occult pancreatic malignancy.Management of PPDM is complex and requires a team-based approach including gastroenterologists, endocrinologists, primary care physicians, nutritionists, and behavioural health specialists.

Sphingomyelin profiling in patients with diabetes could be potentially useful as differential diagnostics biomarker A pilot study.

Autoimmune diabetes (AD) in adults includes both the classical form of type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). LADA shares clinical and metabolic features with type 1 and type 2 diabetes mellitus (T2DM). Ceramide (Cer) levels negatively correlate with insulin sensitivity in humans and animal models. However, only a few studies have focused on other sphingolipids, including sphingomyelin (SM). Therefore, we determined sphingolipids in patients with newly diagnosed diabetes as possible diagnostic biomarkers. We evaluated sphingolipids in a cohort of 59 adults with newly diagnosed diabetes without prior hypoglycemic pharmacotherapy to distinguish diabetes mellitus types and for precise LADA definition. All patients with newly diagnosed diabetes were tested for the concentrations of individual Cer and SM species by gas-liquid chromatography. The study included healthy controls and patients with T1DM, T2DM and LADA. SM species were significantly altered in patients with newly diagnosed diabetes compared to healthy controls. SM-C160, C161, -C180, -C181, -C182, -C183, -C204, and -C226 species were found to be significantly elevated in LADA patients. In contrast, significant differences were observed for Cer species with saturated acyl chains, especially Cer-C140, -C160, -C180 (AD and T2DM), -C220, and -C240 (T1DM). Following ROC analysis, SM-C160, and particularly -C181, and -C204 may be supportive diagnostic markers for LADA. SM profiling in patients with newly diagnosed diabetes could be potentially helpful for differential diagnosis of LADA, T1DM, and T2DM in more challenging cases.

Exercise mode influences post-exercise glucose sensitivity and insulin clearance in young, healthy males and females in a sex-dependent manner A randomized control trial.

Type 2 diabetes (T2D) risk is lower in females than males. It has been reported that females have greater pancreatic 𝛽-cell function than males, which may at least in part contribute to the T2D risk in females. 𝛽-cell function is influenced by exercise training however, previous trials comparing 𝛽-cell function between the sexes have not included participants matched for training status. Furthermore, the acute effects of different modes of exercise on 𝛽-cell function, and whether sex inherently influences these effects, are largely unexamined. Males and females (12sex) completed a 120-min oral glucose tolerance test (OGTT) at rest (CON) and following acute bouts of high-intensity interval exercise (HIIE), moderate intensity continuous (MIC) exercise, and low-load high-repetition (LLHR) resistance exercise to assess whether sex inherently influences baseline andor post-exercise pancreatic function in the absence of pathology. We found no sex differences in basal pancreatic 𝛽-cell function. Females had greater basal insulin clearance following MIC exercise compared to males (p 0.01) and males tended to have a higher potentiation ratio following HIIE (p 0.07). Females also had lower glucose sensitivity following MIC exercise compared to HIIE (p 0.007) and LLHR (p 0.003). Insulin clearance during the OGTT was greater following HIIE as compared with CON and MIC exercise (p 0.02). 2-H oral glucose insulin sensitivity was greater following LLHR compared to CON (p 0.01). Acute bouts of different modes of exercise do not differentially influence 𝛽-cell function but do influence insulin clearance and insulin sensitivity. Therefore, sex and exercise mode interact to differentially influence insulin clearance and glucose sensitivity.

Evaluation of the Clinical Efficacy of the Treatment of Overweight and Obesity in Type 2 Diabetes Mellitus by the Telemedicine Management System Based on the Internet of Things Technology.

To explore the application value of medical intelligent electronic system under the background of Internet of Things in the clinical study of the treatment of overweightobesity in type 2 diabetes mellitus (T2DM) with empagliflozin combined with liraglutide 50 overweight and obese adult T2DM patients in our hospital were randomly divided into the combined group and the control group, 25 cases in each group. The control group was treated with liraglutide alone, while the combined group was treated with empagliflozin on the basis of liraglutide. Based on the Internet of Things technology, with diabetes management as the core, the functions of information collection, transmission, and storage of T2DM patients are realized. Doctors pass the diabetes management plan to T2DM patients through the platform, supervise the implementation, and finally compare the clinical efficacy of the two groups. Compared with before treatment, the body mass index (BMI), fasting blood glucose (FPG), postprandial blood glucose (2hPG), glycosylated hemoglobin (HbAlc), islet beta cell secretion function index (HOMA- The telemedicine management system based on Internet of Things technology can improve patients self-management ability and provide a new choice for individualized treatment of overweightobesity T2DM patients. The combination therapy of empagliflozin and liraglutide can effectively reduce blood sugar, weight, blood pressure, blood lipid, and hypoglycemia and effectively improve insulin resistance and secretion function of islet

Efficacy and Safety of Insulin DegludecInsulin Aspart (IDegAsp) in Type 2 Diabetes Systematic Review and Meta-Analysis.

Type 2 diabetes mellitus is a prevalent metabolic disease requiring tight glycemic control of basal and postprandial glucose levels. Treatment intensification using separate basal and bolus injections increased the number of injections and reduced cost-effectivity, leading to decreased compliance and failure of glycemic control. Insulin DegludecInsulin Aspart (IDegAsp), a novel premix of basal and bolus insulin, is one of the potential treatments for reducing the number of injections. However, its efficacy and safety have not been reviewed clearly. Therefore, this systematic review aims to compare the efficacy and safety of IDegAsp with standard basal and basal plus bolus insulin regimens. A systematic review of four databases (Pubmed, Scopus, Science Direct, and Proquest) was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Search results were screened by eligibility criteria and critically appraised by the Oxford Centre for Evidence-Based Medicine (CEBM) tool and the Cochrane risk-of-bias

The Nexus Between Diabetes and Depression A Narrative Review.

Comorbid diabetes and depression are a significant public health burden as the consequences of both diseases are worsened by each other. In this study, we have compiled and analyzed findings from various studies to demonstrate that diabetes has a strong association with depression. Both have a significant impact on the quality of life, although the exact mechanisms through which these two chronic diseases affect each other remain unknown. This article discussed the shared etiological factors of comorbidity between diabetes and depression, including physiological (e.g., deregulation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS) overactivity, microvascular dysfunction, arterial stiffening, inflammation, and cytokines), behavioral (e.g., diet and lifestyle modifications), and environmental (e.g., childhood adversity, poverty, and neighborhood environment). Included data from a range of settings have suggested that the prognosis of both diabetes and depression, in terms of complications, treatment efficacy, morbidity, and mortality, is worse for either disease when they occur concurrently than individually. The implication for the physical, mental, and social well-being of depression in diabetes causes poor self-care and adherence to medical treatment. This article also highlights the importance of regular screening and prompts the treatment of comorbid diabetes and depression with pharmacotherapy, face-to-face psychotherapy, and non-face-to-face models of alternative psychological interventions, including information and communication technologies (ICTs), computer-based diabetes self-management interventions, and digital mental health intervention, to improve the outcomes of both diseases.

17β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation of Mesenteric Arteries in Ovariectomized UC Davis Type 2 Diabetes Mellitus Rats in Prediabetic State.

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted with either placebo or 17β-estradiol (E

Efficacy and Safety of Non-Steroidal Mineralocorticoid Receptor Antagonists in Patients With Chronic Kidney Disease and Type 2 Diabetes A Systematic Review Incorporating an Indirect Comparisons Meta-Analysis.

Dietary knowledge and practice and its associated factors among type 2 diabetes patients on follow-up at public hospitals of Dire Dawa, Eastern Ethiopia.

This study tried to assess the level of dietary knowledge and practice and associated factors among type 2 diabetes mellitus patients in public hospitals of Dire Dawa, Ethiopia. A facility-based cross-sectional study was conducted among 253 type 2 diabetes mellitus patients visiting follow-up clinic in public hospitals selected by systematic random sampling. Primary data were collected by face-to-face interview and checklist. The collected data were entered into SPSS version 22 and analyzed using proportion, percentage, and mean and standard deviation. Bivariate logistic regression analysis was used to identify candidate variables affecting dietary practice. Finally, all candidate independent variables were further adjusted on multivariate regression analysis with adjusted odds ratio and 95% confidence interval to identify factors independently associated with dietary practice. The level of poor dietary practice among type 2 diabetes mellitus patients was found to be 53.8%. Around 78.8% of participants had fasting blood sugar level ⩾130 mgdL, and 52.8% found to have poor dietary knowledge. Moreover, there was no up-to-date nutritional guideline in follow-up clinic. Not getting nutrition advice from doctorsnurses, low duration of follow-up, lack of family support, and despondency were significantly associated with poor dietary practice ( More than half of diabetes patients had poor dietary practice, which is in contrary with international recommendations of diabetic self-care. Habit of eating fruits and vegetables was poorly practiced and also patients knowledge of recommended nutrition was poor. Therefore, provision of robust nutritional education and counseling service, a system to strengthen family support as well as psychosocial support, is highly recommended.

Self-care practices and correlates among patients with type 2 diabetes in Eastern Ethiopia A hospital-based cross-sectional study.

This study investigated the level and correlates of self-care practices among patients with type 2 diabetes on follow-up in two public hospitals in Harar, Eastern Ethiopia. We conducted a hospital-based cross-sectional study on adult patients with type 2 diabetes, surveying diabetes self-care practices using a 15-item Summary of Diabetes Self-Care Activities. Responses ranged from 0 to 7 days, and a composite score was computed representing the mean days of diabetes self-care practices. A generalized Poisson regression model with robust variance was used. The association between the diabetes self-care practices and correlates was examined using the incidence rate ratio with a 95% confidence level. The statistical significance was set at a p value of ⩽0.05. This study included 879 patients with type 2 diabetes. The overall mean (standard deviation) diabetes self-care practices were 3.7 ± 1.1 days out of the recommended 7 days, indicating low self-care practices. After controlling for other variables, tertiary educational level (incidence rate ratio 1.06 95% confidence interval 1.01, 1.12), adequate diabetes knowledge (incidence rate ratio 1.04 95% confidence interval 1.00, 1.08), moderate (incidence rate ratio 1.07 95% confidence interval 1.02, 1.11) and high perceived self-efficacy (incidence rate ratio 1.14 95% confidence interval 1.09, 1.13) (incidence rate ratio 1.07 95% confidence interval 1.02, 1.11), high to marginal food security (incidence rate ratio 1.13 95% confidence interval 1.03, 1.24), and receiving dietary advice (incidence rate ratio 1.11 95% confidence interval 0.06, 1.15) were positively correlated with diabetes self-care practices. A history of hospitalization, on the other hand, was found to be inversely correlated with diabetes self-care practices (incidence rate ratio 0.94 95% confidence interval 0.88, 0.99). The study indicated that adherence of patients with type 2 diabetes to the recommended self-care practices was considerably low. Therefore, tailored diabetes self-management education to enhance self-efficacy and diabetes self-care practices must be in place. This can be achieved through the system or individual-based integrated intervention efforts.

Gestational Diabetes Mellitus Among Asians - A Systematic Review From a Population Health Perspective.

