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Are we there yet Increasing use of cardioprotective antihyperglycemic agents in patients with T2D and CVD or CV risk in the United States.

To report on the use of antihyperglycemic agents (AHAs) by age (i.e. <65, ≥65 years) in patients with type 2 diabetes (T2D) and cardiovascular disease (CVD) or cardiovascular risk (CV risk) factors in the United States. Patients with T2D and CVD (CVD cohort) or T2D and an additional CV risk factor without pre-existing CVD (CV risk cohort) were identified from 2015 to 2019 in a claims database. Patients were followed from their first observed CVD diagnosis or CV risk factor for each year they were continuously enrolled or until occurrence of a CVD diagnosis (CV risk cohort only). Classes of AHAs received were reported by year, cohort, and age group. From 2015 to 2019, the percentage of patients <65 years on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) increased (CVD 9-17%, CV risk 9-17%) and was approximately twice that of those ≥65 years (CVD 4-8%, CV risk 4-8%) the percentage of patients <65 years on sodium-glucose cotransporter-2 (SGLT2) inhibitors increased (CVD 11-16%, CV risk 11-17%) and was approximately triple that of those ≥65 years (CVD 3-6%, CV risk 4-7%). The use of GLP-1 RAs and SGLT2 inhibitors increased during the study period however, most patients did not receive these medications. Patients aged ≥65 years were particularly disadvantaged.

ABCC8-related maturity-onset diabetes of the young Clinical features and genetic analysis of one case.

To confirm the diagnosis of a 13-year-old adolescent with familial diabetes and further examine his genetic pathogeny. Clinical data were collected, and genetic examination was performed. PolyPhen-2 and Mutation Taster were used to predict the deleterious effects of the variant. Clustal Omega software was used to confirm the conservation of amino acid substitutions. To examine changes in the expression of proteins, recombinant vectors were constructed, and the expression of wild-type and variant target genes was detected through quantitative polymerase chain reaction. Furthermore, the wild-type and variant eukaryotic recombinant vectors were treated with a ubiquitin degradation inhibitor (MG132) and a lysosomal degradation pathway inhibitor (CQ, 3-mA). The expression of target proteins was detected through Western blot analysis. The patient had hyperglycaemia (27 mmolL), a high HbA1c level (13.1%), a decreased C-peptide level (0.63 ngml) and no diabetes antibodies. The patient had a family history of diabetes. The novel variation of ABCC8 c.2477G>A was detected in the proband and his relatives. The mutation was predicted to be harmful. Changes in the protein structure were observed. The ABCC8 c.2477G >A variant resulted in an increase in ABCC8 expression. Furthermore, changes in the expression of the ABCC8 variant was observed after 3-MA treatment, especially after treatment with MG132. At the follow-up, the patients glucose level was normal without drug therapy for more than 2 years until until he started taking Trelagliptin Succinate to control hyperglycemia within the recent 6 months. The diagnosis of maturity-onset diabetes of the young (MODY)12 was confirmed in our patient. The ABCC8 variant inhibited both ubiquitination and autophagy lysosome degradation pathways, especially the ubiquitination degradation pathway.

Loss of Lipocalin 10 Exacerbates Diabetes-Induced Cardiomyopathy

Metabolic disorders (i.e., hyperglycemia, hyperlipidemia, and hyperinsulinemia) cause increased secretion of inflammatory cytokineschemokines, leading to gradual loss of cardiac resident macrophage population and increased accumulation of inflammatory monocytesmacrophages in the heart. Such self-perpetuating effect may contribute to the development of cardiomyopathy during diabetes. Recent meta-analysis data reveal that lipocalin 10 (Lcn10) is significantly downregulated in cardiac tissue of patients with heart failure but is increased in the blood of septic patients. However, the functional role of Lcn10 in cardiac inflammation triggered by metabolic disorders has never been investigated. In this study, we demonstrate that the expression of Lcn10 in macrophages was significantly decreased under multiple metabolic stress conditions. Furthermore, Lcn10-null macrophages exhibited pro-inflammatory phenotype in response to inflammation stimuli. Next, using a global Lcn10-knockout (KO) mouse model to induce type-2 diabetes (T2D), we observed that loss of Lcn10 promoted more pro-inflammatory macrophage infiltration into the heart, compared to controls, leading to aggravated insulin resistance and impaired cardiac function. Similarly, adoptive transfer of Lcn10-KO bone marrow cells into X-ray irradiated mice displayed higher ratio of pro-anti-inflammatory macrophages in the heart and worsened cardiac function than those mice received wild-type (WT) bone marrows upon T2D conditions. Mechanistically, RNA-sequencing analysis showed that Nr4a1, a nuclear receptor known to have potent anti-inflammatory effects, is involved in Lcn10-mediated macrophage activation. Indeed, we found that nuclear translocation of Nr4a1 was disrupted in Lcn10-KO macrophages upon stimulation with LPS IFNγ. Accordingly, treatment with Cytosporone B (CsnB), an agonist of Nr4a1, attenuated the pro-inflammatory response in Lcn10-null macrophages and partially improved cardiac function in Lcn10-KO diabetic mice. Together, these findings indicate that loss of Lcn10 skews macrophage polarization to pro-inflammatory phenotype and aggravates cardiac dysfunction during type-2 diabetes through the disruption of Nr4a1-mediated anti-inflammatory signaling pathway in macrophages. Therefore, reduction of Lcn10 expression observed in diabetic macrophages may be responsible for the pathogenesis of diabetes-induced cardiac dysfunction. It suggests that Lcn10 might be a potential therapeutic factor for diabetic heart failure.

Association Between Serum Aminotransferases and Risk of New-Onset Cardiometabolic Disease in a Healthy Chinese Population A Cohort Study.

This study aimed to investigate the association between serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and incident metabolic disease in a cohort of community-based older Chinese people. Five thousand healthy Gaohang residents who attended community health checks at the Shanghai East Hospital in 2013 were recruited. Biological, biochemical, and lifestyle variables were collected. The cohort was followed for new-onset metabolic disease in 2014 and 2017, with a final study population of 3,123 (63%) after follow-up. The study outcome included type-2 diabetes mellitus and metabolic syndrome. Baseline AST and ALT were associated with incident type-2 diabetes mellitus (HR 1.019, 95% CI 1.006-1.032, This study demonstrated that serum AST and ALT are associated with new-onset type-2 diabetes mellitus, independent of traditional risk factors, in a cohort of older Chinese people. These findings may contribute to disease risk stratification and management in type-2 diabetes.

Hypothalamic Estrogen Signaling and Adipose Tissue Metabolism in Energy Homeostasis.

Obesity has become a global epidemic, and it is a major risk factor for other metabolic disorders such as type 2 diabetes and cardiometabolic disease. Accumulating evidence indicates that there is sex-specific metabolic protection and disease susceptibility. For instance, in both clinical and experimental studies, males are more likely to develop obesity, insulin resistance, and diabetes. In line with this, males tend to have more visceral white adipose tissue (WAT) and less brown adipose tissue (BAT) thermogenic activity, both leading to an increased incidence of metabolic disorders. This female-specific fat distribution is partially mediated by sex hormone estrogens. Specifically, hypothalamic estrogen signaling plays a vital role in regulating WAT distribution, WAT beiging, and BAT thermogenesis. These regulatory effects on adipose tissue metabolism are primarily mediated by the activation of estrogen receptor alpha (ERα) in neurons, which interacts with hormones and adipokines such as leptin, ghrelin, and insulin. This review discusses the contribution of adipose tissue dysfunction to obesity and the role of hypothalamic estrogen signaling in preventing metabolic diseases with a particular focus on the VMH, the central regulator of energy expenditure and glucose homeostasis.

The Prevalence, Progress and Risk Factor Control of Chronic Kidney Disease in Chinese Adults With Type 2 Diabetes Mellitus in Primary Care.

This study aimed to evaluate the prevalence of chronic kidney disease (CKD) in Chinese adults with T2DM in primary care, and the association of HbA A total of 5123 patients with ≥3 measurements of estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), HbA The prevalence of CKD, impaired eGFR and albuminuria was 29.6%, 5.8% and 27.1% at baseline, with 70.4%, 20.3%, 7.0% and 2.3% of patients distributed in low, moderate, high and very high risk group. There were 3457 (67.5%), 1120 (21.8%) and 546 (10.7%) patients had CKD outcome risk stable, progressed and regressed respectively. The proportion of patients reaching targets of BP ≤ 13080 mmHg, HbA The prevalence of CKD was high with 21.8% of patients progressing to higher CKD outcome risk at FU, attention should be paid on long term and better ABC control.

The Positive Relationship Between the Low-Density Lipoprotein CholesterolApoprotein B Ratio and Bone Turnover Markers in Patients With Type 2 Diabetes.

Dyslipidemia may contribute to low bone turnover in patients with type 2 diabetes (T2D) through mediating oxidative stress and atherosclerosis. The low-density lipoprotein cholesterolapoprotein B (LDL-CApo B) ratio is a surrogate marker of small and density low-density lipoprotein cholesterol (sd-LDL-C), a most harmful group of LDL-Cs. The present study aimed to investigate the association between the LDL-CApo B ratio and bone turnover in patients with T2D. This study was a cross-sectional study enrolled patients with T2D from January 2021 to December 2021. Each participant was assessed for lipid profiles, bone turnover markers (BTMs), lumbar spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip. A total of 335 patients with T2D were enrolled in the study, and the LDL-CApo B ratio ranged from 0.78 to 4.00. Along with the LDL-CApo B ratio tertile ascending, osteocalcin (OC), C-terminal telopeptide (CTx) and N-terminal propeptide of type-I procollagen (PINP) levels gradually increased (all The LDL-CApo B ratio was significantly and positively associated with BTMs in patients with T2D. In clinical practice, more attention should be paid to the patients with T2D whose LDL-CApo B ratio is relatively low for the purpose of maintaining bone health.

Pre-transplant Type 2 Diabetes Mellitus Is Associated With Higher Graft Failure and Increased 5-Year Mortality After Heart Transplantation.

Cardiac transplant recipients often suffer from type 2 diabetes mellitus (T2DM) but its influence on graft failure and post-transplant mortality remains unknown. The aim of this study was to investigate the long-term effects of pre-transplant T2DM in patients after heart transplantation (HTX). This study included a total of 376 adult patients who received HTX at Heidelberg Heart Center between 01012000 and 01102016. HTX recipients were stratified by diagnosis of T2DM at the time of HTX. Patients with T2DM were further subdivided by hemoglobin A1c (HbA1c ≥ 7.0%). Analysis included donor and recipient data, immunosuppressive drugs, concomitant medications, post-transplant mortality, and causes of death. Five-year post-transplant mortality was further assessed by multivariate analysis (Cox regression) and Kaplan-Meier estimator. About one-third of all HTX recipients had T2DM (121 of 376 32.2%). Patients with T2DM showed an increased 5-year post-transplant mortality (41.3% versus 29.8% Pre-transplant T2DM is associated with higher graft failure and increased 5-year mortality after HTX.

The Effect of Rye-Based Foods on Postprandial Plasma Insulin Concentration The Rye Factor.

Consumption of whole grain has been associated with lower incidence of type-2 diabetes, cardiovascular disease and their risk factors including improved glycemic control. In comparison with other whole grain products, rye bread has been shown to induce lower insulin response in the postprandial phase, without affecting the glucose response. This phenomenon has been referred to as the rye factor and is being explored in this review where we summarize the findings from meal and extended meal studies including rye-based foods. Overall, results from intervention studies showed that rye-based foods vs. (wheat) control foods had positive effect on both insulin and glucose responses in the postprandial phase, rather than on insulin alone. Mechanistic studies have shown that the rye factor phenomenon might be due to slowing of the glucose uptake in the intestine. However, this has also been shown for wheat-based bread and is likely an effect of structural properties of the investigated foods rather than the rye

Association Between Serum Asprosin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus in the Community A Cross-Sectional Study.

To explore the association between serum asprosin and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) in the community. In this cross-sectional study, we retrospectively collected the clinical data of T2DM patients from a community health service center in southeastern Shanxi Province between November 2019 and July 2021. Logistic regression analysis was used to calculate the odds ratio (OR) and the 95% confidence interval (95% CI) of asprosin levels on the risk of DN. Among 498 T2DM patients included in this study, 221 had microalbuminuria, 105 had massive albuminuria, and 172 did not have any signs of nephropathy. Serum asprosin level was positively correlated with diastolic blood pressure, body mass index, triglycerides, aspartate aminotransferase, alanine aminotransferase, creatinine, ACR and albumin-to-creatinine ratio (all P < 0.05) and negatively correlated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, HbA1c and estimated glomerular filtration rate (all P < 0.05). After adjusting for covariates, increased asprosin was associated with diabetic nephropathy (all OR 2.560, 95% CI 1.1592-4.116 P < 0.001). The risk of DN significantly increases with serum asprosin levels, especially among female patients.

The Association Between Hypertriglyceridemic-Waist Phenotype and Chronic Kidney Disease in Patients with Type 2 Diabetes A Cross-Sectional METAL Study.

The aim of this study was measuring the association between the hypertriglyceridemic-waist (HTGW) phenotype and chronic kidney disease in a large type 2 diabetes population. A total of 4254 diabetic patients from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study were enrolled. The hypertriglyceridemic-waist (HTGW) phenotype was defined as the presence of an elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 mLmin1.73 m The prevalence of CKD was 29% and 35.8% in total participants and participants with HTGW phenotype, respectively. Subjects in the HTGW phenotype group were more likely to have CKD (OR 1.47, 95% CI 1.11, 1.95) compared with subjects in the normal waist circumference and normal triglycerides (NTNW) group. HTGW phenotype was both associated with the increasing risk of decreased eGFR (OR 1.31, 95% CI 1.02, 1.75) and elevated uACR (OR 1.57, 95% CI 1.18, 2.11). Furthermore, the stratified analysis showed that the strongest positive association between HTGW phenotype and CKD presence was found in the subgroup of presence of hypertension. The associations were all fully adjusted for age, sex, BMI, current smoking, current drinking and other confounding factors. Our study suggested a positive association between the HTGW phenotype and CKD in Chinese type 2 diabetes patients. Further prospective studies are needed to confirm our findings and to investigate the underlying biological mechanisms.

Synergistic effects of liver fibrosis and sarcopenia on endothelial dysfunction and arterial stiffness in patients with type 2 diabetes.

To investigate synergistic effects of liver fibrosis evaluated by FibroScan and sarcopenia on endothelial function and arterial stiffness in patients with type 2 diabetes. This cross-sectional study evaluated liver fibrosis (LF) and sarcopenia in 115 patients with type 2 diabetes. LF was assessed as the liver stiffness measurement (LSM) in transient elastography (FibroScan) and was defined as an LSM greater than or equal to 8.0 kPa. Sarcopenia was defined as a ratio of appendicula skeletal muscle mass to body mass index of<0.789 in men and<0.512 in women. Endothelial function was measured by reactive hyperemia index (RHI) with tonometry, and arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Endothelial dysfunction was defined an RHI value below 1.67, while arterial stiffness was defined a CAVI value above 9.0. Patients were divided into four groups no LF and no sarcopenia LF but no sarcopenia no LF but sarcopenia and LF and sarcopenia. The composite of endothelial dysfunction of arterial stiffness was defined as an outcome. In patients with LF, RHI was significantly lower and CAVI was significantly higher than in patients without LF. Furthermore, RHI was significantly lower in patients with sarcopenia than in those without it. Patients with both LF and sarcopenia had the lowest RHI and the highest CAVI and urinary albumin levels. Sarcopenia and HDL cholesterol were independent factor the composite of endothelial dysfunction and arterial stiffness. LF and sarcopenia are independently associated with endothelial dysfunction and arterial stiffness in patients with type 2 diabetes. Coexistence of LF and sarcopenia may synergistically lead to vascular damage and thus contribute to the high risk of cardiovascular disease in people with type 2 diabetes.

Multiparametric magnetic resonance imaging allows non-invasive functional and structural evaluation of diabetic kidney disease.

We sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD). In the cross-sectional part of this prospective observational study, 38 subjects ages 18‒79 years with type 2 diabetes and DKD estimated glomerular filtration rate (eGFR) 15‒60 mLmin1.73 m Several MRI biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4G5) mean arterial flow (MAF) was the strongest predictor (sensitivity 0.94 and 1.0, specificity 1.00 and 0.69 A comprehensive and repeatable non-contrast mpMRI protocol was developed that, as a single, non-invasive tool, allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacymode of action of therapeutic interventions in DKD.

A real-world study on SGLT2 inhibitors and diabetic kidney disease progression.

Randomized controlled trials have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, real-world data on CKD progression and the development of end-stage kidney disease (ESKD) remains scarce. Our aim was to study renal outcomes of people with diabetic kidney disease (DKD) using SGLT2is in a highly prevalent DKD population. Between 2016 and 2019 we recruited T2DM patients in the renal and diabetic clinics in a regional hospital in Singapore. Patients prescribed SGLT2is were compared with those on standard anti-diabetic and renoprotective treatment. The outcome measures were CKD progression We analysed a total of 4446 subjects 1598 were on SGLT2is. There was a significant reduction in CKD progression hazard ratio HR 0.60 95% confidence interval (CI) 0.49-0.74 with SGLT2is. The HR for eGFR ≥45 mLmin1.73 m This real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.

Lower Extremity Salvage in a Diabetic Patient With Cutaneous Mucormycosis and COVID-19 After Open Patella Fracture.

The Adaptation of Participation Scale Short Simplified Questionnaire into Indonesian Language and the Psychometric Properties in Individuals with Type 2 Diabetes Mellitus with Vestibular Dysfunction.

Type 2 diabetes mellitus (T2DM) has been reported to affect the vestibular system resulting in dizziness and vertigo complaints. This complication is known to disable the social participation. The Participation Scale Short Simplified (PSSS) has been developed to quantify the severity of social participation restrictions. The aim of this study was to translate and cross-culturally adapt the PSSS into Indonesian Bahasa (PSSS-Ina). The measurement properties of the translated version and the factors contributing to the severe participation restriction were determined. The participants comprised 55 T2DM with vestibular dysfunction (VD) in the community center for diabetes mellitus in Central Java, Indonesia. The signs of VD were confirmed by head impulse test, Dix Hallpike Test, and supine roll test. The PSSS-Ina was administered twice with a four-week interval. The physical examination was also performed to identify the contributing factors. The test-retest reliability of the PSSS Indonesian Bahasa version (PSSS-Ina) between two measurement sessions was excellent (ICC of 0.93, The Indonesian version of the PSSS-Ina demonstrated excellent comprehensibility and reliability in individuals suffering T2DM with VD. This tool is therefore helpful in identifying the participation limitation in individuals with VD.

Impact of Electronic Polarization on Preformed, β-Strand Rich Homogenous and Heterogenous Amyloid Oligomers.

Amyloids are a subset of intrinsically disordered proteins (IDPs) that self-assemble into cross-β oligomers and fibrils. The structural plasticity of amyloids leads to sampling of metastable, low-molecular-weight oligomers that contribute to cytotoxicity. Of interest are amyloid-β (Aβ) and islet amyloid polypeptide (IAPP), which are involved in the pathology of Alzheimers disease and Type 2 Diabetes Mellitus, respectively. In addition to forming homogenous oligomers and fibrils, these species have been found to cross-aggregate in heterogeneous structures. Biophysical properties, including electronic effects, that are unique or conserved between homogenous and heterogenous amyloids oligomers are thus far unexplored. Here, we simulated homogenous and heterogenous amyloid oligomers of Aβ

Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition A Case Report and Review of the Literature.

Targeted cancer therapies have revolutionized the field of oncology by selecting for specific molecular pathways, thus improving overall clinical prognosis. However, many of these targeted treatments have been reported to have adverse kidney effects, including acute kidney injury, interstitial nephritis, and glomerular disease. Furthermore, some of these targeted therapies have also been found to cause an asymptomatic rise in serum creatinine levels through inhibition of active tubular secretion. A 79-year-old woman was being followed for stage 4 A2 chronic kidney disease secondary to type 2 diabetes and longstanding hypertension. She was diagnosed with invasive mammary carcinoma and was initiated on letrozole, an aromatase inhibitor, and palbociclib, a selective cyclin-dependent kinase inhibitor, was subsequently added. Prior to the initiation of her treatments, her baseline estimated glomerular filtration rate (eGFR) fluctuated between 25 and 28 mLmin1.73 m Given that there were no clinical or other biochemical changes suggestive of worsening renal function, a serum cystatin C was measured using an immunoturbidimetric assay, which was 1.71 mgL and correlated with an eGFR of 33 mLmin1.73 m Seven months later, a repeat serum cystatin C was repeated to assess for any worsening of the patients kidney function and revealed an eGFR of 35 mLmin1.73 m This case report and literature review acknowledges the importance of using alternative methods of assessing kidney function when patients are undergoing targeted cancer therapies known to affect tubular creatinine secretion, which include cyclin-dependent kinase 46 inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, tyrosine kinase inhibitors, and mesenchymal-epithelial transition inhibitors. The use of non-creatinine-based markers of glomerular filtration rate (GFR), such as cystatin C and nuclear renal scans, will allow for more accurate estimation of kidney function in the appropriate setting, thus avoiding invasive diagnostic tests and unnecessary adjustments of treatment plans. However, certain targeted cancer therapies have also been proven to cause true kidney injury therefore, physicians must still maintain a high degree of suspicion and consider invasive investigations andor cessation or reduction of treatments when alternative measurements of kidney function do not suggest an underestimation of GFR via serum creatinine. Les thérapies ciblées contre le cancer ont révolutionné le domaine de l’oncologie en sélectionnant des voies moléculaires spécifiques, ce qui améliore le pronostic clinique global. Il a toutefois été rapporté que plusieurs de ces traitements ciblés entraînent des effets indésirables sur les reins, notamment l’insuffisance rénale aiguë, la néphrite interstitielle et la glomérulonéphrite. Qui plus est, certains de ces traitements provoquent aussi une augmentation asymptomatique des taux de créatinine sérique en inhibant la sécrétion tubulaire active. Une femme de 79 ans était suivie pour une insuffisance rénale chronique de stade 4 A2 secondaire à un diabète de type 2 et à une hypertension de longue date. La patiente été diagnostiquée avec un carcinome mammaire invasif et a reçu du létrozole, un inhibiteur de l’aromatase. Un traitement au palbociclib, un inhibiteur sélectif de la kinase dépendante de la cycline, a été ajouté par la suite. Avant le début du traitement, le DFGe initial de la patiente avait fluctué de 25 à 28 mlmin1,73 m En absence de changements cliniques ou biochimiques suggérant une aggravation de la fonction rénale, la cystatine C sérique a été mesurée par dosage immunoturbidimétrique. Son taux (1,71 mgL) correspondait à un DFGe de 33 mlmin1,73 m Après sept mois, la mesure de la cystatine C sérique a été répétée pour évaluer une potentielle aggravation de la fonction rénale. Cette nouvelle mesure a révélé un DFGe de 35 mlmin1,73 m Ce rapport de cas et la revue de la littérature soulignent l’importance d’utiliser d’autres méthodes d’évaluation de la fonction rénale lorsque les patients suivent des traitements ciblés contre le cancer connus pour affecter la sécrétion tubulaire de créatinine, notamment les inhibiteurs de la kinase dépendante de la cycline (CDK46), les inhibiteurs de la polymérase poly-adénosine diphosphate ribose (PARP), les inhibiteurs de la tyrosine kinase (TK) et les inhibiteurs de la transition mésenchymateuse-épithéliale (TEM). L’utilisation de marqueurs du DFG autres que la créatinine, tels que la cystatine C et la scintigraphie rénale nucléaire, permettra une estimation plus précise de la fonction rénale dans le contexte approprié, évitant ainsi des tests diagnostiques invasifs et des ajustements inutiles des plans de traitement. On sait toutefois que certains traitements ciblés contre le cancer sont à l’origine de véritables lésions rénales. Par conséquent, les médecins doivent maintenir un haut degré de suspicion et envisager des examens invasifs etou l’arrêt ou la réduction des traitements lorsque d’autres mesures de la fonction rénale ne suggèrent pas une sous-estimation du DFG par la créatinine sérique.

Obesity and Type 2 Diabetes Mellitus Explained by the Free Energy Principle.

According to the free energy principle, all sentient beings strive to minimize surprise or, in other words, an information-theoretical quantity called variational free energy. Consequently, psychosocial stress can be redefined as a state of heightened expected free energy, that is, a state of expected surprise or uncertainty. Individuals experiencing stress primarily attempt to reduce uncertainty, or expected free energy, with the help of what is called an uncertainty resolution program (URP). The URP consists of three subroutines First, an arousal state is induced that increases cerebral information transmission and processing to reduce uncertainty as quickly as possible. Second, these additional computations cost the brain additional energy, which it demands from the body. Third, the program controls which stress reduction measures are learned for future use and which are not. We refer to an episode as good stress, when the URP has successfully reduced uncertainty. Failure of the URP to adequately reduce uncertainty results in either stress habituation or prolonged toxic stress. Stress habituation reduces uncertainty by flatteningbroadening individual goal beliefs so that outcomes previously considered as untenable become acceptable. Habituated individuals experience so-called tolerable stress. Referring to the Selfish Brain theory and the experimental evidence supporting it, we show that habituated people, who lack stress arousals and therefore have decreased average brain energy consumption, tend to develop an obese type 2 diabetes mellitus phenotype. People, for whom habituation is not the free-energy-optimal solution, do not reduce their uncertainty by changing their goal preferences, and are left with nothing but toxic stress. Toxic stress leads to recurrent or persistent arousal states and thus increased average brain energy consumption, which in turn promotes the development of a lean type 2 diabetes mellitus phenotype. In conclusion, we anchor the psychosomatic concept of stress in the information-theoretical concept of uncertainty as defined by the free energy principle. In addition, we detail the neurobiological mechanisms underlying uncertainty reduction and illustrate how uncertainty can lead to psychosomatic illness.