Since Asians are particularly vulnerable to the risk of gestational diabetes mellitus (GDM), the lifecourse health implications of which are far beyond pregnancy, we aimed to summarize the literature to understand the research gaps on current GDM research among Asians. We systematically searched the articles in PubMed, Web of Science, Embase, and Scopus by 30 June 2021 with keywords applied on three topics, namely GDM prevalence in Asians, GDM and maternal health outcomes in Asians, and GDM and offspring health outcomes in Asians. We observed that Asian women (natives and immigrants) are at the highest risk of developing GDM and subsequent progression to type 2 diabetes among all populations. Children born to GDM-complicated pregnancies had a higher risk of macrosomia and congenital anomalies (i.e. heart, kidney and urinary tract) at birth and greater adiposity later in life. This review summarized various determinants underlying the conversion between GDM and long-term health outcomes in Asian women, and it might shed light on efforts to prevent GDM and improve the lifecourse health in Asians from a public health perspective. Prospero, CRD42021286075.

Influence of Dietary Salt Intake on T2D Treatment.

To what extent patients undergoing long-term T2D treatment are affected by dietary salt intake has not been completely investigated. We aimed to investigate the influence of dietary salt intakes on T2D treatment, including glucose-lowering effect and indices related to T2D progression. The study recruited 1090 patients with T2D at Ningbo City First Hospital from January 1, 2018, to December 30, 2021. We compared their one-year follow-up outcomes in terms of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), blood pressure, obesity, and prevalence of retinopathy and neuropathy among groups with different dietary salt intakes. The 1090 patients consisted of 287(26.3%) decreasing-, 190(17.4%) increasing-, 175(16.0%) steadily low-, 243(22.3%) steadily medium-, and 195(17.9%) steadily high-dietary salt intake patients. Compared to increasing-, steadily medium-, and steadily high-dietary salt intake patients, decreasing and steadily low salt intake led to lower baseline FBG, HbA1c, systolic blood pressure (SBP), BMI, and visceral fat area (VFA) (all p<0.05), to a larger decrease in FBG, HbA1c, SBP, BMI, and VFA after one-year treatment (all p<0.05), as well as to a slightly lower prevalence of retinopathy and a significantly lower prevalence of neuropathy. The steadily low salt patients had lower urine albumincreatinine ratio (UAR) both at baseline and after treatment. Notably, the fasting insulin in the steadily low salt group was higher than the remaining groups after treatment (p<0.01). The present study concludes that lowered dietary salt intake benefits T2D treatment in multiple aspects, including main treatment targets such as FBG and HbA1c, and indices reflecting potential complications of T2D, including BMI, VFA, SBP, UAR, retinopathy, and neuropathy. www.ClinicalTrials.gov, identifier NCT03811470.

Multi-Faceted Influence of Obesity on Type 1 Diabetes in Children - From Disease Pathogenesis to Complications.

The prevalence of overweight and obesity among youth patients with diabetes type 1 is increasing. It is estimated, that even up to 35% of young patients with this type of diabetes, considered so far to be characteristic for slim figure, are overweight or even obese. General increase of obesity in childrens population complicates differential diagnosis of the type of diabetes in youths. Coexistence of obesity has clinical implications for all stages of diabetes course. It is confirmed that obesity is the risk factor for autoimmune diabetes, and is connected with the earlier onset of diabetes in predisposed patients. Many diabetic patients with obesity present additional risk factors for macroangiopathy, and are recognised to present metabolic syndrome, insulin resistance, and typical for diabetes type 2 - polycystic ovary syndrome, or non-alcoholic fatty liver disease. The prevalence of obesity rises dramatically in adolescence of diabetic child, more often in girls. It has negative impact on metabolic control, glycaemic variability and insulin demand. The risk for microangiopathic complications increases as well. The treatment is difficult and includes not only insulinotherapy and non-pharmacological trials. Recently treatment of insulin resistance with biguanids, and treatment with typical for type 2 new diabetes drugs like GLP-1 analogues, SGLT-2 receptor inhibitors, or even cases of bariatric surgery also has been reported.

The Burden of Diabetes-Related Chronic Kidney Disease in China From 1990 to 2019.

To analyze the trends in disease burden of diabetes-related chronic kidney disease (CKD) by year, age, gender and types of diabetes in China from 1990 to 2019. Data on prevalence, deaths and disability-adjusted life years (DALYs) for diabetes-related CKD were extracted from the Global Burden of Disease (GBD) 2019 study. Analyses were performed by year, age, gender and types of diabetes. In China, the numbers of deaths and DALYs of diabetes-related CKD continuously increased but the age-standardized rates (per 100,000 population) decreased over 30 years, in which the numbers of deaths and DALYs attributable to type 1 diabetes mellitus (T1DM)-related CKD barely changed and the age-standardized rates decreased over the years and the number of deaths and DALYs attributable to type 2 diabetes mellitus (T2DM)-related CKD continuously increased, but the age-standardized rates also decreased. In 2019, 76.03 (58.24-95.61) thousand deaths and 2.13 (1.65-2.67) million DALYs were attributable to diabetes-related CKD, of which, T2DM accounted for 83.32% and 77.0% respectively, and T1DM accounted for the rest. Increasing gender disparity was seen, with males being more heavily impacted. The burden of diabetes-related CKD varied among different age groups, with the numbers of deaths and DALYs attributable to T1DM-related CKD peaking between 45 and 54 years of age and T2DM-related CKD peaking between 75 and 79 years of age and the crude rates of deaths and DALYs attributable to T1DM-related CKD peaking between 70 and 79 years of age and 40 to 54 years of age, respectively, and T2DM-related CKD peaking over 90 years of age. Among neighboring and G20 countries, the burden of diabetes-related CKD in China was relatively controlled reflected by the ranking of adjusted death and DALYs rates. The burden of diabetes-related CKD in China worsens and shows gender disparities and different age distribution. Greater efforts are needed to improve the health outcomes of these patients, especially among males.

Sodium Glucose Cotransporter-2 Inhibitor Protects Against Diabetic Neuropathy and Nephropathy in Modestly Controlled Type 2 Diabetes Follow-Up Study.

This three-year follow-up study aimed to elucidate whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) have any protection against diabetic neuropathy and nephropathy in patients with type 2 diabetes Two type 2 diabetic cohorts of 40 and 73 patients treated with or without SGLT2i along with 60 control subjects were recruited. Two diabetic cohorts matched for HbA1c levels and oral hypoglycemic agents other than SGLT2is underwent glycemic control with or without SGLT2is more than two years. The urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) every 3 months and neuropathy outcome measures and mean Z-score of 8 neurophysiological tests were determined at the baseline and endpoint. Glycemic variability, evaluated by the coefficient of variation of monthly measured HbA1c levels and casual postprandial plasma glucose (CPPG), and coefficient of variation and average of extraglycemic parameters in diabetic cohorts were determined. The glycemic variability and variability of some extraglycemic factors in SGLT2i cohort were smaller than those in non-SGLT2i cohort. However, only smaller coefficient of variation of HbA1c improved some neuropathy outcome measures, and ameliorated eGFR decline. SGLT2i improved the Z-score of neurophysiological tests. The optimized changes in the blood pressure, HDL-cholesterol and uric acid by SGLT2i led to neurological and renal protection. SGLT2i decreased the prevalence of nephropathy significantly and the prevalence of neuropathy insignificantly. Over 3 years period, SGLT2i significantly improved some neuropathy outcome measures, mean Z-score of 8 neurophysiological tests, and attenuated nephropathy in modestly controlled type 2 diabetes by reducing glycemic variability and mean nonglycemic factors of diabetic microvascular complication.

Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus A UPLC-MS-Based Untargeted Metabolomics Study.

Recurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies. We screened 553 community-based T2DM patients. T2DM with RH (DH group, We identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all RH in T2DM is accompanied by caffeine, lipolysis, phenylalanine, and cortisone metabolism abnormalities. Caffeine might be a reliable candidate biomarker and potential prevention strategy for RH, but further validation studies are needed. Chi CTR 1900026361, 2019-10-3.

Low Serum Dehydroepiandrosterone Is Associated With Diabetic Kidney Disease in Men With Type 2 Diabetes Mellitus.

The associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with diabetic kidney disease (DKD) remained unclear. Thus, this cross-sectional study aimed to explore the associations of DHEA and DHEAS with the risk of DKD in patients with T2DM. The information of 1251 patients with T2DM were included in this study. Serum DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry assays. Multivariate logistic regression analyses were used to assess the associations of DHEA and DHEAS with DKD as well as high urine albumin to creatinine ratio (ACR). In men with T2DM, the risk of DKD decreased with an increasing DHEA concentration after adjustment for traditional risk factors the fully adjusted OR (95% CI) for tertile3 vs tertile1 was 0.37 (0.19-0.70 P 0.010 for trend). Similarly, when taking high ACR as the outcome, low DHEA levels were still significantly associated with increased odds of high ACR (OR, 0.37 95% CI, 0.19-0.72 for tertile3 vs tertile1 P 0.012 for trend). The restricted cubic spline showed that the risk of DKD gradually decreased with the increment of serum DHEA levels (P-overall 0.007 P-nonlinear 0.161). DHEAS was not independently associated with the risk of DKD in men. In contrast, no significant relationships were found between DHEA and DHEAS and the risk of DKD in women (all P > 0.05). In men with T2DM, low serum DHEA levels were independently related to the risk of DKD after adjustment for traditional risk factors. Our finding highlights the potential role of DHEA in the development of DKD in men with T2DM.

Jiangtang Tongmai Prescription Reduced Diabetic Lung Injury Through SnoN and TGF-β1Smads Signaling Pathway.

By establishing a rat diabetes model in rats with intervening treatment by Jiangtang Tongmai Prescription (JTTMP), this study explored the restorative pairing effect of JTTMP on diabetic lung injury. The model of type II diabetes model was used to establish the rat diabetes model, using a high-fat diet and streptozotocin (STZ) induction. Different doses of JTTMP and metformin were administered as a therapeutic to intervene, and blood was collected to assess the blood glucose level of each group of rats. HE (Hematoxylin and eosin (HE) staining was performed to detect the morphological changes in rat lung tissue and enzyme-linked immunoassay ELISA was used to detect and quantify the expression of interleukin (IL)-6, TNF tumor necrosis factor-ɑa, and IL-1β in serum and the lung tissue of each group of rats. The level expression of TGF-β1 transforming growth factor (TGF)-β1), SnoN (transcriptional co-repressor Ski-N terminal (SnoN), Smad2, Smad3, Smad7, and other signaling pathway proteins were assessed by Western blot. In comparison with the normal control (NC) group, rats in the diabetes model (DM) group lost weight and showed significantly increased blood sugar levels. The levels of TGF-β1 and Smad23 were increased in the DM group but Smad7 decreased. After 8 weeks of JTTMP intervention, the level of TGF-β1 and Smad23 decreased but Smad7 increased, blood sugar decreased significantly and the expression of inflammatory factors in lung tissue decreased. Therefore, JTTMP may activate SnoN and the downstream TGF-β1Smads signaling pathway to repair diabetic lung injury, which suggests its application has potential for future clinical treatment of diabetes with lung injury.

Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy.