Perceptions of patients on factors affecting diabetes self-management among type 2 diabetes mellitus (T2DM) patients in Fiji A qualitative study.

Optimal glycemic control can be achieved when patients are adherent to self-management behaviours such as healthy diet, physical activity, monitoring of blood glucose, reducing the risk factors, ability to solve problems and healthy coping. In light of limited studies conducted, this study aimed to explore patients perceptions on factors affecting diabetes self-management among Type 2 Diabetes Mellitus (T2DM) patients of Labasa, Fiji. A qualitative study was employed to obtain data using semi-structured interviews conducted amongst T2DM patients attending clinics in 3 randomly selected health facilities in Labasa, Fiji from 15 Five themes emerged including awareness on diabetes, perceptions towards diabetes mellitus, social support and diabetes self-management, challenges in diabetes self-management, and cultural beliefs and practices. The findings of the study demonstrated lack of knowledge and attitude towards definition of diabetes and its complications. The self-management practices amongst patients were insufficient. There was poor financial support and lack of social support among patients. The results of this study highlighted various factors such as poor knowledge of diabetes and its complications, inadequate family support, financial burden and strong cultural beliefs and social norms affecting diabetes self-management. This study informs the need to identify the factors affecting diabetes self-management among T2DM patients.

Serum Untargeted Metabolomics Reveal Potential Biomarkers of Progression of Diabetic Retinopathy in Asians.

Diabetes Mellitus and Related Admission Factors Among Hospitalized Patients in King Abdul-Aziz University Hospital in Jeddah, Saudi Arabia.

Background Diabetes mellitus (DM) is a rapidly increasing serious health problem that affects the population all over the world. The increasing prevalence of DM in Saudi Arabia is reflected in our hospital admissions as well. This study aimed to assess the proportion of DM (including type 1 and type 2 diabetes) among hospitalized patients and the reasons for admissions to the medical unit at King Abdul-Aziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Methods We conducted a hospital record-based cross-sectional study at KAUH from January to April 2021. The study included all adult patients admitted to the internal medicine wards and isolation unit but excluded patients in the coronary care unit and those with gestational diabetes. We reviewed the medical records to collect demographic data, causes of admission, laboratory results, and outcomes. Results Among the hospitalized patients, 49.9% had DM. The most common associated risk factors and causes of admission among patients with DM were hypertension (HTN 73.2%) and dyslipidemia (43.1%). Other less common reasons for admission were heart failure (20.6%), coronavirus disease-2019 (COVID-19 17.8%), chronic kidney disease (CKD 14.5%), pneumonia (12.3%), and stroke (10%). Dyslipidemia, HTN, CKD, diabetic ketoacidosis, heart failure, and need for intensive care unit (ICU) admission were significantly higher in diabetic patients as compared to patients without diabetes. HTN, dyslipidemia, CKD, heart failure, stroke, acute abdomen, and malignancy were significantly higher in patients with type 2 diabetes. Among diabetic patients, those with non-Saudi nationality, low hemoglobin level, dyslipidemia, pneumonia, sepsis, and requiring ICU admission had a greater risk of death. Conclusions The high burden of DM on the secondary healthcare level in Saudi Arabia highlights the need for effective diabetes prevention and treatment strategies in primary care and hospital outpatient settings. Such measures would help reduce the hospitalization rate and ease the healthcare systems burden.

Boerhaave Syndrome An Unexpected Complication of Diabetic Ketoacidosis.

Boerhaave syndrome (BS) is a rare gastrointestinal condition related to esophageal rupture that carries a high mortality rate without prompt medical attention. BS is commonly associated with repeated episodes of severe retching, straining, or vomiting. Diabetic ketoacidosis (DKA), a serious acute complication of diabetes, is characterized in part by laboratory findings of profound hyperglycemia and ketoacidosis. Clinically, nausea and vomiting are seen commonly in DKA patients, which can often include repeated forceful retching, but rarely associated with esophageal rupture. In this article, we will describe a case of BS secondary to repeated episodes of emesis in the setting of DKA.

Inhibition of glucocorticoid synthesis alleviates cognitive impairment in high-fat diet-induced obese mice.

In addition to cardiovascular diseases, metabolic syndrome and type 2 diabetes mellitus, obesity is associated with cognitive deficits. In rodents, it has been shown that long-term high-fat diet (HFD) consumption leads to the alteration of hypothalamic-pituitary-adrenal (HPA) axis resulting in increased corticosterone release. However, mechanisms underpinning cognitive impairments induced by long-term HFD intake are unclear. Herein we evaluated the effects of systemic administration of glucocorticoid synthesis inhibitor metyrapone on cognitive performance assessed by novel object recognition test and plasma corticosterone levels evaluated by enzyme-linked immunosorbent assay in HFD-induced obese mice. We found that metyrapone treatment alleviated recognition memory impairments in HFD-induced obese mice. Furthermore, glucocorticoid synthesis inhibitor also lowered plasma corticosterone levels in HFD-induced obese mice. Our findings indicate that hyperactivation of HPA axis resulting in elevated circulating glucocorticoid levels leads to memory impairments in HFD-induced obese mice. We identify glucocorticoid system as a potential therapeutic target for treating cognitive deficits associated with obesity condition.

Culture-negative primary sternal osteomyelitis in a patient with uncontrolled type 2 diabetes mellitus.

Primary sternal osteomyelitis (PSO) is a rare condition defined as an infection of the sternal bone marrow with no contiguous source of infection. The overlap in symptoms of PSO with other cutaneous and malignant pathologies often leads to misdiagnosis and delay of appropriate care. In this case report, we outline the presentation of PSO in a 30 year-old male patient who was newly diagnosed with type 2 diabetes mellitus. The patient was successfully treated with antibiotic therapy alone, without need for surgical intervention. Interestingly, the patients workup returned with negative microbial cultures. To our knowledge, this patient represents the first reported case of a spontaneously presenting, culture-negative PSO.

Altered Tim-1 and IL-10 Expression in Regulatory B Cell Subsets in Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease with a complex aetiology. B cells play an important role in the pathogenesis of T1D. Regulatory B cells (Bregs) are a subset of B cells that produce and secrete the inhibitory factor interleukin-10 (IL-10), thereby exerting an anti-inflammatory effect. It was recently discovered that T-cell immunoglobulin mucin domain 1 (Tim-1) is essential for maintaining Bregs function related to immune tolerance. However, the detailed understanding of Tim-1 A total of 47 patients with T1D, 30 patients with type 2 diabetes (T2D) and 24 healthy controls were recruited in this study. Flow cytometry was used to measure the levels of different B cell subsets (including B cells, plasmablasts, and Bregs) in the peripheral blood. Radiobinding assays were performed to detect the antibody titres of T1D patients. In addition, the correlations between different B cell subsets and patient parameters were investigated. Compared with healthy controls, differences in frequency of Tim-1 Our study showed altered Tim-1 and IL-10 expression in regulatory B cell in T1D patients. Tim-1, as suggested by the present study, is associated with islet function and blood glucose levels. These findings indicate that Tim-1

Genome-scale metabolic modelling of the human gut microbiome reveals changes in the glyoxylate and dicarboxylate metabolism in metabolic disorders.

The human gut microbiome has been associated with metabolic disorders including obesity, type 2 diabetes, and atherosclerosis. Understanding the contribution of microbiome metabolic changes is important for elucidating the role of gut bacteria in regulating metabolism. We used available metagenomics data from these metabolic disorders, together with genome-scale metabolic modeling of key bacteria in the individual and community-level to investigate the mechanistic role of the gut microbiome in metabolic diseases. Modeling predicted increased levels of glutamate consumption along with the production of ammonia, arginine, and proline in gut bacteria common across the disorders. Abundance profiles and network-dependent analysis identified the enrichment of tartrate dehydrogenase in the disorders. Moreover, independent plasma metabolite levels showed associations between metabolites including proline and tyrosine and an increased tartrate metabolism in healthy obese individuals. We, therefore, propose that an increased tartrate metabolism could be a significant mediator of the microbiome metabolic changes in metabolic disorders.

The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus A Systematic Review and Meta-Analysis.

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder, some natural compounds are thought to be beneficial in improving the metabolic status of patients with T2DM. Curcumin is the main bioactive agent of turmeric, the impact of curcumin on T2DM is still controversial. This meta-analysis aimed to evaluate the effects of curcumin on lipids profile and glucose status in patients with T2DM. Randomized controlled trials (RCTs) examining the effects of curcumin on lipids profile and glycemic control of T2DM patients were searched in PubMed, Embase, Web of Science and Cochrane Library. Pooled estimates of weighted mean difference (WMD) were calculated between intervention and control groups using random-effects or fixed-effects model. Subgroup and sensitivity analyses were conducted to assess the effects. Nine eligible RCT with 604 subjects were included. The estimated pooled mean changes with curcumin were -18.97 mgdL (95% CI -36.47 to -1.47

StatPearls

Diabetes mellitus is a disease process that has been increasing globally and is estimated to affect more than 10% of adults in developed countries and 1 in 11 adults worldwide. Further estimations describe the total number of diabetes mellitus patients has quadrupled in the past 30 years. Diabetes mellitus is a chronic disease process that causes serious health consequences and increases the risk of developing health complications and comorbidities. Specifically, patients with diabetes are between two and four times more likely to develop a poor cardiovascular outcome than their non-diabetic counterparts. In a study analyzing over 57 articles related to cardiovascular and diabetes outcomes, encompassing over 4.5 million people in various studies, researchers have found that cardiovascular disease affects an estimated 32.2% of those diagnosed with type 2 diabetes mellitus (T2DM) and contributes to over 50% of all deaths. Throughout the years, research has suggested that in addition to having diabetes well under control, mitigating risk factors associated with diabetes mellitus may decrease the likelihood of cardiovascular disease and adverse events in patients with diabetes. However, there is no set algorithm to achieve this target, and a patient-centered approach, evaluating their specific risk factors, is warranted. Choice of medical therapy should be individualized to obtain the best possible outcome for each patient. Initial treatment rests on educating the patient about glycemic control and appropriate lifestyle changes such as tobacco cessation, increasing exercise, and reducing body weight. However, patients with established cardiovascular disease or those at high risk of this disease warrant special consideration to prevent poor outcomes. This activity describes the evaluation and management of cardiovascular risks in patients with type 2 diabetes mellitus and emphasizes the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (also known as GLP-1RAs, GLP-1 receptor agonists, incretin mimetics, or GLP-1 analogs) drugs in conjunction with insulin to mitigate this risk.

Diabetes (type 1 and type 2) in children and young people diagnosis and management

This guideline covers the diagnosis and management of type 1 and type 2 diabetes in children and young people aged under 18. The guideline recommends how to support children and young people and their families and carers to maintain tight control of blood glucose to reduce the long-term risks associated with diabetes. In Healthcare professionals, including those working in dental services. Commissioners and providers. Children and young people with type 1 or type 2 diabetes, and their families and carers.

Type 2 diabetes in adults management

This guideline covers care and management for adults (aged 18 and over) with type 2 diabetes. It focuses on patient education, dietary advice, managing cardiovascular risk, managing blood glucose levels, and identifying and managing long-term complications. In Healthcare professionals, including those working in dental services. Commissioners and providers. Adults with type 2 diabetes, and their families and carers.

Perceived value of self-monitoring blood glucose by primary care physicians and endocrinologists.

The value of self-monitoring blood glucose (SMBG) in patients with non-insulin-treated type 2 diabetes (NITT2DM) has been debated however, the practice remains common. Patient perception of SMBG has been documented in several qualitative studies. However, the literature is lacking on the perceived value of SMBG by providers. This study used a structured questionnaire to evaluate and compare the perceived value, recommended frequency, and utility of SMBG in patients with NITT2DM by primary care providers (PCPs) and endocrinologists. A total of 70 PCPs and 14 endocrinologists completed the questionnaire. The results suggest that PCPs and endocrinologists find the practice of SMBG valuable in NITT2DM and believe it promotes behavioral changes in their patients. However, endocrinologists tend to recommend more frequent SMBG and find SMBG values more useful in making medication decisions. Conversely, PCPs tend to find the hemoglobin A1c more valuable than SMBG in making medication adjustments.

Effectiveness and Safety of Ayurvedic Medicines in Type 2 Diabetes Mellitus Management A Systematic Review and Meta-Analysis.

Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness A systematic review and meta-analysis of randomized controlled trials.

Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). We searched PubMed, Cochrane Library, and grey literature from inception to 7 We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 ms. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 ms. SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Early Prediction of a Pre-Symptomatic Neurodegeneration Disorder by Measuring Macrophage Inhibitory Factor Level in Diabetic Patients.