Glucagon-like peptide 1 (GLP-1) receptor agonists have demonstrated strong glycemic control. However, few studies have investigated the effects of switching from insulin to GLP-1 receptor agonists. We aimed to investigate, using real-world data, whether switching to dulaglutide improves glycemic control in patients with type 2 diabetes mellitus (T2D) inadequately controlled with conventional insulin treatment. We retrospectively evaluated 138 patients with T2D who were switched from insulin to dulaglutide therapy. We excluded 20 patients who dropped out during the follow-up period. The participants were divided into two groups according to whether they resumed insulin treatment at 6 months after switching to a GLP-1 receptor agonist (group I) or not (group II). A multiple logistic regression analysis was performed to evaluate the parameters associated with the risk of resuming insulin after replacement with dulaglutide. Of 118 patients initiated on the GLP-1 receptor agonist, 62 (53%) resumed insulin treatment (group I), and 53 (47%) continued with GLP-1 receptor agonists or switched to oral anti-hypoglycemic agents (group II). Older age, a higher insulin dose, and lower postprandial glucose levels while switching to the GLP-1 receptor agonist were associated with failure to switch to the GLP-1 receptor agonist from insulin. A considerable proportion of patients with T2D inadequately controlled with insulin treatment successfully switched to the GLP-1 receptor agonist. Younger age, a lower dose of insulin, and a higher baseline postprandial glucose level may be significant predictors of successful switching from insulin to GLP-1 receptor agonist therapy.

Association Between High-Sensitivity C-Reactive Protein and Diabetic Kidney Disease in Patients With Type 2 Diabetes Mellitus.

High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker. This study aimed to identify the correlation between hs-CRP levels and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This cross-sectional and observational study included 927 patients with T2DM. We collected the data of patients based on their medical data, including sociodemographic characteristics, concomitant diseases, laboratory results, and medical therapy. Multivariate logistic regression analysis was conducted to assess the relationship between hs-CRP levels and DKD. A restricted cubic spline (RCS) was used to assess the correlation of hs-CRP levels on a continuous scale with the DKD. In total, 927 patients were recruited in our study. The median age of the recruited patients was 55 years, and there were 346 female patients and 581 male patients. The hs-CRP levels were evidently higher in patients with DKD than those without DKD. After adjusting for age, sex, diastolic blood pressure, systolic blood pressure, body mass index, neck circumference, waist circumference, hypertension, duration of diabetes, common carotid artery plaque, fasting plasma glucose, glycated hemoglobin, hemoglobin, erythrocyte, leukocyte, γ-glutamyl transferase, albumin, urea nitrogen, uric acid and triglyceride, a significant increase in the odds ratios (ORs) for DKD in the fourth hs-CRP quartile compared with the first quartile was observed (P value for trend 0.003), and the ORs (95% confidence intervals) in the fourth quartile of hs-CRP were 1.968 (1.244-3.114) for DKD compared to the first quartile.. Moreover, the RCS curves presented a positive association between hs-CRP and DKD in total subjects, male subjects and female subjects, respectively. The results of our study indicated that hs-CRP levels were significantly and positively correlated with the presence of DKD, which may provide predictive and diagnostic values in clinical practice.

Kidney outcomes associated with sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists A real-world population-based analysis.

Kidney benefits have been demonstrated for both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) compared with placebo in patients with type 2 diabetes. This study aimed to compare the impacts of SGLT2i and GLP1RA on the trend of estimated glomerular filtration rate (eGFR) and other kidney outcomes. Using a real-world population-based database, the Hong Kong Hospital Authority (HA) database, of patients with type 2 diabetes between January 2008 and December 2020, patients started on SGLT2i were compared with those started on GLP1RA, with one-to-one propensity-score matching. Primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), incident macroalbuminuria and kidney-related mortality. Secondary outcome was the rate of eGFR decline. A total of 2551 SGLT2i and 2551 GLP1RA new users were analyzed. At baseline, mean age was 56·2 years, with mean eGFR 78·0 mLmin1·73m Our results suggest that SGLT2i might be superior to GLP1RA in reducing kidney outcomes among patients with type 2 diabetes. Future trials are needed to corroborate our findings. None.

Liver Fibrosis in Primary Sjögrens Syndrome.

Primary Sjögren syndrome (pSS) is a systemic autoimmune epithelitis, potentially affecting salivary epithelium, biliary epithelium, and hepatocytes. Common immunological mechanisms might cause clinically silent liver inflammation, and combined with non-alcoholic fatty liver disease (NAFLD), liver fibrosis (LF) may occur. No studies have explored the occurrence of LF in the context of NAFLD among pSS patients. Consecutive pSS patients from the rheumatology outpatient clinic of the Department of Pathophysiology and individuals evaluated in the hepatology outpatient clinic for possible NAFLD serving as comparators underwent transient elastography (TE) to assess LF and liver steatosis (LS). All participants had no overt chronic liver disease. Clinical, demographic, and laboratory data were collected from all participants at the time of TE. Fifty-two pSS patients and 198 comparators were included in the study. The median age (range) of pSS and comparators was 62.5 (30-81) and 55 (19-86) years, respectively. Both groups had similar prevalence regarding type 2 diabetes mellitus, hyperlipidemia, and similar body mass index (BMI). Patients with pSS had less frequently high LS (S2, S3) (27% vs. 62%, Liver fibrosis among pSS patients is most likely not attributed to the disease

Nonalcoholic Fatty Liver Disease An Emerging Modern-Day Risk Factor for Cardiovascular Disease.

Nonalcoholic fatty liver disease (NAFLD), also named metabolic dysfunction-associated fatty liver disease (MAFLD), is a progressive disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is a clinically silent disease leading to multiple extra-hepatic complicationscomorbidities. It is an independent risk factor for cardiovascular disease (CVD), increasing susceptibility to hypertension, atherosclerosis, arrhythmia, myocardial dysfunction, cardiac valve deformation, and venous thrombosis through putative mechanisms including systemic inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and altered lipid metabolism. Eventually, it increases the CVD prevalence, incident, and fatality, contributing to a huge health care burden. In fact, CVD is becoming the leading cause of mortality among patients with NAFLD. Other cardiometabolic risk factors coexisting with NAFLD may also accelerate the synergistic development of CVD, which warrants assessment targeting hypertension, diabetes mellitus (DM), obesity, and dyslipidemia to be an integral part of NAFLD care. Monitoring metabolic biomarkers (glucose, glycosylated hemoglobin HbA1c, insulin, lipids, and lipoproteins), cardiovascular (CV) risk scores (American College of CardiologyAmerican Heart Association ACCAHA or Framingham), and subclinical atherosclerosis (coronary artery calcification CAC, carotid intima-media thickness CIMT, and carotid plaque) are recommended for risk prediction and reduction. There is no universally accepted treatment for NAFLD, and lifestyle changes with weight loss of at least 10% are the mainstay of management. Combination therapy of ezetimibe and statins have a cardioprotective effect and help reduce liver fat. Despite being an emerging risk factor for CVD and its rapidly increasing pattern affecting a quarter of the global population, NAFLD remains overlooked and undetected, unlike the other traditional risk factors. Hence, we conducted a comprehensive narrative review to shed more light on the importance of screening CVD in NAFLD patients. PubMed indexed relevant articles published from 2002 to 2022 (20 years) were searched in April 2022 using medical subject headings (MeSH) as nonalcoholic fatty liver disease Mesh AND cardiovascular diseases Mesh. Evidence from 40 observational studies, three clinical trials, one case series, 45 narrative reviews, four systematic reviews and meta-analyses, three systematic reviews, and one meta-analysis were summarized on the epidemiologic data, pathophysiologic mechanisms, clinical features, diagnostic modalities, overlapping management, perceived challenges and health literacy regarding the CVD risk attributed to NAFLD.

Engineering Functional Vascularized Beige Adipose Tissue from Microvascular Fragments of Models of Healthy and Type II Diabetes Conditions.

Engineered beige adipose tissues could be used for screening therapeutic strategies or as a direct treatment for obesity and metabolic disease. Microvascular fragments are vessel structures that can be directly isolated from adipose tissue and may contain cells capable of differentiation into thermogenic, or beige, adipocytes. In this study, culture conditions were investigated to engineer three-dimensional, vascularized functional beige adipose tissue using microvascular fragments isolated from both healthy animals and a model of type II diabetes (T2D). Vascularized beige adipose tissues were engineered and exhibited increased expression of beige adipose markers, enhanced function, and improved cellular respiration. While microvascular fragments isolated from both lean and diabetic models were able to generate functional tissues, differences were observed in regard to vessel assembly and tissue function. This study introduces an approach that could be employed to engineer vascularized beige adipose tissues from a single, potentially autologous source of cells.

Polyethylene Glycol Loxenatide Injection (GLP-1) Protects Vascular Endothelial Cell Function in Middle-Aged and Elderly Patients With Type 2 Diabetes by Regulating Gut Microbiota.

Quality of Life in University Students with Diabetes Distress Type 1 and Type 2 of Diabetes Differences.

This study constitutes a preliminary trial to clarify the relationship between quality of life (QoL) and diabetes distress (DD in patients with diabetes mellitus (DM) by comparing patients with type 1 and type 2 diabetes. A cross-sectional study of university students with diabetes (type 1 and type 2) diabetes. One hundred sixty-six students were assigned to participate in this study. A self-report questionnaire on demographic and clinical parameters was taken. Rating worries and anxieties related to diabetes were evaluated using the diabetes distress scale-17, and quality of life was tested using SF-36 v2. No significant differences were observed in the level of DD according to sociodemographics in type 1 DM (T1DM) and type 2 DM (T2DM) ( University students with diabetes showed a high level of DD with no significant differences between both types of diabetes this consequently affects all components of QoL. Psychological support is the better choice for those students for better health and future career.

Identification of Flavonoid C-Glycosides as Promising Antidiabetics Targeting Protein Tyrosine Phosphatase 1B.

Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of the insulin signaling pathway, has gained attention as a validated druggable target in the management of type 2 diabetes mellitus (T2DM). The lack of clinically approved PTP1B inhibitors has continued to prompt research in plant-derived therapeutics possibly due to their relatively lesser toxicity profiles. Flavonoid C-glycosides are one of the plant-derived metabolites gaining increased relevance as antidiabetic agents, but their possible mechanism of action remains largely unknown. This study investigates the antidiabetic potential of flavonoid C-glycosides against PTP1B

Crescentic Glomerulonephritis and Membranous Nephropathy A Rare Overlap.

Membranous nephropathy (MN) is a disease that affects the basement membrane of the glomeruli of the kidney resulting in proteinuria. The concurrent incidence of vasculitic glomerulonephritis and MN in the same patient is unusual. Herein, we report a case with this unusual combination. Our patient is a 53-year-old Hispanic male with a medical history of tobacco use, type 2 diabetes mellitus, and hypertension who presented with hematuria and was found to have nephrotic range proteinuria and renal impairment. Blood workup revealed positive ANCA serology, which led to a renal biopsy that showed crescentic vasculitis in addition to membranous nephropathy. The patient was started on intermittent hemodialysis (HD) and treated initially with intravenous (IV) pulse steroids subsequently, oral prednisolone and IV cyclophosphamide were initiated. The patient remained HD dependent at the time of discharge with the resolution of hematuria. A follow-up with an outpatient nephrology clinic was arranged. Membranous nephropathy complicated by crescentic glomerulonephritis has a more aggressive clinical course and decline in renal function compared to MN alone which can lead to initiating renal replacement therapy. However, immunosuppressive drugs can result in significant improvement of renal function if started early enough.