The relationship between diabetes mellitus and neurodegenerative disorders has been of great interest. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine in which a variety of signaling cascades are activated through it. MIF has been involved in the pathogenesis of several diseases and can predict early pre-symptomatic stages of neurodegeneration in diabetic patients. To investigate whether serum MIF could predict brain neurodegeneration at the early pre-symptomatic stages in diabetic patients. We examined adults with type 2 diabetes mellitus and compared with normal control adults using a short form of the IQCODE and biochemical examination, including assessment of HA1C, fasting blood glucose, lipid profile, and MIF which was measured by ELISA technique. Correlations between parameters were studied. Computational PathLinker bioinformatic tool was used to search for potential pathway reconstructions for the insulinamyloid-βMIF signaling. We demonstrated that MIF level was increased in the serum at the early pre-symptomatic stages of neurodegenerative disorder in diabetic patients. In addition, network analysis demonstrates that insulin receptor substrate 1 can ameliorate amyloid-β protein precursor through COP9 signalosome complex subunit 5 that enhances MIF elevation. Diagnosis processes could not be used as routine examinations for still pre-symptomatic neurodegenerative disorders. This may be due to the time constraints and the heavy dependence on the physicians experience. Therefore, serum MIF level could predict brain neurodegeneration at the early pre-symptomatic stages in diabetic patients which may support its potential utility as a clinically useful biomarker.

Development and validation of a metabolite score for red meat intake an observational cohort study and randomized controlled dietary intervention.

Self-reported meat consumption is associated with disease risk but objective assessment of different dimensions of this heterogeneous dietary exposure in observational and interventional studies remains challenging. We aimed to derive and validate scores based on plasma metabolites for types of meat consumption. For the most predictive score, we aimed to test whether the included metabolites varied with change in meat consumption, and whether the score was associated with incidence of type 2 diabetes (T2D) and other noncommunicable diseases. We derived scores based on 781 plasma metabolites for red meat, processed meat, and poultry consumption assessed with 7-d food records among 11,432 participants in the EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort. The scores were then tested for internal validity in an independent subset (n 853) of the same cohort. In focused analysis on the red meat metabolite score, we examined whether the metabolites constituting the score were also associated with meat intake in a randomized crossover dietary intervention trial of meat (n 12, Lyon, France). In the EPIC-Norfolk study, we assessed the association of the red meat metabolite score with T2D incidence (n 1478) and other health endpoints. The best-performing score was for red meat, comprising 139 metabolites which accounted for 17% of the explained variance of red meat consumption in the validation set. In the intervention, 11 top-ranked metabolites in the red meat metabolite score increased significantly after red meat consumption. In the EPIC-Norfolk study, the red meat metabolite score was associated with T2D incidence (adjusted HR per SD 1.17 95% CI 1.10, 1.24). The red meat metabolite score derived and validated in this study contains metabolites directly derived from meat consumption and is associated with T2D risk. These findings suggest the potential for objective assessment of dietary components and their application for understanding diet-disease associations.The trial in Lyon, France, was registered at clinicaltrials.gov as NCT03354130.

Genetic trade-offs between complex diseases and longevity.

Longevity was influenced by many complex diseases and traits. However, the relationships between human longevity and genetic risks of complex diseases were not broadly studied. Here, we constructed polygenic risk scores (PRSs) for 225 complex diseasestraits and evaluated their relationships with human longevity in a cohort with 2178 centenarians and 2299 middle-aged individuals. Lower genetic risks of stroke and hypotension were observed in centenarians, while higher genetic risks of schizophrenia (SCZ) and type 2 diabetes (T2D) were detected in long-lived individuals. We further stratified PRSs into cell-type groups and significance-level groups. The results showed that the immune component of SCZ genetic risk was positively linked to longevity, and the renal component of T2D genetic risk was the most deleterious. Additionally, SNPs with very small p-values (p ≤ 1x10

Usefulness of fibrosis-4 (FIB-4) score and metabolic alterations in the prediction of SARS-CoV-2 severity.

Despite vaccination programs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a public health problem. Identifying key prognostic determinants of severity of the disease may help better focus health resources. The negative prognostic role for metabolic and hepatic alterations is established however, the interplay among different metabolic comorbidities and their interconnections with the liver have never been explored.The objective of this study is to evaluate the impact of liver alterations in addition to metabolic comorbidities as a predictor of SARS-CoV-2 severity. 382 SARS-CoV-2 patients were enrolled. Severe SARS-CoV-2 was diagnosed according to international consensus. Transaminases > 2 times the upper limit of normality (2ULN), hepatic steatosis (by ultrasound andor computed tomography in 133 patients), and FIB-4 defined liver alterations. All data were collected on admission. The results are severe SARS-CoV-2 infection in 156 (41%) patients (mean age 65 ± 17 60%males). Prevalence of obesity was 25% diabetes, 17% hypertension, 44% dyslipidaemia, 29% with 13% of the cohort with ≥ 3 metabolic alterations. Seventy patients (18%) had transaminases > 2ULN, 82 (62%) steatosis 199 (54%) had FIB-4 < 1.45 and 45 (12%) > 3.25. At multivariable analysis, ≥ 3 metabolic comorbidities (OR 4.1, CI 95% 1.8-9.1) and transaminases > 2ULN (OR 2.6, CI 95% 1.3-6.7) were independently associated with severe SARS-CoV-2. FIB-4 < 1.45 was a protective factor (OR 0.42, CI 95% 0.23-0.76). Hepatic steatosis had no impact on disease course. The presence of metabolic alterations is associated with severe SARS-CoV-2 infection, and the higher the number of coexisting comorbidities, the higher the risk of severe disease. Normal FIB-4 values are inversely associated with advanced SARS-CoV-2 regardless of metabolic comorbidities, speculating on use of these values to stratify the risk of severe infection.

A novel second-stage surgical strategy for severely obese patient with pancreatic neuroendocrine tumor a case report.

Severely obese patients can have other diseases requiring surgical treatment. In such patients, bariatric surgeries are considered a precursor to operations targeting the original disease for the purpose of reducing severe perioperative complications. Pancreatic ectopic fat deposition increases pancreas volume (PV) and thickness, which can worsen insulin resistance and islet β cell function. To address this problem, we present a novel two-stage surgical strategy performed on a severely obese patient with pancreatic neuroendocrine tumor (PNET) consisting of laparoscopic sleeve gastrectomy (LSG) as a metabolic surgery followed by laparoscopic spleen-preserving distal pancreatectomy (LSPDP). A 56-year-old man was referred to our hospital for further investigation of a pancreatic tumor. His initial body weight and body mass index (BMI) were 94.0 kg and 37.2 kgm We present a novel two-stage surgical strategy for a severely obese patient with PNET, consisting of LSG as a metabolic surgery for severe obesity, followed by LSPDP after confirmation of good weight loss and metabolic effects. LSG before pancreatectomy may have a potential to reduce pancreas thickness and recovery of islet β cell function in severely obese patients, thereby reducing the risk of clinically relevant POPF and post-pancreatectomy T2D onset.

Executive summary on the treatment of type 2 diabetes mellitus in elderly or frail individuals. 2022 update of the 2018 consensus document Treatment of type 2 diabetes mellitus in the elderly.

The population with type 2 DM (DM2) is highly heterogeneous, representing an important challenge for healthcare professionals. The therapeutic choice should be individualized, considering the functional status, frailty, the occurrence of comorbidities, and the preferences of patients and their caregivers. New evidence on the cardiovascular and renal protection of specific therapeutic groups and on the usefulness of new technologies for DM2 management, among other aspects, warrant an update of the consensus document on the DM2 in the elderly that was published in 2018.

The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes A secondary analysis of the D2d study.

Low blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes. 2423 participants were randomized to 4000 IUday of vitamin D Mean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (-0.45 %, 95%CI -0.75 to -0.15). In people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score. D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.

Inpatient Perioperative Euglycemic Diabetic Ketoacidosis Due to Sodium-Glucose Cotransporter-2 Inhibitors - Lessons From a Case Series and Strategies to Decrease Incidence.

To identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events. Electronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmolL, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA. A total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively. Euglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped.

Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors.

The organ protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors may be beneficial against infectious complications. This real-world study aims to compare the risk of pneumonia and sepsis between SGLT2 inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes. Using a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System CDARS), we included patients initiated on SGLT2 inhibitors or DPP-4 inhibitors between January 01, 2015 and December 31, 2019 through 12 propensity score matching. The primary outcomes were incident events of pneumonia, sepsis and the related mortality. Cox proportional hazards analysis was used to compare the risk of incident pneumonia and sepsis for SGLT2 inhibitors versus DPP-4 inhibitors. After propensity score matching, 10,706 new users of SGLT2 inhibitors and 18,281 new users of DPP-4 inhibitors were included. The mean age of all eligible subjects were 60 years (SD 11.07) and 61.1% were male. There were 309 pneumonia events incidence rate per 1000 person-years (IR) 11.38 among SGLT2 inhibitors users and 961 events (IR 20.45) among DPP-4 inhibitors users, with lower risk of pneumonia among SGLT2 inhibitors users (adjusted HR 0.63 95%CI 0.55-0.72, p<0.001). Similarly, SGLT2 inhibitors users had lower incidence of sepsis 164 (IR6.00) vs. 610 (IR12.88) events as well as associated risk of incident sepsis (HR 0.52 95% CI 0.44-0.62, p<0.001), compared to DPP-4 inhibitors users. Outcome analyses showed that SGLT2 inhibitors were associated with lower risk of pneumonia-related death (HR 0.41 95%CI 0.29-0.58, p<0.001), sepsis-related death (HR 0.39 95%CI 0.18-0.84, p<0.05), and infection-related death (HR 0.43 95%CI 0.32-0.57, p<0.001), compared to DPP-4 inhibitors users. Results were consistent when stratified by age, sex, pre-existing cardiovascular disease, and type of SGLT2 inhibitors. We provide real-world evidence that irrespective of age, sex, prior-existing cardiovascular disease, or type of SGLT2 inhibitors used, patients with type 2 diabetes initiated on SGLT2 inhibitors have lower incidence of pneumonia and sepsis as well as mortality risk associated with pneumonia, sepsis, and infectious diseases, compared with those initiated on DPP-4 inhibitors.

Crosstalk between incretin hormones, Th17 and Treg cells in inflammatory diseases.

Intestinal epithelial cells constantly crosstalk with the gut microbiota and immune cells of the gut lamina propria. Enteroendocrine cells, secrete hormones, such as incretin hormones, which participate in host physiological events, such as stimulating insulin secretion, satiety, and glucose homeostasis. Interestingly, evidence suggests that the incretin pathway may influence immune cell activation. Consequently, drugs targeting the incretin hormone signaling pathway may ameliorate inflammatory diseases such as inflammatory bowel diseases, cancer, and autoimmune diseases. In this review, we discuss how these hormones may modulate two subsets of CD4 T cells, the regulatory T cells (Treg)Th17 axis important for gut homeostasis thus, preventing the development and progression of inflammatory diseases. We also summarize the main experimental and clinical findings using drugs targeting the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1) signaling pathways and their great impact on conditions in which the TregTh17 axis is disturbed such as inflammatory diseases and cancer. Understanding the role of incretin stimulation in immune cell activation and function, might contribute to new therapeutic designs for the treatment of inflammatory diseases, autoimmunity, and tumors.

Cognitive Behavioral Therapy for self-care behaviors with type 2 diabetes mellitus patients A systematic review.

Self-care behavior is associated with the risk of microvascular and macrovascular complications. Self-care behaviors can be improved through positive thinking, attitude, and knowledge. Cognitive behavioral therapy (CBT) can be one of the interventions for improving self-care behaviors. However, the ideal model and duration of the intervention and an effective assessment instrument to measure the improvement in self-care behaviors remain unidentified. Therefore, this review aimed to assess the effectiveness of CBT, including its models, duration, and instruments, in improving self-care behaviors in patients with type 2 diabetes mellitus (T2DM). The Scopus, Cochrane Library, PubMed, EBSCO Host, Directory of Open Access Journals, GARUDA, Taylor Francis, and Gray Literature databases were systematically searched to identify studies that were in English and published in 2011-2021. The quality of the identified articles was assessed using The Critical Appraisal Skill Programme. We found 368 patients in seven randomized controlled trials. CBT was significantly effective in improving overall self-care behavior, including blood glucose monitoring, physical activity, and medication compliance. Individual and group CBT interventions applied face-to-face, via telephone, and via internet show an increase in self-care behavior in patients with T2DM. The duration of treatment had a significant effect at 3 months to 1 year with 12-21 sessions. CBT is performed by a CBT licensed nurse or psychiatrist, nutritionist, CBT psychologist with experience in diabetes care, doctors, research students.

The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion.

SYT11 and SYT13, two calcium-insensitive synaptotagmins, are downregulated in islets from type 2 diabetic donors, but their function in insulin secretion is unknown. To address this, we investigated the physiological role of these two synaptotagmins in insulin-secreting cells. Correlations between gene expression levels were performed using previously described RNA-seq data on islets from 188 human donors. SiRNA knockdown was performed in EndoC-βH1 and INS-1 83213 cells. Insulin secretion was measured with ELISA. Patch-clamp was used for single-cell electrophysiology. Confocal microscopy was used to determine intracellular localization. Human islet expression of the transcription factor PDX1 was positively correlated with SYT11 (p 2.4e SYT11 and SYT13 have similar localization and transcriptional regulation, but they regulate insulin secretion differentially. While downregulation of SYT11 might be a compensatory mechanism in type-2 diabetes, downregulation of SYT13 reduces the insulin secretory response and overrules the compensatory regulation of SYT11 in a way that could aggravate the disease.

Quality of chronic care for patients with type 2 diabetes in practices with and without a Clinical Specialized Medical Assistant (CSMA) - a cross-sectional study from Switzerland.

Due to Switzerlands shortage of general practitioners (GPs), task shifting through interprofessional collaboration is needed to relieve GPs workload and allow the continued provision of quality care. The profession of specialized medical assistant (SMA) was created in Switzerland several years ago to provide a career advancement opportunity for medical practice assistants (MPAs) and intended to counteract the increasing scarcity of resources in primary care. Clinical specialized medical assistants (CSMAs) are trained to care for a set of chronic conditions, such as diabetes. We aimed to compare the quality of care for patients with type 2 diabetes in practices with and without CSMAs. Further, we aimed to investigate whether evidence exists that CSMA care models may allow for task shifting and the provision of interprofessional care while maintaining a high quality of care and to assess patient experiences with diabetes care in both care models. The present study was a paper-based cross-sectional survey of patient data. A total of 171 patients with type 2 diabetes who had been under the care of either a GP with CSMA (91 patients) or a GP without CSMA (80 patients) for at least one year were consecutively recruited for the study. Data were collected from mid-September 2020 to mid-June 2021. For the statistical analyses, we used descriptive statistics and t-tests. Patients from both practice types were comparable in age, gender and diabetes-relevant factors such as Body Mass Index, smoking status and blood pressure. Overall, patients in both models received a high quality of care (Diabetes Treatment Satisfaction Questionnaire, DTSQ >3236 points, SGED >75 points) and a low treatment burden (Treatment Burden Questionnaire, TBQ <20150 points). When comparing patients DTSQ, SGED and TBQ in both groups, we found no significant differences in diabetes-specific satisfaction (32.1 SD 3.6 vs. 32.4 SD 3.8, p 0.7), SGED score (80.2 SD 8.5 vs. 75.9 SD 4.8, p 0.18) or treatment burden (19.2 SD 15.6 vs. 18.8 SD 21.4, p 0.89). Our comparison of patient-reported outcomes and SGED criteria of patients with type 2 diabetes in practices with and without CSMAs showed an equally high quality of care and a low treatment burden. More research is needed on the long-term effects and benefits of the care provided by CSMAs and which other tasks could be shifted to CSMAs to reduce the burden on GPs in the future. At the same time, an increasing number of patients with type 2 diabetes will require high-quality primary care.

Part Three A Brief Primer of Non-Insulin Treatments for Type 2 Diabetes Mellitus in Older People.

Diabetes is a heterogeneous condition that manifests differently in each patient. Fortunately, there are multiple different medication classes that can be used to help patients achieve their treatment goals. Diabetes is highly prevalent in older people, including patients who have been living with the condition for many years and those who are newly diagnosed. It is essential for senior care pharmacists to evaluate patient-specific goals, compelling indications, and risks and benefits of treatment. When evaluating therapy appropriateness, pharmacists must take into consideration the impact of medication therapy beyond glucose-lowering effects, including the overall impact on cardiovascular, renal, heart failure, and weight-related outcomes.

Independent Predictors of Discontinuation of Diabetic Medication after Sleeve Gastrectomy and Gastric Bypass.

Both gastric bypass and sleeve gastrectomy can induce diabetes remission. However, deciding which procedure to perform is challenging, because remission rates and morbidity can vary, depending on patient factors as well as disease severity. Using a statewide bariatric-specific data registry, we evaluated all patients undergoing sleeve gastrectomy and gastric bypass between 2006 and 2019 who reported taking either oral diabetic medication alone or who were on insulin before surgery and who also had 1-year follow-up (n11,664). Multivariate regression was used to identify independent predictors for discontinuation of oral diabetic medication or insulin, respectively, and risk-adjusted complication rates were compared between procedure types among each group. At 1-year after surgery, 85.7% of patients reported discontinuation of oral diabetic medication and 66.6% reported discontinuation of insulin. Gastric bypass was an independent predictor for insulin discontinuation (odds ratio 1.17 CI 1.01 to 1.35 p 0.0329) however, procedure type was not associated with discontinuation of oral medication alone. Risk-adjusted complication rates were significantly higher after gastric bypass than after sleeve gastrectomy, regardless of whether the patient was taking oral diabetic medications alone or was on insulin (11.2% vs 4.8%, p < 0.0001 and 12.0% vs 7.4%, p < 0.0001, respectively). Patients requiring insulin experience higher rates of insulin discontinuation after gastric bypass, but also have significantly higher complication rates when compared to sleeve gastrectomy. However, if patients are on oral diabetic medication alone, rates of medication discontinuation at 1 year are greater than 85% and procedure type is not predictive. Disease severity is an important factor when deciding on the optimal procedure for diabetes.

Household food insecurity is associated with diabetic ketoacidosis but not severe hypoglycemia or glycemic control in youth and young adults with youth-onset type 2 diabetes.

To examine the association between household food insecurity (HFI), glycemic control, severe hypoglycemia and diabetic ketoacidosis (DKA) among youth and young adults (YYA) with youth-onset type 2 diabetes. This cross-sectional study included 395 YYA with type 2 diabetes from the SEARCH for Diabetes in Youth Study (2015-2019). HFI was reported by young adult participants or parents of minor participants via the US Household Food Security Survey Module. Glycemic control was assessed by HbA Approximately 31% reported HFI in the past 12 months. Mean HbA HFI was associated with markedly increased odds of DKA but not with glycemic control or severe hypoglycemia. Future research among YYA with type 2 diabetes should evaluate longitudinally whether alleviating HFI reduces DKA.

Initiating or Switching to Insulin DegludecInsulin Aspart in Adults with Type 2 Diabetes A Real-World, Prospective, Non-interventional Study Across Six Countries.

Insulin degludecinsulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (a basal insulin) and insulin aspart (a prandial insulin). The aim of this study was to investigate clinical outcomes in people with type 2 diabetes (T2D) after initiating IDegAsp treatment in a real-world setting. This 26-week, open-label, non-interventional study was conducted in Australia, India, Malaysia, Philippines, Saudi Arabia, and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp from antidiabetic treatments (including oral antidiabetic drugs, basal insulin, basal-bolus insulin, premix insulin, and glucagon-like peptide 1 receptor agonist) per local clinical practice. Compared with baseline, there was significant improvement in HbA1c at end of study (EOS, first visit within weeks 26-36 estimated change - 1.4% 95% CI - 1.51 - 1.29 P < 0.0001 primary outcome). From baseline to EOS, there were significant reductions in fasting plasma glucose (- 2.7 mmolL 95% CI - 2.98 - 2.46 P < 0.0001), body weight (- 1.0 kg 95% CI - 1.51 - 0.52 P < 0.0001), and basal insulin dose in insulin-experienced participants (- 2.3 units 95% CI - 3.51 - 1.01 P < 0.001). The incidence rates of non-severe (overall and nocturnal) and severe hypoglycaemia decreased significantly (P < 0.001) between the period before baseline and before EOS. In adults with T2D, initiating or switching to IDegAsp from previous antidiabetic treatment was associated with improved glycaemic control, lower basal insulin dose (in insulin-experienced participants), and lower rates of hypoglycaemia. Clinical trial registration NCT04042441.

Perioperative management of diabetes in patients undergoing bariatric and metabolic surgery a narrative review and the Cleveland Clinic practical recommendations.

Bariatric and metabolic surgery is an effective treatment for patients with severe obesity and obesity-related diseases. In patients with type 2 diabetes, it provides marked improvement in glycemic control and even remission of diabetes. In patients with type 1 diabetes, bariatric surgery may offer improvement in insulin sensitivity and other cardiometabolic risk factors, as well as amelioration of the mechanical complications of obesity. Because of these positive outcomes, there are increasing numbers of patients with diabetes who undergo bariatric surgical procedures each year. Prior to surgery, efforts should be made to optimize glycemic control. However, there is no need to delay or withhold bariatric surgery until a specific glycosylated hemoglobin target is reached. Instead, treatment should focus on avoidance of early postoperative hyperglycemia. In general, oral glucose-lowering medications and noninsulin injectables are not favored to control hyperglycemia in the inpatient setting. Hyperglycemia in the hospital is managed with insulin, aiming for perioperative blood glucose concentrations between 80 and 180 mgdL. Following surgery, substantial changes of the antidiabetic medication regimens are common. Patients should have a clear understanding of the modifications made to their treatment and should be followed closely thereafter. In this review article, we describe practical recommendations for the perioperative management of diabetes in patients with type 2 or type 1 diabetes undergoing bariatric surgery. Specific recommendations are delineated based on the different treatments that are currently available for glycemic control, including oral glucose-lowering medications, noninsulin injectables, and a variety of insulin regimens.

Randomized Comparison of Initiating the Fixed-Ratio Combination of iGlarLixi or Biosimilar Insulin Glargine Together With Gliclazide in Participants of South Asian Origin With Type 2 Diabetes VARIATION 2 SA Trial.

The objective of this study was to compare initiation of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) vs insulin glargine U100 (iGlar) along with gliclazide, exclusively in people of South Asian origin with type 2 diabetes (T2D). The Variability of glucose Assessed in a Randomized trial comparing the Initiation of A Treatment approach with biosimilar basal Insulin analog Or a titratable iGlarLixi combinatioN in type 2 diabetes among South Asian participants (VARIATION 2 SA) trial (ClinicalTrials.gov identifier NCT03819790) randomized insulin-naïve adults with T2D having glycated hemoglobin (A1C) 7.1% to 11% to initiate either iGlarLixi or iGlar gliclazide. Insulin doses were titrated similarly to a prebreakfast glucose target of 4.0 to 5.5 mmolL. Average time in range (TIR) on a masked continuous glucose monitor (CGM), A1C, fasting plasma glucose (FPG) and weight were assessed at the end of the 12-week treatment period. Mean baseline characteristics for the 104 randomized participants were similar between treatment groups, including the following age, 59±11 years diabetes duration, 13.7±7.3 years and A1C, 8.5%±1.2%. Coprimary outcomes of average TIRs within 24- and 12-h (6 am to 6 pm) periods at the end of trial were 70.5%±16.8% and 72.9%±17.6% for iGlarLixi, whereas these TIRs were 65.6%±21.6% and 67.3%±20.7% for the iGlar gliclazide regimen, respectively, with no significant differences between groups (p0.35 for 24-h TIR and p0.14 for 12-h TIR). No significant difference in secondary outcomes was observed between treatment groups. Self-reported hypoglycemic events throughout the trial period and CGM-reported hypoglycemia (<4 and <3 mmolL) were similar between randomized treatments. Initiation of iGlarLixi resulted in similar TIR, A1C, FPG, weight and hypoglycemia compared with the more affordable option of starting iGlar gliclazide in adults of South Asian origin with T2D.

Association of D-dimer with long-term prognosis in type 2 diabetes mellitus patients with acute coronary syndrome.

Type 2 diabetes mellitus (DM) accounts for more and more individuals worldwide. D-dimer has been demonstrated to be associated with cardiovascular diseases. The aim is to study the potential impact of D-dimer on the long-term prognosis of acute coronary syndrome (ACS) in the special population with type 2 DM. A total of 2265 consecutive patients with DM and ACS were eligible in the study. Patients were divided into four groups according to quartiles of D-dimer concentration. Univariate and multivariate Cox regression analysis were conducted to explore the prognostic value of D-dimer for future outcomes. Patients with higher level of D-dimer presented with higher percentage of major adverse cardiovascular events (MACEs) (23.7%), all-cause death (18.3%) and cardiovascular (CV) death (9.4%) in Quartile 4. In multivariate Cox regression analysis, D-dimer was demonstrated to be independently associated with MACEs, all-cause death and CV death. The prognostic value of D-dimer is still significant in subgroups of HbA1C <7% and ≥7%. In Kaplan-Meier analysis, higher D-dimer showed poorer prognosis in MACEs, all-cause death and CV death (all log rank p < 0.001). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis is 0.609 for MACEs, 0.708 for all-cause death, 0.747 for CV death (p < 0.001). The present study demonstrated the independent predictive value of D-dimer for outcomes in DM patients with ACS. In addition, for the first time, we explored the prognostic value in different glucose control status.

Cardiovascular events after a dramatic reduction of HbA1c in hospitalized subjects with type 2 diabetes and high long-term glucose exposure.