Changes in target ability of nanoparticles due to protein corona composition and disease state.

Many studies have shown the influence of protein corona (PC) on the active targeting capability of ligand-modified nanoparticles however, the influence of clinical status on PC composition and targeting capacity is rarely discussed. In this study, when transferrin-modified PEGylated polystyrene nanoparticles (Tf-PNs) is intravenously injected into mice with non-small cell lung cancer (NSCLC) comorbid with type 2 diabetes mellitus (T2DM), more Tf-PNs accumulated in the tumor tissue than in those of NSCLC model mice. This indicated that PC derived from different states of disease changed the active targeting ability of Tf-PNs. To explain the occurrence of this phenomenon, our analysis of PC from different disease states revealed that Tf (transferrin) modification had no significant effect on the formation of PC, and that the PC from the NSCLC comorbid with T2DM model contained more proteins like fibrin and clusterin. This work demonstrates the impacts of comorbidity, such as with T2DM, on the active targeting capability of ligand-modified nanoparticles, and the results promote the application of nanoparticles for precision medicine.

Massive hypertriglyceridemia associated with paclitaxel a case report.

This report describes a patient who developed massive hypertriglyceridemia (12,488 mgdL or 141 mmolL) during paclitaxel and carboplatin adjuvant chemotherapy for high grade serous fallopian tube carcinoma. Paclitaxel was thought to be the causative agent and she had normal triglyceride levels following a change to carboplatin and gemcitabine. To our knowledge, this is the highest reported triglyceride level associated with paclitaxel. Measurement of serum lipids should be considered in individuals receiving taxane chemotherapy, especially in those with type 2 diabetes mellitus or a history of dyslipidemia.

Analysis of Risk Factors of Coronary Heart Disease and Its Correlation with Inflammatory Factors in Patients with Type 2 Diabetes Mellitus.

In this paper, we propose a new method to analyze the risk factors of coronary heart disease (CHD) and their correlation with inflammatory factors in patients with type 2 diabetes mellitus (T2DM). To verify and implement this idea, we have selected a total of 165 patients with T2DM treated in our hospital from March 2019 to October 2021 that were divided into CHD group (

Pancreas Transplantation in Black, Asian and Minority Ethnic Patients-Single Centre Experience in the UK.

Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas transplantation in the UK has not been reported and hence we aimed to investigate our cohort. A retrospective analysis of all pancreas transplant recipients (

From lessons on the long-term effects of the preimplantation environment on later health to a modified ART-DOHaD animal model.

At its earliest stages, mammalian embryonic development is apparently simple but vulnerable. The environment during the preimplantation period, which only lasts a couple of days, has been implicated in adult health, extending to such early stages the concept of the developmental origin of health and disease (DOHaD). In this review, we first provide a brief history of assisted reproductive technology (ART) focusing on in vitro culture and its outcomes during subsequent development mainly in mice and humans. Further, we introduce the MEM mouse, a novel type 2 diabetes mouse model generated by in vitro culture of preimplantation embryos in alpha minimum essential medium (αMEM). The association between ART and its long-term effects has been carefully examined for its application in human infertility treatment. The MEM mouse develops steatohepatitis and kidney disease with diabetes into adulthood. The close association between the environment of preimplantation and health in postnatal life is being clarified. The approach by which severe mouse phenotypes are successfully induced by manipulating the environment of preimplantation embryos could provide new chronic disease animal models, which we call modified ART-DOHaD animal models. This will also offer insights into the mechanisms underlying their long-term effects.

Efficacy and Safety of Ultra-Rapid Lispro in Younger and Older Patients with Type 2 Diabetes Randomized Double-Blind PRONTO-T2D Study.

Ultra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior to lispro (Humalog PRONTO-T2D was a phase 3, 26-week, double-blind, treat-to-target study in people with type 2 diabetes. In this sub-group analysis, we compared URLi to lispro on the change from baseline in HbA1c and rate of level 2 hypoglycemia (< 54 mgdl) in patients aged < 65 (N 406) and ≥ 65 years (N 267). At baseline, patients < 65 versus ≥ 65 years had mean age of 54.9 versus 69.2 years and duration of diabetes 14.6 versus 19.4 years. Mean HbA1c at screening and randomization was 8.35 and 7.34%, respectively, in patients < 65 years, and 8.21 and 7.23%, respectively, in patients ≥ 65 years. At endpoint, mean HbA1c with URLi versus lispro was 6.92 versus 6.90%, respectively, in patients < 65 years and 6.89 versus 6.79%, respectively, in patients ≥ 65 years. URLi significantly reduced 1- and 2-h PPG excursions with a standardized meal test in both age groups between-treatment differences at 1-h postmeal for younger and older patients was - 9.8 and - 15.1 mgdl, respectively and at 2-h postmeal, - 18.7 and - 15.1 mgdl, respectively, all p < 0.05. Severe and nocturnal hypoglycemia were similar between groups. The relative rate (URLiHumalog) of level 2 hypoglycemia was lower in older versus younger patients, with a significant treatment-by-age interaction observed. No differential treatment effects were noted for insulin dose, weight, and fasting and maximum glucose after the meal test. URLi, in a basal-bolus regimen, resulted in endpoint HbA1c < 7% and significantly lower PPG excursions compared to lispro in both age groups, with reduced level 2 hypoglycemia in older versus younger patients. ClinicalTrials.gov, NCT03214380.

Risk of Type 2 Diabetes Among Individuals with Excess Weight Weight Trajectory Effects.

Increased risk of type 2 diabetes mellitus (T2D) among individuals with overweight or obesity is well-established however, questions remain about the temporal dynamics of weight change (gain or loss) on the natural course of T2D in this at-risk population. Existing epidemiologic evidence is limited to studies that discretely sample and assess excess weight and T2D risk at different ages with limited follow-up, yet changes in weight may have time-varying and possibly non-linear effects on T2D risk. Predicting the impact of weight change on the risk of T2D is key to informing primary prevention. We critically review the relationship between weight change, trajectory groups (i.e., distinct weight change patterns), and T2D risk among individuals with excess weight in recently published T2D prevention randomized controlled trials (RCTs) and longitudinal cohort studies. Overall, weight trajectory groups have been shown to differ by age of onset, sex, and patterns of insulin resistance or beta-cell function biomarkers. Lifestyle (diet and physical activity), pharmacological, and surgical interventions can modify an individuals weight trajectory. Adolescence is a critical etiologically relevant window during which onset of excess weight may be associated with higher risk of T2D. Changes in insulin resistance and beta-cell function biomarkers are distinct but related correlates of weight trajectory groups that evolve contemporaneously over time. These multi-trajectory markers are differentially associated with T2D risk. T2D risk may differ by the age of onset and duration of excess body weight, and the type of weight loss intervention. A better understanding of the changes in weight, insulin sensitivity, and beta-cell function as distinct but related correlates of T2D risk that evolve contemporaneously over time has important implications for designing and targeting primary prevention efforts.

Screening for type 2 diabetes and hypertension in seafarers medical examinations.

The aims of the study are 1) to replace the urine glucose test for diabetes with more than 50% false negatives, with an accurate screening for type 2 diabetes and hypertension in the mandatory biannual fit-for-duty medical examinations of seafarers 2) to produce data driven Green Ship health pro-motion in the ships. A new health promotion and disease prevention public health intervention programme integrated in the fit-for-duty medical examinations for seafarers is being developed. The lack of an accurate diagnosis of type 2 diabetes is replaced by accurate HbA1c andor fasting glucose tests and the test for hypertension in various disease stages is based on the International Associations Guidelines. A Green Ship health promotion programme is proposed for all on board, not only for diseased crew members. A protocol for an accurate biannual screening for diabetes and hypertension is presented. Educational programmes for medical doctors and seafarers on the management of hypertension and diabetes on board will be developed. Presuming that all crew members are potentially on their way to be pre-diseased or are diseased, the Green Ship health promotion programme is implemented for the whole crew. The International Labour Organization and the National Maritime Authorities are prompted to revise the International and the National Guidelines for Seafarers Medical Examinations, respectively. Con-certed actions are requested to implement public health promotion projects in shipping. Maritime medical doctors are prompted to use health dialogues and to report the clinical data in the Excel file. Sustainability is obtained by complying with the Sustainable Development Goals (3, 4, 8, 10, and 17).

Evaluation of central corneal epithelial thickness with anterior segment OCT in patients with type 2 diabetes mellitus.

This study aimed to evaluate the central corneal thickness (CCT) and central corneal epithelial thickness (CCET) in patients with Type 2 diabetes mellitus (DM), and the effect of the duration of diabetes, the degree of diabetic retinopathy (DR), and HbA1c level. CCT and CCET values of 72 patients diagnosed with type 2 DM and 72 healthy individuals were measured by anterior segment optical coherence tomography. The eye tear function was evaluated with the Tear Break-up Time test (TBUT) and the Schirmer test. From the results of fundus examination, the diabetic patients were grouped as those without DR, non-proliferative DR, and proliferative DR. The disease duration and the HbA1c levels were recorded. In the diabetic patients, the mean CCT was determined to be thicker (p 0.025), the CCET was thinner (p 0.003), and the TBUT and Schirmer values were lower (p <0.001, p <0.001, respectively). The duration of diabetes and the HbA1c level was not found to have any statistically significant effect on these parameters (p >0.05). The presence of retinopathy had no significant effect on CCT, TBUT, and Schirmer values. The CCET was determined to be thinner in patients with retinopathy (p <0.001). As the corneal epithelial thickness is reduced in patients with advanced diabetic retinopathy, corneal epithelial pathologies can be seen more often. Therefore, early and effective treatment can be started by taking into consideration the complications which may develop associated with the corneal epithelium following surgical procedures, especially those applied to the cornea.

Potential mechanisms underlying the association between type II diabetes mellitus and cognitive dysfunction in rats a link between miRNA-21 and Resveratrols neuroprotective action.

Cognitive impairment is considered as a typical feature of neurodegenerative diseases in diabetes mellitus (DM). However, the exact link between cognitive dysfunction and diabetes mellitus is still vague. This study aims to investigate some of the mechanisms underlying cognitive impairment that associates diabetes mellitus and insulin resistance. We investigated the role of resveratrol as well on cognitive function in experimentally induced type 2 diabetes highlighting on its influence on the expression of brain miRNA 21. Resveratrol is a naturally occurring, biologically active compound that has numerous significant impacts on the body. Type 2 diabetes mellitus was induced by high fat diet followed a single dose of streptozotocin. Diabetic rats were treated with resveratrol for four weeks. Rats were sacrificed after neurobehavioral testing. Hippocampal tissues were used to assess expression of miRNA 21, GSK and oxidative stress markers. Serum samples were obtained to determine glucose levels, lipid profile and insulin levels. Hippocampal and serum AGEs were measured as well and HOMA IR was calculated. We detected memory impairment and disturbed insulin signaling in diabetic rats. These derangements were reversed by resveratrol treatment partially due to increased expression of miRNA-21. Our study pins the role of miRNA-21 in modulating brain insulin signaling and hence alleviating cognitive dysfunction accompanying diabetes mellitus.

What have we missed because of COVID-19 Missed diagnoses and delayed follow-ups. SESPAS Report 2022.