In long-lasting diabetes, a dramatic reduction of HbA1c can precede adverse events such as worsening retinopathies or painful neuropathies. We have now analyzed its possible link with later cardiovascular events in subjects with type 2 diabetes, according to their long-term glucose exposure evaluated by skin autofluorescence (SAF) measured with an AGE-READER (Diagnoptics, Groningen, The Netherland). We studied retrospectively a cohort of patients hospitalized for uncontrolled andor complicated type 2 diabetes from 2009 to 2017. A previous dramatic reduction of HbA1c was defined by more than -1.5 %4 months, and later cardiovascular events as myocardial infarction, stroke, revascularization procedures, and cardiovascular-related death. Survival analyses were performed before and after categorizing the subjects for their SAF. The 386 subjects were 57.5 % men, 62 ± 9 years old, with a 14 ± 9 years duration of diabetes, most were treated by insulin (63.7 %). The dramatic HbA1c reducers (-3.0 ± 1.5 %) represented 16.5 % of the population. During the 51 months (IQR 30-71) of follow-up, 53 cardiovascular events occurred and were related to the SAF (2.70 ± 0.64 AUs). Linkage was established between the SAF, the reduction of HbA1c and the cardiovascular events (p 0.017). With a SAF higher than the median (2.65 AUs), the dramatic reduction of HbA1c was related to later cardiovascular events (HR 3.84, 95%CI 1.68-8.76). A dramatic decline of HbA1c leads to a higher risk of cardiovascular events in hospitalized subjects with type 2 diabetes and a high long-term glucose exposure.

An Evaluation of Alternative Technology-Supported Counseling Approaches to Promote Multiple Lifestyle Behavior Changes in Patients With Type 2 Diabetes and Chronic Kidney Disease.

Although technology-supported interventions are effective for reducing chronic disease risk, little is known about the relative and combined efficacy of mobile health strategies aimed at multiple lifestyle factors. The purpose of this clinical trial is to evaluate the efficacy of technology-supported behavioral intervention strategies for managing multiple lifestyle-related health outcomes in overweight adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). Using a 2 × 2 factorial design, adults with excess body weight (body mass index ≥27 kgm Of 256 randomized participants, 186 (73%) completed 6-month assessments. Compared to the ADVICE group, mHealth interventions did not result in significant changes in weight loss, or urinary sodium and phosphorus excretion. In aggregate analyses, groups receiving mobile self-monitoring had greater weight loss at 3 months (P .02), but between 3 and 6 months, weight losses plateaued, and by 6 months, the differences were no longer statistically significant. When engaging patients with T2D and CKD in multiple behavior changes, self-monitoring diet and physical activity demonstrated significantly larger short-term weight losses. Theory-based behavioral counseling alone was no better than baseline advice and demonstrated no interaction effect with self-monitoring.

Polyol pathway and redox balance in diabetes.

Diabetes is a major public health disease that is globally approaching epidemic proportions. One of the major causes of type 2 diabetes is either a defect in insulin secretion or insulin action which is usually caused by a combination of genetic and environmental factors. Not only these factors but others such as deregulation of various pathways, and oxidative stress are also known to trigger the redox imbalance in diabetics. Increasing evidences suggest that there are tight interactions between the development of diabetes and redox imbalance. An alternate pathway of glucose metabolism, the polyol pathway, becomes active in patients with diabetes that disturbs the balance between NADH and NAD . The occurrence of such redox imbalance supports other pathways that lead to oxidative damage to DNA, lipids, and proteins and consequently to oxidative stress which further ascend diabetes and its complications. However, the precise mechanism through which oxidative stress regulates diabetes progression remains to be elucidated. The understanding of how antioxidants and oxidants are controlled and impact the generation of oxidative stress and progression of diabetes is essential. The main focus of this review is to provide an overview of redox imbalance caused by oxidative stress through the polyol pathway. Understanding the pathological role of oxidative stress in diabetes will help to design potential therapeutic strategies against diabetes.

Role of olmesartan in ameliorating diabetic nephropathy in rats by targeting the AGEPKC, TLR4P38-MAPK and SIRT-1 autophagic signaling pathways.

Diabetic nephropathy (DN) is one of the most serious consequences of diabetes and the most common reason for end-stage renal disease. The current study was set out to investigate the ability of olmesartan medoxomil (OM) to treat DN by evaluating the reno-protective effects of this drug on fatfructosestreptozotocin (FFrSTZ)-induced diabetic rat model. This model was induced by feeding rats high FFr diet for 7 weeks followed by injection of a single sub-diabetogenic dose of STZ (35mgkg i.p). The FFrSTZ-induced diabetic rats were orally treated with either OM (10 mgkg) or pioglitazone (10 mgkg) as a standard drug daily for four consecutive weeks. FFrSTZ-induced diabetic rats propagated inflammatory, oxidative, and fibrotic events. OM was able to oppose the injurious effects of diabetes it significantly reduced the elevated levels of advanced glycated end products (AGEs) and downregulated PKC gene expression, therefore, indicating its antioxidant capacity evidenced by mitigation in GSH, MDA renal content. Moreover, OM impaired the inflammatory cascade by suppressing the elevated level of renal TLR4 as well as diminished the inflammatory profibrotic cytokine TGF-β1. Additionally, OM was able to turn off the MAPK cascade mediated by an upsurge in renal angiotensin 1-7 content and decrease the level of renal tubular injury marker, KIM-1. Furthermore, OM enhanced the autophagic activity pathway by upregulating of gene expression of SIRT-1. The histopathological examination confirmed these results. Finally, OM protected against type 2 diabetes-related nephropathy complications by altering inflammatory pathways, oxidative, fibrotic, and autophagic processes triggered by renal glucose overload. This study shows that OM has a reno-protective effect against DN in rats by inhibiting the AGEPKC, TLR4P38-MAPK, and SIRT-1 autophagic signaling pathways.

Furostanol saponins from Asparagus racemosus as potential hypoglycemic agents.

Bioactivity guided phytochemical investigation led to isolation of six undescribed furostanol saponins, furoasparoside A-F along with five known compounds, gallic acid, methyl gallate, quercetin-3-O-β-glucopyranoside, liquiritigenin 4

Simiao Wan modulates the gut microbiota and bile acid metabolism during improving type 2 diabetes mellitus in mice.

Gut microbiota coupled with their metabolites (bile acids, BAs) get involved in diabetic pathogenesis. Simiao Wan is a famous traditional Chinese formula consisting on Phellodendron chinense C.K.Schneid. (Rutaceae), Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae) and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Poaceae), and used to treat gouty arthritis and hyperuricemia for thousands of years. However, the mechanisms underlying its beneficial efficacy on diabetes still needs to be explored. Our study was performed to reveal the effects of the 75% ethanol extraction of Simiao Wan (SMW) on diabetes, gut microbiota and bile acids (BAs) in diabetic mice. The effects of SMW on diabetes were evaluated in mice treated by high-fat diet (HFD)streptozotocin (STZ). The 16S rDNA sequencing and BAs metabolomics were performed to assess the changes of BAs profiles and gut microbiota induced by SMW. Western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of SMW. SMW significantly improved insulin resistance and hepatic lipid accumulation in HFDSTZ mice. It remarkably enriched in the bacteria Allobaculum, Clostridium, Akkermansia, Lactobacilus and Bilophila whereas decreased Coprococcus and Halomonas in diabetic mice. Furthermore, the profiles of BAs were also modulated by SMW, indicated by the reduction of conjugated BAs and 12α-OHnon-12α-OH BAs ratio in liver as well as the increase of primary BAs in feces. SMW also activated farnesoid X receptor and inhibited sterol regulatory element-binding protein-1 expression, contributing to its beneficial actions on lipid accumulation in liver. Our results showed that SMW exerted its beneficial effects on insulin resistance and hepatic lipid accumulation indirectly through regulating profiles of gut microbe and BAs.

Liraglutide Plus Dapagliflozin for High Uric Acid and Microalbuminuria in Diabetes Mellitus Complicated With Metabolic Syndrome.

Diabetes mellitus (DM) represents an emerging epidemic, poses serious threats to human health, and can seriously compromise patients quality of life (QoL). Currently, no cure exists for DM. Some studies have found that both liraglutide and dapagliflozin have great therapeutic potential in preventing and treating DM and its complications. The study aimed to examine the impact of liraglutide plus dapagliflozin on high uric acid (UA) and microalbuminuria (MAU) in patients with diabetes mellitus (DM) complicated with metabolic syndrome (MS). The research team designed a randomized controlled trial. The study took place at the Second Affiliated Hospital of Nanjing Medical University in Nanjing, Jiangsu, China. Participants were 125 patients with DM complicated with MS who were treated in the outpatient clinic of the endocrinology department at the hospital between January 1, 2020 and December 31, 2021, with 68 in the intervention group and 57 in the control group. The intervention and control groups both received 0.6 mg of liraglutide. The intervention group also received 5 mg of dapagliflozin once a day. The dosages were increased at one week after baseline based on the participants condition. Therapeutic effects, glycolipid metabolism, inflammation, uric acid (UA), microalbuminuria (MAU), cardiac function, and quality of life (QoL) were compared between the two groups. Postintervention, the clinical efficacy was significantly higher in the intervention group than in the control group. The intervention group had significantly lower glycolipid metabolism and inflammatory-factor levels than the control group UA and MAU had declined in both groups but were significantly lower in the intervention group. The left ventricular ejection fraction (LVEF) increased and the left ventricular end diastolic diameter (LVEDd) decreased in both groups, but the intervention group had significantly greater changes as compared with those in the control group. The intervention group was also superior to the control group in patients QoL. Liraglutide plus dapagliflozin has highly therapeutic effect for patients with DM complicated with MS and can effectively reduce UA and MAU levels. The current research team will launch a more comprehensive analysis as soon as possible to obtain the most accurate results.

Synchronous Health Care Delivery for the Optimization of Cardiovascular and Renal Care in Patients with Type 2 Diabetes.

The current care model of type 2 diabetes (T2D) and its complications appears to be asynchronous with patient care divided by specialty. This model is associated with low use of guideline-directed medical therapies. The use of integrated care models has been well described in the management of patients with T2D this usually includes an endocrinologist coupled with a nutritionist and nurse. However, physician-based care models are largely asynchronous, whereby the patient requires multiple different siloed specialties to manage their health care. To date, there has been limited exploration of synchronous care delivery, i.e., whereby multi-comorbid patients with T2D are seen simultaneously by health care providers from endocrinology, cardiology, and nephrology to optimize use of guideline-directed medical therapies (GDMT). Given the rising complexity of patients with T2D, further research is needed on the role of synchronous health care delivery in optimizing the use of GDMT and improving patient outcomes.

Machine learning algorithm to evaluate risk factors of diabetic foot ulcers and its severity.

Early identification of the risk factors associated with development of diabetic foot ulcer (DFU) can be facilitated using machine learning techniques. The aim of this study is to find out the association of various clinical and biochemical risk factors with DFU and develop a prediction model using different machine learning algorithms. Eighty each of type 2 diabetes mellitus (T2DM) with DFU and (T2DM) without DFU were enrolled for this observational study. Clinical and laboratory data were analysed using different machine learning algorithms Support vector machines (SVM-Poly K), Naive Bayes (NB), K-nearest neighbour (KNN), random forest (RF) and three ensemble learners Stacking C, Bagging and AdaBoost for constructing prediction models for discriminating between the two groups (stage I classification) and ulcer type classification (stage II classification). Ensemble learning performed better than individual classifiers in terms of various performance evaluation metrics. New risk factors like ApoA1 and IL-10 for development of DFU in diabetes mellitus were identified. IL-10 along with uric acid could discriminate the grades of ulcers according to its severity. Decision fusion strategy using Stacking C algorithm resulted in enhanced prediction accuracy for both the stages of classification which can be used as a complementary method for computational screening for DFU and its subtypes. Current methodology for T2DM with DFUT2DM without DFU and ulcer type classification.

Increased levels of insulin-degrading enzyme in patients with type 2 diabetes mellitus.

Decreasing levels of serum insulin-degrading enzyme (IDE) have been associated with an increased risk for Alzheimer´s disease (AD) in patients with type 2 diabetes mellitus (T2DM). Research on serum IDE levels in patients with T2DM is sparse and the aim of this study was to explore serum levels of IDE in patients with T2DM. Blood serum samples were obtained from a biobank. Samples from subjects with T2DM and without metabolic disease were divided into subgroups lifestyle treatment (n 10), oral antidiabetic treatment (n 17), insulin treatment (n 20) and metabolically healthy controls (n 18). Serum levels of IDE were analysed using specific ELISA assays. Serum levels of IDE were elevated in subjects with T2DM compared to metabolically healthy individuals (p 0.033). No significant differences were detected between treatment subgroups. The present study indicates that patients with T2DM have increased serum IDE levels, compared to metabolically healthy individuals. However, for IDE to be clinically useful as a biomarker, its full function and possible use needs to be further elucidated in larger studies showing reproducible outcomes.

A Narrative Review of Diabetic Kidney Disease Previous and Current Evidence-Based Therapeutic Approaches.

Diabetic kidney disease (DKD) is one of the most important diabetic complications. DKD is also the most common cause of chronic kidney disease (CKD) and end-stage renal disease. This review focused on potential therapeutic drugs for which there is established evidence of treatment for DKD. The earliest evidence for DKD treatment was established with renin-angiotensin system (RAS) inhibitors however, their efficacy was partial. Recently, the sodium-glucose co-transporter 2 (SGLT2) inhibitors, including empagliflozin (EMPA-REG Outcome), canagliflozin (CREDENCE trial), and dapagliflozin (DAPA-CKD), demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. Additionally, incretin-based therapeutic agents, such as glucagon-like peptide 1, liraglutide (LEADER), and dipeptidyl peptidase 4 inhibitors, linagliptin (CARMERINA) have elicited vasotropic actions, suggesting a potential for reducing the risk of DKD. Until recently, mineralocorticoid receptor antagonists (MRAs) have not been suitable for DKD treatment because of their adverse effect of hyperkalemia. In contrast, finerenone, a non-steroidal MRA, significantly reduced renal composite endpoint without severe hyperkalemia that would force its discontinuation (FIDELIO-DKD). Thus, the mainstay treatments of DKD are RAS inhibitors, SGLT2 inhibitors, incretin-based therapeutic agents, and non-steroidal MRA, or in other words, the DKD fantastic four.