The COVID-19 pandemic and the associated public health emergency have affected patients and health services in non-COVID-19 pathologies. Several studies have shown its dissociation from health services, with a decrease in emergency department visits, in hospital admissions for non-COVID-19 pathologies, as well as in the reported weekly incidence of acute illnesses and new diagnoses in primary care. In parallel, the pandemic has had direct and indirect effects on people with chronic diseases the difficulties in accessing health services, the interruption of care, the saturation of the system itself and its reorientation towards non-face-to-face formats has reduced the capacity to prevent or control chronic diseases. All this has also had an impact on the different areas of peoples lives, creating new social and economic difficulties, or aggravating those that existed before the pandemic. All these circumstances have changed with each epidemic wave. We present a review of the most relevant studies that have been analyzing this problem and incorporate as a case study the results of a retrospective observational study carried out in Primary Care in the Madrid Health Service, which provides health coverage to a population of more than 6 million people, and whose objective was to analyze the loss of new diagnoses in the most prevalent pathologies such as common mental health problems, cardiovascular and cerebrovascular diseases, type 2 diabetes, chronic obstructive pulmonary disease, and breast and colon tumors, in the first and second waves. Annual incidence rates with their confidence interval were calculated for each pathology and the monthly frequency of new codes recorded between 1012020 and 12312020 was compared with the monthly mean of observed counts for the same months between 2016 and 2019. The annual incidence rate for all processes studied decreased in 2020 except for anxiety disorders. Regarding the recovery of lost diagnoses, heart failure is the only diagnosis showing an above-average recovery after the first wave. To return to pre-pandemic levels of diagnosis and follow-up of non-COVID-19 pathology, the healthcare system must reorganize and contemplate specific actions for the groups at highest risk. La pandemia de COVID-19 y la emergencia de salud pública asociada han afectado a loslas pacientes y a los servicios de salud en lo que respecta a las patologías no relacionadas con la COVID-19. Diversos estudios han evidenciado su desvinculación con los servicios sanitarios, con disminución de las consultas a los servicios de urgencias, de los ingresos hospitalarios de patologías no COVID-19, así como de la incidencia semanal notificada de enfermedades agudas y nuevos diagnósticos en atención primaria. Paralelamente, la pandemia ha tenido efectos directos e indirectos en las personas con enfermedades crónicas las dificultades de acceso a los servicios sanitarios, la interrupción de la atención, la saturación del propio sistema y su reorientación hacia formatos no presenciales ha reducido la capacidad de prevenir o controlar las enfermedades crónicas, impactando además en los diferentes ámbitos de la vida de las personas, creando nuevas dificultades sociales y económicas, o agravando las preexistentes antes de la pandemia. Todas estas circunstancias se han ido modificando con cada una de las olas epidémicas. Se presenta una revisión de los estudios más relevantes que han ido analizando este problema y se incorporan como estudio de caso los resultados de un estudio observacional retrospectivo realizado en atención primaria en Madrid, que da cobertura sanitaria a una población de más de 6 millones de personas, y cuyo objetivo ha sido analizar la pérdida de nuevos diagnósticos en las patologías más prevalentes, como los problemas comunes de salud mental, enfermedades cardiovasculares y cerebrovasculares, diabetes tipo 2, enfermedad pulmonar obstructiva crónica y tumores de mama y de colon, en la primera y la segunda olas. Se calcularon las tasas de incidencia anual con su intervalo de confianza para cada patología y se comparó la frecuencia mensual de los nuevos códigos registrados entre el 1 de enero y el 31 de diciembre de 2020 con la media mensual de los recuentos observados para los mismos meses en 2016-2019. La tasa de incidencia anual para todos los procesos estudiados disminuyó en 2020, excepto para los trastornos de ansiedad. En relación con la recuperación de los diagnósticos perdidos, la insuficiencia cardiaca es el único diagnóstico que presenta una recuperación por encima de la media después de la primera ola. Para volver a los niveles prepandémicos de diagnóstico y seguimiento de la patología no COVID-19, el sistema sanitario debe reorganizarse y contemplar acciones específicas para los grupos de mayor riesgo.

The genetics of bipolar disorder with obesity and type 2 diabetes.

Bipolar disorder (BD) presents with high obesity and type 2 diabetes (T2D) and pathophysiological and phenomenological abnormalities shared with cardiometabolic disorders. Genomic studies may help define if they share genetic liability. This selective review of BD with obesity and T2D will focus on genomic studies, stress their current limitations and guide future steps in developing the field. We searched electronic databases (PubMed, Scopus) until December 2021 to identify genome-wide association studies, polygenic risk score analyses, and functional genomics of BD accounting for body mass index (BMI), obesity, or T2D. The first genome-wide association studies (GWAS) of BD accounting for obesity found a promising genome-wide association in an intronic gene variant of TCF7L2 that was further replicated. Polygenic risk scores of obesity and T2D have also been associated with BD, yet, no genetic correlations have been demonstrated. Finally, human-induced stem cell studies of the intronic variant in TCF7L2 show a potential biological impact of the products of this genetic variant in BD risk. The narrative nature of this review. Findings from BD GWAS accounting for obesity and their functional testing, have prompted potential biological insights. Yet, BD, obesity, and T2D display high phenotypic, genetic, and population-related heterogeneity, limiting our ability to detect genetic associations. Further studies should refine cardiometabolic phenotypes, test gene-environmental interactions and add population diversity.

Meteorin-like protein (Metrnl) A metabolic syndrome biomarker and an exercise mediator.

Metrnl is a secreted protein able to activate different intracellular signaling pathways in adipocytes, macrophages, myocytes and cardiomyocytes with physiological effects of the browning of white adipose tissue (BWT), insulin sensitivity, inflammation inhibition, skeletal muscle regeneration and heart protection. Shown to be regulated by obesity, diabetes, caloric restriction, weight loss and heart diseases, Metrnl is definitely involved in metabolic turbulences, and may play roles in metabolic syndrome (MetS). However, due to the conflicting data yielded, Metrnl is still far from clinical application as a diagnostic andor a therapeutic agent or even a therapeutic target in MetS-related diseases such as type 2 diabetes (T2D) and obesity. Nevertheless, blood Metrnl levels as well as Metrnl as a cardiokine have been reported to play cardioprotective roles against heart diseases. Considering the established metabolic and anti-inflammatory hallmarks, exercise-induced Metrnl (as a myokine) is regarded as an exercise mediator in improving obesity-induced complications such as insulin resistance, T2D and inflammation. Besides, due to its healing role in muscle damage, Metrnl is also a potential therapeutic candidate to enhance regeneration with ageing or other inflammatory myopathies like Duchenne muscular dystrophy (DMD). Therefore, there are still many exercise-related questions unanswered on Metrnl, such as Metrnl-mediated fat browning in humans, exercise effects on heart Metrnl production and secretion and the effects of other exercise-induced skeletal muscle stressors like hypoxia and oxidative in Metrnl production other than exercise-induced muscle damage.

The influence of high-fat and high-sucrose feeding regimes on organ weight, body weight, and serum concentration of bioelements in rats.

Obesity is one of the most common diseases of civilization, and approximately 13 % of the worlds adult population is obese. Obesity is defined as excessive accumulation of fat in the human body, which leads to adverse health effects such as metabolic syndrome, type 2 diabetes, and fatty liver disease (e.g., nonalcoholic liver disease). The development of obesity is accompanied by changes in the levels of certain bioelements such as copper and zinc. These elements may have an influence on the proper functioning of the central nervous system. Fifty-six male Wistar rats (initial weight 290-300 g) were divided into seven experimental groups. They were fed with different feeding patterns (constant versus intermittent-binge access) and exposed to different diets (high sucrose versus high fat) to analyze the factors that affect the organ weight gain (pancreas, spleen, liver, testes, and kidneys) and total body weight gain. Further, zinc and copper levels in the serum of the animals were determined. The relationship between organ and body weight and serum metal concentration was analyzed by cluster and principal component analyses. Rats with unlimited access to high fat diet (HF) and restricted intake of high sugar diet (for 2-hours daily-HSB and every second day-IHSB) have elevated body weight in comparison to the control. However, the heaviest organ weights were recorded in the HSB rats compared to the control group (pancreas, 14 % spleen, 9 % kidneys, 5 % and liver, 3 %). On the other hand, an average 20 % decrease in zinc concentration was observed in rats fed with high-fat diet compared to the control. Moreover, an 18 % decrease in copper levels was observed in rats that had periodic access to high-fat diet every 2 h daily and for 2 h every other day compared to the control. Both the high-sucrose and high-fat diets had an influence on body and organ weights. This study demonstrates an association between the different types of diet and the parameters investigated (body and organ weights and concentration of serum bioelements).

Health-related quality of life of people with type 2 diabetes and its associated factors at a tertiary care clinic in Ningbo, China A cross-sectional study.

The burden of type 2 diabetes (T2DM) in China is increasing, with potential impacts on the health-related quality of life (HRQoL) of those who develop the disease. Context-specific assessment of HRQoL and its associated factors informs the development of contextually appropriate interventions to improve HRQoL. This study aimed to determine the HRQoL and its associated factors in people with T2DM at a tertiary care clinic in Ningbo, China. A cross-sectional survey was undertaken among 406 people with T2DM in 2020-21. The primary outcome was HRQoL measured using EQ VAS and EQ-5D index from the EQ-5D-3L questionnaire. Multivariable regression analysis was used to determine the factors associated with HRQoL scores. The mean (± standard deviation) EQ VAS score was 68.7 (13.8). Median (interquartile range) EQ-5D index was 1 (0.027). Prevalence of problems in HRQoL domains was as follows paindiscomfort (15.7%), anxietydepression (13.3%), mobility (5.4%), self-care (3.5%) and managing usual activities (5.2%). The ≥60 years age group had a mean EQ VAS score 8.7 points higher (95% CI 3.4, 13.9 p < .001) than the 18-39 years age group. Those with T2DM >10 years had a mean EQ VAS score 8.6 points lower than those with a duration <1 year (-12.8, -4.4 p .001). A T2DM duration >10 years was associated with a reduction in the EQ-5D index of 0.029 (-0.041, -0.016 p < .001) compared with a duration <1 year. Depressionanxiety and paindiscomfort are important domains of reduced HRQoL for this population. A longer duration of T2DM is associated with reduced HRQoL scores, including both EQ VAS and EQ-5D index. Increasing age may be counterintuitively associated with an increase in EQ VAS score in this population, potentially reflecting a paradox of aging process. Future work should focus on developing, evaluating and implementing interventions to improve HRQoL in T2DM, such as strategies to manage pain and mental health conditions.

Mortality and morbidity risk prediction for older former smokers based on a score of smoking history evidence from UK Biobank and ESTHER cohorts.