Predictive factors in treatment response of malignant external otitis.

To evaluate the prevalence and impact of various predictive factors including diabetes control in malignant external otitis (MEO) treatment response. In a cross-sectional study on MEO patients, we defined treatment response with three indices ESR level decrease, hospitalization period, and systemic antifungal drug usage. The impact of diabetes control and other predictive factors on these indices have been evaluated. Overall, 164 patients with a mean age of 67.8 ± 9.7 years were included. Cranial nerve involvement was present in 56 patients. Nine patients had immunodeficiency. 19.5% of cases had leukocytosis. Diabetes mellitus was present in 156 patients, suffering for an average of 13.9 ± 8.6 years. The overall mean hemoglobin A1C (HbA1c) level was 8.3% (4.4-12.8%), and the mean fasting blood sugar was 146.4 mgdl (63-292 mgdl). 29.3% of patients had good diabetes control before admission (HbA1c < 7%), 54.9% had poor control (7% < HbA1c < 10%) and 15.9% had very poor glycemic control (HbA1c > 10%). The predictive role for the following factors were not statistically significant age, gender, comorbidities, diabetes, diabetes management method used before and during hospitalization, diabetes duration, leukocytosis, immunodeficiency, fasting blood sugar level, HbA1c level, glycemic control index, and insulin amount. However, CRP level with a mean value of 34.3 mgL showed a significant correlation with ESR decrease, hospitalization period, and antifungal drug usage. CRP level could be used as a predictor for the hospitalization period, the need for systemic antifungal and ESR level decrease. It would be helpful to check the CRP level at the time of diagnosis to predict the hospitalization period and the necessity of systemic antifungal management to adjust the treatment strategy.

Progressive stages of dysmetabolism are associated with impaired biological features of human cardiac stromal cells mediated by the oxidative state and autophagy.

Cardiac stromal cells (CSCs) are the main players in fibrosis. Dysmetabolic conditions (metabolic syndrome-MetS, and type 2 diabetes mellitus-DM2) are strong pathogenetic contributors to cardiac fibrosis. Moreover, modulation of the oxidative state (OxSt) and autophagy is a fundamental function affecting the fibrotic commitment of CSCs, that are adversely modulated in MetSDM2. We aimed to characterize CSCs from dysmetabolic patients, and to obtain a beneficial phenotypic setback from such fibrotic commitment by modulation of OxSt and autophagy. CSCs were isolated from 38 patients, stratified as MetS, DM2, or controls. Pharmacological modulation of OxSt and autophagy was obtained by treatment with trehalose and NOX4NOX5 inhibitors (TREiNOX). Flow-cytometry and real-time quantitative polymerase chain reaction (RT-qPCR) analyses showed significantly increased expression of myofibroblasts markers in MetS-CSCs at baseline (GATA4, ACTA2, THY1CD90) and after starvation (COL1A1, COL3A1). MetS- and DM2-CSCs displayed a paracrine profile distinct from control cells, as evidenced by screening of 30 secreted cytokines, with a significant reduction in vascular endothelial growth factor (VEGF) and endoglin confirmed by enzyme-linked immunoassay (ELISA). DM2-CSCs showed significantly reduced support for endothelial cells in angiogenic assays, and significantly increased H

Perceptions of Dutch general practitioners towards eHealth for patients with type-2 diabetes a qualitative study.

eHealth provides a viable option to facilitate type-2 diabetes mellitus self-management and adherence. To this end, a web-based computer-tailored eHealth programme, My Diabetes Profile (MDP), was developed and implemented in Dutch diabetes care. To fully utilize the potential of eHealth, the reach of effective programmes like MDP should be maximized. Therefore, it is vital to explore perceptions of general practitioners (GPs) regarding eHealth and factors that influence GPs decision to adopt eHealth programmes. To shed light on Dutch GPs perceptions towards eHealth in general and specifically, the adoption of MDP. Interviews were conducted among a heterogeneous sample of 16 Dutch GPs. The interview guide, based on the Diffusion of Innovations Theory, addressed perceptions about eHealth in general, characteristics of MDP, organizational characteristics, and external influences on adoption. Audio-recordings were transcribed and analysed using deductive coding in NVivo. Nearly all GPs used some form of eHealth and listed many benefits and few drawbacks about eHealth. Sometimes, GPs were unaware of what eHealth encompassed programmes resembling MDP were not mentioned. COVID-19 immensely increased eHealth uptake, especially for remote communication. Regarding MDP, the organizational and external influences on adoption were limited, while characteristics of the innovation were deemed more important. GPs expressed benefits of MDP (e.g. uncomplex, user-friendly, tailored) other than attributed to eHealth in general and fewer drawbacks. While GPs opinions about eHealth and MDP were positive, the concept of MDP was relatively unfamiliar. Future research should focus on targeting GPs awareness of eHealth possibilities.

The relationship between fatigue severity and mild cognitive impairment in Saudi patients with type 2 diabetes mellitus.

Type 2 Diabetes Mellitus (T2DM) is a major health issue in Saudi Arabia, with a prevalence of 23.7% in 2015. Several factors contribute to the occurrence of Mild Cognitive Impairment (MCI) and its progression to Alzheimers disease in patients with T2DM. This study assesses MCI and fatigue severity and their relationship in patients with T2DM. Out of the 160 Saudi adults interviewed at the King Khalid University Hospital in Riyadh from October 2019 till March 2020, 80 were known cases of T2DM while the rest were non-diabetic individuals. The Montreal Cognitive Assessment (MoCA) test, Mini Mental State Exam (MMSE) and Fatigue Severity Score (FSS) were used to evaluate MCI and fatigue severity, respectively. According to the MoCA scale, 68.7% diabetic individuals as against 42.5% from the non-diabetic group had MCI. While the FSS showed that 40% of the diabetic group vs 26.3% of the non-diabetic were fatigued. In conclusion, patients with T2DM are at a higher risk of developing MCI.

Neutrophil lymphocyte ratio as useful predictive tool for glycaemic control in type 2 diabetes Retrospective, single centre study in Turkey.

To evaluate the inflammatory cells in the complete blood count test and their relationship with the glycaemic control in type 2 diabetes patients. The retrospective clinical study was conducted at the Department of Family Medicine, Bezmialem Vakif University, Istanbul, Turkey, from January 2015 to June 2016, and comprised adult type 2 diabetes patients data, like complete blood count and biochemical parameters. The data was stratified according to glycated haemoglobin levels <7% in group 1, and >7% in group 2. Data was analysed using SPSS 21. Of the 320 subjects, 172(54%) were in group 1 and 148(46%) in group 2. Overall, there were 106(33%) male and 214(67%) female subjects. The mean age of the sample was 53.6±11.9 years. White blood cell count, neutrophil count and neutrophil-lymphocyte ratios were significantly higher in group 2. Red blood cell count, mean platelet volume, fasting blood glucose, triglyceride, alanine aminotransferase levels were also significantly higher in group 2 (p <0.05). Simple complete blood count test can be used as a cost-effective tool to monitor glycaemic regulation in type 2 diabetes patients.

The anti-diabetic activity of polyphenols-rich vinegar extract in mice via regulating gut microbiota and liver inflammation.

Polyphenols in vinegar are benefit to human health. The purpose of this research was to identify the polyphenols-rich vinegar extract (VE) and evaluate the anti-diabetic mechanisms in vivo. The results showed that 29 polyphenols were identified by UPLC-QTrap-MSMS analysis. 4-Hydroxybenzoic acid, ferulic acid, and ethyl ferulate were the main polyphenols. In addition, VE relieved the symptoms of type 2 diabetes mellitus (T2DM) by down-regulating blood glucose and lipemia. VE reduced inflammation by inhibiting TLR4NF-κB signaling pathway. Furthermore, VE treatment restored gut microbiota dysbiosis (upregulating Bacteroidetes, Lactobacillus, Bifidobacterium, and Bacteroides and downregulating Firmicutes, Proteobacteria, and Enterorhabdus abundances), and increased short chain fatty acids contents in diabetic mice, which participated in anti-diabetic effect of VE by correlation analysis. These findings suggest that VE may be a candidate for T2DM intervention by regulating gut microbiota and inflammation.

A synergistic effect of the triglyceride-glucose index and the residual SYNTAX score on the prediction of intermediate-term major adverse cardiac events in patients with type 2 diabetes mellitus undergoing percutaneous coronary intervention.

The residual SYNTAX score (rSS), a quantitative measure of angiographic completeness of revascularization after percutaneous coronary intervention (PCI), and the triglyceride-glucose index (TyG index), a reliable surrogate marker of insulin resistance, have been regarded as independent predictors of major adverse cardiac events (MACEs) after PCI. Whether a combination of the rSS and the TyG index improves the predictive ability for MACEs in patients with type 2 diabetes mellitus (T2DM) undergoing PCI remains unknown. A total of 633 consecutive patients with T2DM who underwent PCI were included in the present analyses. Patients were stratified according to the optimal cutoff point value of the TyG index, or the rSS determined by receiver‑operating characteristic (ROC) curve analysis. The primary endpoint was the composite of MACEs, including all-cause death, nonfatal myocardial infarction, and unplanned repeat revascularization. Cumulative curves were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of MACEs. The predictive value of the TyG index combined with the rSS was estimated by the area under the ROC curve, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). During a median follow-up of 18.83 months, 99 patients developed MACEs, more frequently in the patients with a higher TyG index or rSS. Multivariate Cox hazards regression analysis revealed that both the TyG index and rSS were independent predictors of MACEs (hazard ratio 1.8004 95% CI 1.2603-2.5718 P 0.0012 1.0423 95% CI 1.0088-1.0769 P 0.0129, respectively). Furthermore, Kaplan-Meier analysis demonstrated that both the TyG index and the rSS were significantly associated with an increased risk of MACEs (log-rank, all P < 0.01). The addition of the rSS and the TyG index to the baseline risk model had an incremental effect on the predictive value for MACE (increase in C-statistic value from 0.660 to 0.732 IDI 0.018 NRI 0.274 all P < 0.01). The TyG index predicts intermediate-term MACE after PCI in patients with T2DM independent of known cardiovascular risk factors. Adjustment of the rSS by the TyG index further improves the predictive ability for MACEs in patients with T2DM undergoing PCI.

Whole genome sequencing analysis to evaluate the influence of T2DM on polymorphisms associated with drug resistance in M. tuberculosis.

Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n 74), and without (n 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed. The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations. The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.

A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes.

The success of glucagon-like peptide-1 (GLP-1) receptor agonists to treat type 2 diabetes (T2D) and obesity has sparked considerable efforts to develop next-generation co-agonists that are more effective. We conducted a randomised, placebo-controlled phase 1b study (ClinicalTrials.gov NCT04466904) to evaluate the safety and efficacy of IBI362 (LY3305677), a GLP-1 and glucagon receptor dual agonist, in Chinese patients with T2D. A total of 43 patients with T2D were enrolled in three cohorts in nine study centres in China and randomised in each cohort to receive once-weekly IBI362 (3.0 mg, 4.5 mg or 6.0 mg), placebo or open-label dulaglutide (1.5 mg) subcutaneously for 12 weeks. Forty-two patients received the study treatment and were included in the analysis, with eight receiving IBI362, four receiving placebo and two receiving dulaglutide in each cohort. The patients, investigators and study site personnel involved in treating and assessing patients in each cohort were masked to IBI362 and placebo allocation. Primary outcomes were safety and tolerability of IBI362. Secondary outcomes included the change in glycated haemoglobin A

Accounting for concurrent antihyperglycemic medication changes in dietary and physical activity interventions A focused literature review.

To summarize methods used to account for antihyperglycemic medication changes in randomized controlled trials evaluating the effect of dietary and physical activity interventions on glycemia among adults with diabetes. Using studies included in two recently published systematic reviews of randomized controlled trials examining the glycemic effects of dietary and physical activity interventions, we evaluated how each study accounted for antihyperglycemic medication changes. Data were analyzed using summary statistics, stratified by the type of intervention studied, and each was assigned a score from 0 to 6 reflecting the strength of medication controls employed. We evaluated 22 physical activity focused and 27 dietary focused articles. Our scoring system yielded a mean concurrent medication adjustment score of 3.96 for the physical activity studies and a score of 1.76 ( We found that randomized controlled trials included in recent systematic reviews of physical activity and dietary interventions did not robustly account or control for changes in antihyperglycemic medications, with physical activity interventions doing so more robustly than dietary interventions. This is a threat to the validity of study findings, as observed glycemic changes may in fact be attributable to imbalances in concurrent medication adjustments between groups.