Rapid population ageing has raised the proportion of older former smokers considerably, but a comprehensive assessment tool of former smoking-related health risks is absent. We utilised the large-scale data of UK Biobank and ESTHER study to build a former smoking score (FSS) for older former smokers using three major former smoking traits pack-years, smoking duration and time since smoking cessation. UK Biobank and ESTHER study are two cohorts of older adults with 502,528 and 9,940 participants from the UK and Germany, respectively. Smoking history and covariates were retrieved from the self-administrated questionnaires and mortality and morbidity data were obtained through regular linkages to hospital records. We constructed the FSS based on the 94,446 former smokers of UK Biobank by retrieving the averaged effect estimates of each trait with a 100-time random sampling. This score was robustly associated with higher risks of mortality and incidence of major smoking-related diseases, outperforming each trait. In the validation panel of 2,683 former smokers from ESTHER study, the FSS was highly predictive of mortality and morbidities. Particularly, compared with the 1st quartile of the FSS group, the 4th quartile group had 114.1, 104.5 and 158.9% higher risks of all-cause, CVD and cancer mortality, respectively, and 41.9, 31.9, 52.4 and 831.3% higher risks of incident CVD, type 2 diabetes, any cancers and lung cancer, respectively. Our study demonstrates the large potential of refined risk assessment of former smokers by more comprehensive consideration of the major traits of former smoking.

Association of Obesity and Serum Gamma Glutamyl Transferase with Impaired Fasting Glucose in Adults at a Tertiary Level Hospital of Bangladesh.

Obesity is a worldwide health concern due to its rising tendency both in developing and developed countries. Obesity is known to be associated with a number of disorders including type 2 diabetes mellitus, hypertension and cardiovascular diseases. Gamma glutamyl transferase (GGT) is synthesized in liver. GGT is considered as an oxidative stress marker. Serum GGT is increased in patients with cardiovascular diseases and diabetes mellitus (DM). Impaired fasting glucose (IFG) is a risk factor for cardiovascular diseases. The aim of this study was to find out the association of obesity and serum GGT with IFG. This cross-sectional analytical study was conducted in the Biochemistry department of Sir Salimullah Medical College, Dhaka from March 2018 to February 2019. The ages of the subjects were 25-55 years. The study subjects were 120 and were divided into two groups. The groups were Normal fasting glucose (NFG) group and IFG group according to WHO diagnostic criteria. Body mass index (BMI) was used as a measure of general obesity and waist circumference (WC) and waist-hip ratio (WHR) were used as measures of abdominal or central obesity. OGTT was performed from collected blood. GGT and lipid profile were measured from serum. In IFG group, BMI, WC, WHR and GGT levels were significantly elevated (p<0.01) than NFG group i.e. BMI (22.70±1.35 vs. 28.37±2.33kgm²), WC (79.96±5.31 vs. 93.42±4.21cm), WHR (0.92±0.06 vs. 0.97±0.07), and GGT (24.19±8.41 vs. 67.23±14.40UL). Fasting Plasma Glucose (FPG) level were significantly higher (p<0.01) in obese group than over weight and normal BMI groups 4.70±0.08, 5.30±1.3 and 6.50±0.3 respectively. FPG were higher in male and female obese group than normal WC group (4.8±1.1 vs. 6.3±0.60mmolL) and (4.4±0.7 vs. 6.2±0.80mmolL). Odds Ratio (OR) and (95% CI) for IFG were 6.53 and 21.0 with BMI tertile 2(23.1- 27.5kgm²) and tertile 3(≥27.5kgm²) where T₁ (<23.0kgm²) was considered as reference category. OR for IFG were 4.1 and 20.25 with GGT tertile 2(24.0-42.0) UL and tertile 3(>42.0) UL where T₁ (<24.0) UL was considered as reference category. Multiple regression analysis shows positive correlation of FPG with BMI, WC, WHR and GGT.

Regular combined training and vitamins modulated the apoptosis process in diabetic rats Bioinformatics analysis of heart failures differential genes expression network correlated with anti-apoptotic process.

The apoptosis process could impose significantly by hyperglycemia. According to in silico language processing and high throughput raw data analysis, we recognized hub molecular mechanisms involved in the pathogenesis of diabetic hearts and suggested a new pharmaceutical approach for declining myocardial programed cell death. Fifty male Sprague-Dawley rats were classified into five groups healthy rats as control, diabetic rats, diabetic combined resistanceendurance training, diabetic rats which consumed supplementation vitamins E and C, and the combined supplementation and training. Here, we calculated changes in gene expression based on artificial intelligence methods and evaluated gene expression in apoptotic influencing combined training and antioxidants vitamins consumption in heart injured models by streptozotocin via Real-Time PCR. Moreover, we assessed the binding affinity of the 3D structure of small molecules on macromolecule SIRT3 to a new compound pharmaceutical suggesting the decline in cell death program. The computational intelligence surveys revealed that the apoptosis process was a remarkable pathomechanism in the abnormality function of heart tissue in diabetic conditions. Furthermore, we showed that synchronizing antioxidant vitamin consumption and regular combined training could significantly decrease irreversible myocardial cell death in diabetic myocardiopathy. Hence, levels of antiapoptotic mRNA were modified in the combined trainingvitamin consumption group compared with other classifications. We found that regular combined exercise and vitamin consumption could reverse the apoptosis process to enhance the survival of cardiac muscle cells in diabetes conditions. PRACTICAL APPLICATIONS Machine learning and system biology indicated that the apoptosis process is a vital pathomechanism of hyperglycemia-induced heart failure. Sirt3FasBcl-2Cycs and Bax, as a critical network of apoptosis, play an essential role in heart failure induced by hyperglycemia. Moreover, Type 2 diabetes and obesity increase the risk of heart failure by increasing high blood sugar levels. We calculated the binding power of the vitamins E and C on SIRT3 protein based on the drug software. In addition, this study assessed that regular combined training and vitamin consumption had an antiapoptotic effect. Also, our data might improve the hyperglycemia state.

Quality outcome of diabetes care during COVID-19 pandemic a primary care cohort study.

Management of diabetes care can be affected by COVID-19 pandemic control measures. This study aimed to determine the impact of the pandemic, during 17.03.2020-16.03.2021, on quality outcomes of diabetes care in general practice in Switzerland. In this retrospective cohort study, diabetes mellitus patients (≥ 18 years) with at least one consultation at a general practitioner, during 17.03.2018-16.03.2019 (cohort 1) and 17.03.2019-16.03.2020 (cohort 2) were included and followed-up for two years. Quality indicators and outcomes of diabetes care, at patient and practitioner level, were compared before and during the pandemic. Logistic regression was performed to identify patients risk factors for dropout from follow-up. Data from 191 practices, 23,903 patients, cohort 1 and 25,092 patients, cohort 2, were analyzed. The fraction of patients lost to follow-up, attributable to the pandemic, was 28% (95% confidence interval 25%, 30%). During the pandemic, compared to the previous year, regular measurement of weight, HbA1c, blood pressure and serum creatinine were less frequent and less patients per practitioner reached HbA1c and blood pressure target outcomes. Factors associated with continuity of care during the pandemic were patient age 41-80 years, longer diabetes duration, diagnosis of hypertension or dyslipidemia, influenza vaccination during the last year. Risk factors for dropout were age > 80 and receiving only insulin as anti-diabetic medication. A considerable quality reduction in diabetes mellitus care could be observed during the pandemic. Though the most vulnerable patients were not the most affected by the pandemic, key factors that might reduce dropout from follow-up were identified.

Excess dietary fructose consumption promotes metabolic dysfunction thereby increasing the risk of obesity, type 2 diabetes, non-alcoholic steatohepatitis (NASH), and related comorbidities. PF-06835919, a first-in-class ketohexokinase (KHK) inhibitor, showed reversal of such metabolic disorders in preclinical models and clinical studies, and is under clinical development for the potential treatment of NASH. In this study, we evaluated the transport and metabolic pathways of PF-06835919 disposition and assessed pharmacokinetics in preclinical models. PF-06835919 showed active uptake in cultured primary human hepatocytes, and substrate activity to organic anion transporter (OAT)2 and organic anion transporting-polypeptide (OATP)1B1 in transfected cells. SLC-phenotyping studies in human hepatocytes suggested contribution of passive uptake, OAT2- and OATP1B-mediated transport to the overall uptake to be about 15%, 60% and 25%, respectively. PF-06835919 showed low intrinsic metabolic clearance in vitro, and was found to be metabolized via both oxidative pathways (58%) and acyl glucuronidation (42%) by CYP3A, CYP2C8, CYP2C9 and UGT2B7. Following intravenous dosing, PF-06835919 showed low clearance (0.4-1.3 mLminkg) and volume of distribution (0.17-0.38 Lkg) in rat, dog and monkey. Human oral pharmacokinetics are predicted within 20% error when considering transporter-enzyme interplay in a PBPK model. Finally, unbound liver-to-plasma ratio (Kp

Statins were not associated with hepatocellular carcinoma after controlling for time-varying confounders in patients with diabetes.

We examined the association between statin use and hepatocellular carcinoma (HCC) incidence in patients with diabetes using marginal structural models (MSMs) estimated by inverse probability weight (IPW), which adjusts for time-varying confounders that are also mediators, and we compared the results with conventional regression methods. This retrospective cohort study included 245,122 patients with type 2 diabetes who were new users of lipid-lowering drugs identified using the claims data of a universal health insurance program. Statin exposure was time-updated every three months during the follow-up period. Stabilized IPW was calculated and accounted for chronic liver diseases considering as time-dependent confounders affected by past statin exposure. Over a median follow-up of 5.2 years, 1,694 patients developed HCC. In the conventional regression analysis, the hazard ratio of HCC associated with statin use was 0.88 (95% confidence interval CI 0.79-0.97) after adjusting for baseline covariates and 0.97 (95% CI 0.87-1.08) after additionally adjusting for time-varying covariates. The hazard ratio increased to 1.11 (95% CI 0.94-1.31) using the MSM approach. Statin use was not associated with the risk of developing HCC in patients with diabetes. Our findings highlight the importance of controlling time-varying confounders in observational studies.

Positive regulation of endothelial Tom70 by metformin as a new mechanism against cardiac microvascular injury in diabetes.

Microvascular protection is the main mechanism of metformin against diabetic complications. Cardiac microvascular endothelial cells (CMECs) are the basic component of cardiac microvessels, and they suffer from oxidative stress and mitochondrial dysfunction under type 2 diabetes mellitus (T2DM). Translocase of the outer mitochondrial membrane 70 (Tom70) improves mitochondrial dysfunction, but its role in the hearts of T2DM patients remains unclear. The purpose of this study was to demonstrate the protective effect of metformin on diabetic cardiac microvascular injury and to identify the role of Tom70 in this effect. T2DM mice were established by multiple intraperitoneal injections of low-dose streptozotocin and 12-week high-fat feeding. CMECs were isolated and cultured with normal glucose (NG), high glucose (HG), and HG plus high fat (HG-HF) media. The results indicated that long-term metformin treatment partly reversed cardiovascular complication and mitigated cardiac microvascular injury in T2DM. In addition, exposure to HG-HF led to CMEC damage, aggravated oxidative stress, aggravated mitochondrial dysfunction, and reduced mitochondrial Tom70 expression, whereas upregulation of Tom70 significantly ameliorated these injuries. Furthermore, metformin treatment promoted Tom70 expression and effectively reversed CMEC injury induced by HG-HF. However, all of these effects were interrupted after Tom70 was knocked down. In conclusion, T2DM damages microvascular integrity by activating a cycle of decreased Tom70 expression, mitochondrial dysfunction, and reactive oxygen species (ROS) overload in CMECs. However, metformin suppresses oxidative stress, relieves mitochondrial dysfunction, and promotes the expression of Tom70, ultimately ameliorating diabetic microvascular injury and heart complications.

Determinants of blood acylcarnitine concentrations in healthy individuals of the European Prospective Investigation into Cancer and Nutrition.

Circulating levels of acylcarnitines (ACs) have been associated with the risk of various diseases such as cancer and type 2 diabetes. Diet and lifestyle factors have been shown to influence AC concentrations but a better understanding of their biological, lifestyle and metabolic determinants is needed. Circulating ACs were measured in blood by targeted (15 ACs) and untargeted metabolomics (50 ACs) in 7770 and 395 healthy participants of the European Prospective Investigation into Cancer and Nutrition (EPIC), respectively. Associations with biological and lifestyle characteristics, dietary patterns, self-reported intake of individual foods, estimated intake of carnitine and fatty acids, and fatty acids in plasma phospholipid fraction and amino acids in blood were assessed. Age, sex and fasting status were associated with the largest proportion of AC variability (partial-r up to 0.19, 0.18 and 0.16, respectively). Some AC species of medium or long-chain fatty acid moiety were associated with the corresponding fatty acids in plasma (partial-r 0.24) or with intake of specific foods such as dairy foods containing the same fatty acid. ACs of short-chain fatty acid moiety (propionylcarnitine and valerylcarnitine) were moderately associated with concentrations of branched-chain amino acids (partial-r 0.5). Intake of most other foods and of carnitine showed little association with AC levels. Our results show that determinants of ACs in blood vary according to their fatty acid moiety, and that their concentrations are related to age, sex, diet, and fasting status. Knowledge on their potential determinants may help interpret associations of ACs with disease risk and inform on potential dietary and lifestyle factors that might be modified for disease prevention.

Using nuclear magnetic resonance urine metabolomics to develop a prediction model of early stages of renal disease in subjects with type 2 diabetes.

Type 2 diabetes mellitus (DM2) is a multimorbidity, long-term condition, and one of the worldwide leading causes of chronic kidney disease (CKD) -a silent disease, usually detected when non-reversible renal damage have already occurred. New strategies and more effective laboratory methods are needed for more opportune diagnosis of DM2-CKD. This study comprises clinical parameters and nuclear magnetic resonance (NMR)-based urine metabolomics data from 60 individuals (20-65 years old, 67.7% females), sorted in 5 experimental groups (healthy subjects diabetic patients without any clinical sign of CKD and patients with mild, moderate, and severe DM2-CKD), according to KDIGO. DM2-CKD produces a continuous variation of the urine metabolome, characterized by an increasedecrement of a group of metabolites that can be used to monitor CKD progression (trigonelline, hippurate, phenylalanine, glycolate, dimethylamine, alanine, 2-hydroxybutyrate, lactate, and citrate). NMR profiles were used to obtain a statistical model, based on partial least squares analysis (PLS-DA) to discriminate among groups. The PLS-DA model yielded good validation parameters (sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve (ROC) plot 0.692, 0.778 and 0.912, respectively) and, thus, it can differentiate between subjects with DM2-CKD in early stages, from subjects with a mild or severe condition. This metabolic signature exhibits a molecular variation associated to DM2-CKD, and data suggests it can be used to predict risk of DM2-CKD in patients without clinical signs of renal disease, offering a new alternative to current diagnosis methods.

The GHIGF-1 Axis Is Associated With Intrahepatic Lipid Content and Hepatocellular Damage in OverweightObesity.

Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GHIGF-1 axis has not been well characterized in NAFLD. We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. This cross-sectional study included 102 adults (43% women age 19-67 BMI ≥ 25 kgm2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy NAFLD was defined by ≥ 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LCMS). There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8 ± 13.3% vs 2.9 ± 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 ± 6.3 vs 15.4 ± 11.2 ngmL, P 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (P 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD.

Analysis of clinical phenotypes of neuropathic symptoms in patients with type 2 diabetes A multicenter study.

We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms, and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients. This multicenter study analyzed epidemiological data and sensory symptoms of 649 patients with DPN. Cluster analysis was carried out to identify subgroups of patients with characteristic symptom profiles. Factor analysis was carried out to investigate the symptom patterns of the clustered groups of DPN patients. Three clusters of patients with DPN were identified severe symptoms with decreased quality of life (cluster 1, n 119, 18.3%), predominantly insensate symptoms with relatively good quality of life (cluster 2, n 318, 49.0%), and moderate pain intensity and decreased quality of life (cluster 3, n 204, 31.4%). The frequency of symptoms on each item of the Michigan Neuropathy Screening Instrument questionnaire showed a similar distribution according to pain intensities along with the three clusters. Our study supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach. Based on a multicenter study, we identified three clusters of patients with DPN. Our research supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach.

Patient-reported outcome measures for assessing health-related quality of life in people with type 2 diabetes A systematic review.

Patient-Reported Outcome Measures (PROMs) are important tools to assess outcomes relevant to patients, with Health-Related Quality Of Life (HRQOL) as an important construct to be measured. Many different HRQOL PROMs are used in the type 2 diabetes field, however a complete overview of these PROMs is currently lacking. We therefore aimed to systematically describe and classify the content of all PROMs that have specifically been developed or validated to measure (aspects of) HRQOL in people with type 2 diabetes. A literature search was performed in PubMed and EMBASE until 31 December 2021. Studies on the development or validation of a PROM measuring HRQOL, or aspects of HRQOL, in people with type 2 diabetes were included. Title and abstract and full-text screening were conducted by two independent researchers and data extraction was performed independently by one of the researchers. Data were extracted on language in which the PROM was developed, target population, construct(s) being measured, names of (sub)scales and number of items per (sub)scale. In addition, all PROMs and subscales were classified according to specific aspects of HRQOL based on the Wilson Cleary model (symptom status, functional status, general health perceptions) to aid researchers in PROM selection. In total 220 studies were identified that developed or validated PROMs that measure (aspects of) HRQOL in people with type 2 diabetes. Of the 116 unique HRQOL PROMs, 91 (of the subscales) measured symptom status, 60 measured functional status and 26 measured general health perceptions. In addition, 16 of the PROMs (subscales) measured global quality of life. 61 of the 116 PROMs (subscales) also include characteristics of the individual (e.g. aspects of personality, coping) or environment (e.g. social or financial support) and patient-reported experience measures (PREMs, e.g. measure of a patients perception of their personal experience of the healthcare they have received, e.g. treatment satisfaction), which are not part of the HRQOL construct. Only 9 of the 116 PROMs measure all aspects of HRQOL based on the Wilson Cleary model. Finally, 8 of the 116 PROMs stating to measure HRQOL, measured no HRQOL construct. In conclusion, a large number of PROMs are available for people with type 2 diabetes, which intend to measure (aspects of) HRQOL. These PROMs measure a large variety of (sub)constructs, which are not all HRQOL constructs, with a small amount of PROMs not measuring HRQOL at all. There is a need for consensus on which aspects of HRQOL should be measured in people with type 2 diabetes and which PROMs to use in research and daily practice. PROSPERO CRD42017071012. COMET database httpwww.comet-initiative.orgstudiesdetails956 .

Effect of Diabetes on Morbidity and Mortality in Patients With Acromegaly.

Diabetes is a major risk factor for cardiovascular disease and death but its effect on outcomes in acromegaly is unknown. This work aimed to study whether diabetes affects morbidity and mortality in patients with acromegaly. A nationwide (Sweden), observational, matched-cohort study was conducted. Patients diagnosed with acromegaly between 1987 and 2020 were identified in the Swedish National Patient Registry and those with concomitant type 2 diabetes in the National Diabetes Registry and Drug Registry. The risk of overall mortality, and cardiovascular mortality and morbidity were estimated using Cox regression. The study included 254 patients with acromegaly and concomitant type 2 diabetes (ACRO-DM group) and 532 without diabetes (ACRO group). Mean (SD) age at baseline was 62.6 (11.4) and 60.0 (12.1) years (P .004) and the mean (SD) duration of acromegaly was 6.8 (8.1) and 6.0 (6.2) years (P .098) in the ACRO-DM and ACRO groups, respectively. Overall mean follow-up was 9.2 years. The unadjusted overall mortality rate per 1000 person-years was 35.1 (95% CI, 27.2-44.7) and 20.1 (95% CI, 16.5-24.3) in the respective groups. The hazard ratio (HR) for overall mortality adjusted for multiple confounders was 1.58 (95% CI, 1.12-2.23) in the ACRO-DM group compared with the ACRO group. Cardiovascular mortality (HR 2.11 95% CI, 1.09-4.10) and morbidity (HR 1.49 95% CI, 1.21-1.82) were also increased in the ACRO-DM group. The presence of diabetes in patients with acromegaly was associated with increased overall mortality as well as increased cardiovascular mortality and morbidity.

Prevalence of obstructive sleep apnea syndrome in hospitalized patients with type 2 diabetes in Beijing, China.

To estimate the prevalence, and patient clinical and demographic profile, as well as risk factors associated with obstructive sleep apnea syndrome (OSAS) in hospitalized patients with type 2 diabetes mellitus in Beijing, China. Hospitalized adult patients with type 2 diabetes mellitus were consecutively screened and invited for an overnight polysomnography from four hospitals in Beijing, China, from May 2016 to February 2017. We used the American Academy of Sleep Medicine 2012 polysomnography recording techniques and scoring criteria to identify the type of apnea and the severity of OSAS. The χ A total of 735 patients were found eligible for the study, of whom 309 patients completed the overnight polysomnography. The mean age of the patients was 58.2 ± 10.9 years, and most (67.3%) were men. The prevalence of overall (apnea hypopnea index ≥5h), moderate-to-severe (apnea hypopnea index ≥15h) and severe (apnea hypopnea index ≥30h) OSAS was 66.3% (95% confidence interval 60.8-71.6%), 35.6% (95% confidence interval 30.3-41.2%) and 16.5% (95% confidence interval 12.5-21.1%), respectively. Central and mixed apnea contributed 12% to all sleep-disordered breathing. With the aggravation of OSAS, the combined prevalence for central, mixed and obstructive apnea increased from 57% to 70%. We found OSAS to be associated with older age, obesity, self-reported snoring and apnea, and diabetes complications. Guidelines on screening and treatment of OSAS among hospitalized patients with diabetes are needed to direct the routine practice for diabetes endocrinologists for optimal clinical care of such patients.

hsacirc0115355 promotes pancreatic β-cell function in patients with type 2 diabetes through the miR-145SIRT1 axis.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease closely related to obesity, a growing global health problem. T2DM is characterized by decreased islet beta-cell mass and impaired insulin release from these cells, and this dysfunction is exacerbated by hyperglycemia (glucolipotoxicity). Circular RNAs (circRNAs) are abnormally expressed and play a regulatory role in T2DM. This study aimed to evaluate the function and molecular mechanism of hsacirc0115355 in the progression of T2DM. The regulatory effect of hsacirc0115355 on INS-1 cell function was assessed under glucolipotoxicity by MTT, flow cytometry analysis, and insulin secretion assay. Dual-luciferase experiments revealed a direct interaction of hsacirc0115355 with miR-145 and miR-145 with SIRT1. Furthermore, the regulatory role of the hsacirc0115355miR-145SIRT1 axis was verified by examining the function of INS-1. In this study, hsacirc0115355 was significantly underexpressed in both patients with T2DM and INS-1 cell lines. This study thus showed that hsacirc0115355 inhibits the occurrence and development of T2DM by regulating the expression of SIRT1 by adsorbing miR-145. The underexpression hsacirc0115355 is also a potential novel diagnostic marker and therapeutic target for T2DM.

Cognitive behavioral therapy delivered via digital mobile application for the treatment of type 2 diabetes Rationale, design, and baseline characteristics of a randomized, controlled trial.

The prevalence of type 2 diabetes (T2D) continues to rise in the United States and worldwide. Cognitive behavioral therapy (CBT) has been shown to improve glycemic control in patients with T2D, but broad implementation has been limited by inherent access and resource constraints. Digital therapeutics have the potential to overcome these obstacles. To describe the rationale and design of a trial evaluating the efficacy and safety of a digital therapeutic providing CBT to improve glycemic control in adults with T2D. This randomized, controlled, multicenter, Phase 3 trial evaluates the hypothesis that BT-001, an investigational digital therapeutic intended to help patients with T2D improve their glycemic control, on top of standard of care therapy, will lower hemoglobin A1c (HbA1c) compared to a control app across a broad range of patients in a real-world setting. The study is designed to provide evidence to support FDA review of this device as a digital therapeutic. The intervention is provided within the digital application (app) and includes no person-to-person coaching. The primary endpoint is the difference in HbA1c change from baseline to 90 days for BT-001-allocated subjects compared with those assigned to the control app. Safety assessment includes adverse events and adverse device effects. The study incorporates pragmatic features including entirely remote conduct with at-home visits for physical measures and blood sample collection. This randomized, controlled trial evaluates a cognitive behavioral intervention delivered via smartphone app which has the potential to provide a scalable treatment option for patients with T2D.

StatPearls

Obesity refers to abnormal or excess body weight (mainly fat) concerning height. It is a growing health problem in the United States as well as around the globe with a significant economic burden. More than a third of individuals in the USA have a body mass index (BMI) of over 30kgm2, and the cost for obesity has risen to $147 billion annually. It is also associated with various comorbidities, which include type 2 diabetes mellitus, heart diseases, stroke, obstructive sleep apnea, Hypogonadism, and premature death. According to the Center for Disease Control and Prevention (2015-2016 data), approximately 93.3 million US adults were obese. A similar trend is on the rise in many other western countries.

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Pioglitazone is a drug used in the management of type 2 diabetes mellitus. Pioglitazone is the third marketed thiazolidinedione group of oral antidiabetics, the first is troglitazone which is no longer available due to hepatotoxicity, and the second is rosiglitazone, still on the market. This activity reviews the indications, mechanism of action, and contraindications for pioglitazone in managing type 2 diabetes mellitus. This activity highlights the mechanism of action, adverse effect profile, monitoring, and relevant interactions.

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Rosiglitazone is a medication used in the management and treatment of type 2 diabetes mellitus. It is in the thiazolidinediones class of medications. This activity reviews the indications, actions, and contraindications for rosiglitazone as a valuable agent in the management of diabetes type 2. This activity will highlight rosiglitazone requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results and prevent complications.

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Insulin resistance is identified as an impaired biologic response to insulin stimulation of target tissues, primarily the liver, muscle, and adipose tissue. Insulin resistance impairs glucose disposal, resulting in a compensatory increase in beta-cell insulin production and hyperinsulinemia. The metabolic consequences of insulin resistance can result in hyperglycemia, hypertension, dyslipidemia, visceral adiposity, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, and a prothrombic state. Progression of insulin resistance can lead to metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus. Insulin resistance is primarily an acquired condition related to excess body fat, though genetic causes are identified as well. The clinical definition of insulin resistance remains elusive as there is not a generally accepted test for insulin resistance. Clinically, insulin resistance is recognized via the metabolic consequences associated with insulin resistance as described in metabolic syndrome and insulin resistance syndrome. The gold standard for measurement of insulin resistance is the hyperinsulinemic-euglycemic glucose clamp technique. This is a research technique with limited clinical applicability however, there are a number of clinically useful surrogate measures of insulin resistance, including HOMA-IR, HOMA2, QUICKI, serum triglyceride, and triglycerideHDL ratio. In addition, several measures assess insulin resistance based on serum glucose andor insulin response to a glucose challenge. The predominate consequence of insulin resistance is type 2 diabetes (T2DM). Insulin resistance is thought to precede the development of T2DM by 10 to 15 years. The development of insulin resistance typically results in a compensatory increase in endogenous insulin production. Elevated levels of endogenous insulin, an anabolic hormone, is associated with insulin resistance and results in weight gain which, in turn, exacerbates insulin resistance. This vicious cycle continues until pancreatic beta-cell activity can no longer adequately meet the insulin demand created by insulin resistance, resulting in hyperglycemia. With continued mismatch between insulin demand and insulin production, glycemic levels rise to levels consistent with T2DM. Resistance to exogenous insulin has also been described. An arbitrary but clinically useful benchmark considers patients requiring greater than 1 unitkilogramday of exogenous insulin to maintain glycemic control insulin resistant. Patients requiring greater than 200 units of exogenous insulin per day are considered severely insulin resistant. In addition to T2DM, the spectrum of disease associated with insulin resistance includes obesity, cardiovascular disease, nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary syndrome(PCOS). These are all of great consequence in the United States with a tremendous burden being placed on the healthcare system to treat the direct and indirect conditions associated with insulin resistance. The microvascular complications of diabetes (neuropathy, retinopathy, and nephropathy), as well as the associated macrovascular complications (coronary artery disease CAD, cerebral-vascular disease, and peripheral artery disease PAD), consume the lions share of the healthcare dollar. Lifestyle modification should be the primary focus for the treatment of insulin resistance. Nutritional intervention with calorie reduction and avoidance of carbohydrates that stimulate excessive insulin demand are a cornerstone to treatment. Physical activity helps to increase energy expenditure and improve muscle insulin sensitivity. Medications also can improve insulin response and reduce insulin demand.

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Bloom syndrome, also called Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema, is a rare genodermatosis characterized by genomic instability and predisposition to the development of a variety of cancers. Bloom syndrome is caused by mutations in the

The Effects of Adding Semaglutide to High Daily Dose Insulin Regimens in Patients With Type 2 Diabetes.

Escalating doses of insulin required with progression of type 2 diabetes may lead to weight gain. Weight loss associated with semaglutide may be beneficial. However, data on the use of semaglutide in patients requiring high daily doses of insulin are currently lacking. The purpose of this project was to evaluate the impact of semaglutide on total daily dose (TDD) of insulin when initiated in patients with type 2 diabetes mellitus (T2DM) on high daily doses of insulin. Secondary objectives assessed included changes in weight, body mass index (BMI), blood pressure, heart rate, and diabetes and blood pressure medications. This IRB exempt retrospective medical record review included patients with T2DM prescribed semaglutide and at least 100 units TDD of insulin between January 1, 2019, and December 31, 2019. Of the 72 patients included, the TDD of insulin decreased from baseline to 6 months (183 ± 98 units and 143 ± 99 units, Improvement in glycemic control occurred despite reductions in TDD of insulin. Improvements in A1c and body weight were clinically significant. This analysis adds to existing literature supporting the use of GLP-1 RAs in patients on high daily doses of insulin.

Milestones of progression in myotonic dystrophy type 1 and type 2.

Disease progression in myotonic dystrophy (DM) is marked by milestone events when functional thresholds are crossed. DM type 2 (DM2) is considered less severe than DM type 1 (DM1), but it is unknown whether this applies uniformly to all features. We compared the age-dependent risk for milestone events in DM1 and DM2 and tested for associations with age of onset and sex. We studied a large cohort of adult participants in a national registry of DM1 and DM2. Using annual surveys from participants, we ascertained milestone events for motor involvement (use of cane, walker, ankle brace, wheelchair, or ventilatory device), systemic involvement (diabetes, pacemaker, cancer), loss of employment due to DM, and death. Mean follow-up of registry participants (929 DM1 and 222 DM2 patients) was 7 years. Disability and motor milestones occurred at earlier ages in DM1 than in DM2. In contrast, the risk of diabetes was higher and tended to occur earlier in DM2 (hazard ratio HR, 0.56 P ≤ .001). In DM1, the milestone events tended to occur earlier, and life expectancy was reduced, when symptoms began at younger ages. In DM1, men were at greater risk for disability (HR, 1.34 P ≤ .01), use of ankle braces (HR, 1.41 P .02), and diabetes (HR, 2.2 P ≤ .0001), whereas women were at greater risk for needing walkers (HR, 0.68 P .001) or malignancy (HR, 0.66 P ≤ .01). Milestone events recorded through registries can be used to assess long-term impact of DM in large cohorts. Except for diabetes, the age-related risk of milestone events is greater in DM1 than in DM2.

Alterations in circulating levels of vitamin D binding protein, total and bioavailability of vitamin D in diabetic retinopathy patients.

This study aimed to investigate the association between circulating levels of vitamin D binding protein (VDBP) and its genotypes and diabetic retinopathy risk. This case-control study recruited 154 patients with type 2 diabetes mellitus 62 with diabetic retinopathy (DR) and 92 without DR and diabetic nephropathy (DN). Circulating levels of 25-hydroxyvitamin D3 and VDBP levels were measured in the patients. The genotype and phenotype of VDBP were evaluated based on two common VDBP variations rs7041 and rs4588. Serum levels of VDBP were significantly lower in patients with DR than in patients without DR andor DN (Ln-VDBP (μgml) 6.14 ± 0.92 vs. 6.73 ± 1.45, p 0.001) even after adjustment for age, sex, body mass index, disease duration, estimated glomerular filtration rate (eGFR), HbA1C, insulin therapy profile, and serum levels of 25(OH)D. The distribution of VDBP phenotypes and genotypes in the two studied groups were nearly the same, and the distribution was similar to that of the general population. In this study, we found the association between lower circulating levels of VDBP and risk of DR. However, the precise mechanism linking these two remains unknown. Further and more in-depth research is needed to find out the underlying causes of the relationship.

Using an optimized generative model to infer the progression of complications in type 2 diabetes patients.

People live a long time in pre-diabetesearly diabetes without a formal diagnosis or management. Heterogeneity of progression coupled with deficiencies in electronic health records related to incomplete data, discrete events, and irregular event intervals make identification of pre-diabetes and critical points of diabetes progression challenging. We utilized longitudinal electronic health records of 9298 patients with type 2 diabetes or prediabetes from 2005 to 2016 from a large regional healthcare delivery network in China. We optimized a generative Markov-Bayesian-based model to generate 5000 synthetic illness trajectories. The synthetic data were manually reviewed by endocrinologists. We build an optimized generative progression model for type 2 diabetes using anchor information to reduce the number of parameters learning in the third layer of the model from Formula see text to Formula see text, where Formula see text is the number of clinical findings, Formula see text is the number of complications, Formula see text is the number of anchors. Based on this model, we infer the relationships between progression stages, the onset of complication categories, and the associated diagnoses during the whole progression of type 2 diabetes using electronic health records. Our findings indicate that 55.3% of single complications and 31.8% of complication patterns could be predicted early and managed appropriately to potentially delay (as it is a progressive disease) or prevented (by lifestyle modifications that keep patient from developingtriggering diabetes in the first place). The full type 2 diabetes patient trajectories generated by the chronic disease progression model can counter a lack of real-world evidence of desired longitudinal timeframe while facilitating population health management.