Gut hormones and reproduction.

Reproduction and metabolism are intricately linked. Gut hormones play key roles in the regulation of body weight and glucose homeostasis, factors that influence the functioning of the hypothalamic-pituitary-gonadal axis and reproductive outcomes. Data from rodent models suggest gut hormones may have direct stimulatory effects on reproductive hormone release. However, the effects of gut hormones on reproductive function in humans are more complex, with possible involvement of direct (e.g. via gut hormone receptor agonism) as well as indirect (e.g. via weight reduction in people with obesity) mechanisms. The use of gut hormone receptor agonists has become an integral part of the management of metabolic diseases (including obesity and type 2 diabetes), with additional indications for their use on the horizon. Future work may identify specific roles for gut hormone receptor agonists in the treatment of reproductive co-morbidities that are increasingly being recognised in people with metabolic diseases.

The cephalic phase of insulin release is modulated by IL-1β.

The initial cephalic phase of insulin secretion is mediated through the vagus nerve and is not due to glycemic stimulation of pancreatic β cells. Recently, IL-1β was shown to stimulate postprandial insulin secretion. Here, we describe that this incretin-like effect of IL-1β involves neuronal transmission. Furthermore, we found that cephalic phase insulin release was mediated by IL-1β originating from microglia. Moreover, IL-1β activated the vagus nerve to induce insulin secretion and regulated the activity of the hypothalamus in response to cephalic stimulation. Notably, cephalic phase insulin release was impaired in obesity, in both mice and humans, and in mice, this was due to dysregulated IL-1β signaling. Our findings attribute a regulatory role to IL-1β in the integration of nutrient-derived sensory information, subsequent neuronally mediated insulin secretion, and the dysregulation of autonomic cephalic phase responses in obesity.

Effects of diabetes on osteocytes.

Better understanding of the mechanisms underlying skeletal dysfunction in the context of diabetes is needed to guide the development of therapeutic interventions to reduce the burden of diabetic fractures. Osteocytes, the master regulators of bone remodeling, have emerged as key culprits in the pathogenesis of diabetes-related skeletal fragility. Both type 1 diabetes and type 2 diabetes cause chronic hyperglycemia that, over time, reduces bone quality and bone formation. In addition to acting as mechanosensors, osteocytes are important regulators of osteoblast and osteoclast activities however, diabetes leads to osteocyte dysfunction. Indeed, diabetes causes the accumulation of advanced glycation end-products and senescent cells that can affect osteocyte viability and functions via increased receptor for advanced glycation endproducts (RAGE) signaling or the production of a pro-inflammatory senescence-associated secretory phenotype. These changes may increase osteocyte-derived sclerostin production and decrease the ability of osteocytes to sense mechanical stimuli thereby contributing to poor bone quality in humans with diabetes. Osteocyte dysfunction exists at the nexus of diabetic skeletal disease. Therefore, interventions targeting the RAGE signaling pathway, senescent cells, and those that inhibit sclerostin or mechanically stimulate osteocytes may alleviate the deleterious effects of diabetes on osteocytes and bone quality.

Establishment of type 2 diabetes mellitus models using streptozotocin after 3 months high-fat diet in Bama minipigs.

In the past twenty years, the number of adults with diabetes has tripled. Most studies have been conducted using rodent models of type 2 diabetes mellitus (T2DM), and the developed drugs have low clinical conversion efficiency. Therefore, it is urgent to establish a more human-like large animal model to explore T2DM pathogenesis and formulate new disease prevention and control strategies. This study was designed to establish and validate a T2DM model using minipigs fed a high-fat or high-cholesterolhigh-fat diet and injected with low-dose streptozotocin (STZ). We examined the influence of the STZ injection timing with a diet high in fat (HFD) compared with one high in cholesterol and fat (HCFD) on the atherosclerotic lesions accelerated by T2DM. Male Bama minipigs (

DPP-4 inhibitor linagliptin ameliorates imiquimod-induced psoriasis-like skin alterations in type 2 diabetic mice by inhibiting the MAPKNF-κB inflammatory pathway.

Studies have shown that the DPP-4 inhibitor was effective in improving skin damage in patients with psoriasis, but the exact mechanism was not known. To investigate the therapeutic effects of linagliptin in mice with type 2 diabetes mellitus (T2DM) with psoriasis and its possible therapeutic mechanisms. A total of 32 dbdb mice and 16 dbm mice were randomly divided into six groups normal group, psoriasis group, diabetes group, diabetes combined with psoriasis group, linagliptin-treated diabetes group, and linagliptin-treated diabetes combined with psoriasis group. The levels of serum fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured the levels of serum FINS were determined by enzyme-linked immunoassay and the insulin resistance index was calculated. Basic parameters of diabetes, Psoriasis Area and Severity Index, histopathology of skin, the expression of interleukin (IL)-17A, IL-23, IL-22, and tumor necrosis factor (TNF)-α, and expression levels of measuring p-ERK, p-MAPK and p-nuclear factor kappa B (NF-κB) in skin tissues were measured. After treatment with linagliptin, insulin resistance, and TC and TG levels were reduced in mice with T2DM and psoriasis (p < .05). Moreover, the degree of epidermal tissue thickening, number of keratinized layers, and inflammatory cell infiltration were also reduced (p < .05), as well as the expression levels of inflammatory factors TNF-α, IL-1β, IL-17A, IL-23, and p-P38P38, p-ERKERK, p-P65P65 proteins (p < .05). Linagliptin significantly reduced the extent of skin lesions and skin inflammation. The underlying mechanism of this compound may be related to the inhibition of MAPKNF-κB inflammatory pathways and the consequential improvement of insulin resistance.Significance Statement In this study, we evaluated the therapeutic effect of the DPP-4 inhibitor linagliptin using a murine model of type 2 diabetes combined with psoriasis, and its potential mechanisms of action were further explored. The results of this study will help to uncover the pathogenesis of type 2 diabetes and psoriasis and, more importantly, provide a theoretical basis for the search for safe and effective drugs in the treatment of this specific patient population.

Membrane-Catalyzed Aggregation of Islet Amyloid Polypeptide Is Dominated by Secondary Nucleation.

Type II diabetes is characterized by the loss of pancreatic β-cells. This loss is thought to be a consequence of membrane disruption, caused by the aggregation of islet amyloid polypeptide (IAPP) into amyloid fibrils. However, the molecular mechanisms of IAPP aggregation in the presence of membranes have remained unclear. Here, we use kinetic analysis to elucidate the aggregation mechanism of IAPP in the presence of mixed zwitterionic and anionic lipid membranes. The results converge to a model in which aggregation on the membrane is strongly dominated by secondary nucleation, that is, the formation of new nuclei on the surface of existing fibrils. The critical nucleus consists of a single IAPP molecule, and anionic lipids catalyze both primary and secondary nucleation, but not elongation. The fact that anionic lipids promote secondary nucleation implies that these events take place at the interface between the membrane and existing fibrils, demonstrating that fibril growth occurs at least to some extent on the membrane surface. These new insights into the mechanism of IAPP aggregation on membranes may help to understand IAPP toxicity and will be important for the development of therapeutics to prevent β-cell death in type II diabetes.

Insulin resistance and skeletal health.

Bone fragility is a complication of type 2 diabetes (T2D), and insulin resistance is suspected to contribute to diabetes-related bone deficits. This article provides an overview of emerging clinical research involving insulin resistance and bone health by summarizing recent publications, identifying existing knowledge gaps, and suggesting next steps for this evolving field of research. Clinical studies in children and adults report greater bone density in people with increased insulin resistance, but these associations are often attenuated when adjusting for body size. Advancements in bone imaging methods allow for assessment of nuanced characteristics of bone quality and strength that extend beyond standard bone mineral density assessment methods. For example, several recent studies focusing on lumbar spine trabecular bone score, a relatively new measure of trabecular bone quality from dual-energy X-ray absorptiometry, have reported generally consistent inverse associations with insulin resistance. Longitudinal studies using advanced imaging methods capable of evaluating trabecular bone microstructure and strength, such as high-resolution peripheral quantitative computed tomography, are lacking. Studies in younger individuals are sparse, but emerging data suggest that peak bone mass attainment might be threatened by diabetes progression, and increased visceral fat, suppressed muscle-bone unit, advanced glycation end-products, sedentary lifestyle, and poor diet quality might contribute to diabetes effects on bone. Prospective studies during the transition from adolescence to young adulthood are required. Insulin resistance is a main feature of T2D, which is suspected to contribute to subclinical diabetes-related threats to bone health. Future clinical studies should focus on the critical years surrounding peak bone mass and peak bone strength attainment using contemporary imaging techniques.

Type 2 diabetes an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers.

This study sought to identify potential pharmacogenetic associations of selected enzymes and transporters with type 2 diabetes (T2D). In addition, pharmacogenomic profiles, concentrations of asymmetric dimethylarginine (ADMA) or kidney injury molecule-1 (KIM-1), and several covariates were investigated. Whole blood was collected from 63 patients, with 32 individuals with T2D. A pharmacogenomic panel was used to assay genetic profiles, and biomarker ELISAs were run to determine subject concentrations of ADMA and KIM-1. Additive genetic modeling with multiple linear and logistic regressions were performed to discover potential SNPs-outcome associations using PLINK. Ten SNPs were found to be significant (p<0.05) depending on the inclusion or exclusion of covariates. Of these, four were found in association with the presence of T2D, rs2231142, rs1801280, rs1799929, and rs1801265 depending on covariate inclusion or exclusion. Regarding ADMA, one SNP was found to be significant without covariates, rs1048943. Five SNPs were identified in association with KIM-1 and T2D in the presence of covariates, rs12208357, rs34059508, rs1058930, rs1902023, and rs3745274. Biomarker concentrations were not significantly different in the presence of T2D. This exploratory study found several SNPs related to T2D further research is required to validate and understand these relationships.

A roadmap to achieve pharmacological precision medicine in diabetes.

Current pharmacological treatment of diabetes is largely algorithmic. Other than for cardiovascular disease or renal disease, where sodium-glucose cotransporter 2 inhibitors andor glucagon-like peptide-1 receptor agonists are indicated, the choice of treatment is based upon overall risks of harm or side effect and cost, and not on probable benefit. Here we argue that a more precise approach to treatment choice is necessary to maximise benefit and minimise harm from existing diabetes therapies. We propose a roadmap to achieve precision medicine as standard of care, to discuss current progress in relation to monogenic diabetes and type 2 diabetes, and to determine what additional work is required. The first step is to identify robust and reliable genetic predictors of response, recognising that genotype is static over time and provides the skeleton upon which modifiers such as clinical phenotype and metabolic biomarkers can be overlaid. The second step is to identify these metabolic biomarkers (e.g. beta cell function, insulin sensitivity, BMI, liver fat, metabolite profile), which capture the metabolic state at the point of prescribing and may have a large impact on drug response. Third, we need to show that predictions that utilise these genetic and metabolic biomarkers improve therapeutic outcomes for patients, and fourth, that this is cost-effective. Finally, these biomarkers and prediction models need to be embedded in clinical care systems to enable effective and equitable clinical implementation. Whilst this roadmap is largely complete for monogenic diabetes, we still have considerable work to do to implement this for type 2 diabetes. Increasing collaborations, including with industry, and access to clinical trial data should enable progress to implementation of precision treatment in type 2 diabetes in the near future.

Low molecular weight NGF mimetic GK-2 normalizes the parameters of glucose and lipid metabolism and exhibits a hepatoprotective effect on a prediabetes model in obese Wistar rats.

Signs of metabolic syndrome and prediabetes preceding type 2 diabetes are modelled in an experiment using a high-fat diet (HFD). The aim of this work was to study the effect of a low molecular weight systemically active nerve growth factor mimetic, compound GK-2 (hexamethylenediamide bisN-monosuccinyl-L-glutamyl-L-lysine), on indicators of abdominal obesity, basal blood glucose level, glucose tolerance, cholesterol and triglyceride blood levels, as well as the morphological structure of the liver in male Wistar rats fed a HFD. Rats were divided into three groups one of them received standard food (control) and two others were fed a HFD containing 45% fat, 35% carbohydrates and 20% protein, with a total caloric value of 516 kcal100 g, over 12 weeks. Starting from the ninth week, for the next 4 weeks, one of the HFD groups was treated orally with saline whilst the other group was treated orally with GK-2 at a dose of 5 mgkg. GK-2 was found to reduce the basal glycaemia level and improve glucose tolerance, as well as to reduce the blood level of cholesterol by 30% and that of triglycerides by 28% in comparison with the saline-treated HFD animals. GK-2 reduced the degree of abdominal obesity to the level of the healthy animals and eliminated morphological abnormalities in the liver caused by the HFD. The results of the study determine the feasibility of further GK-2 research as a potential agent for prediabetes treatment.

Comparative Effects of Embryonic Metformin Exposure on Wild and Laboratory-Spawned Fathead Minnow (

Metformin is routinely detected in aquatic ecosystems because of its widespread use as a treatment for Type 2 diabetes. Laboratory studies have shown that exposure to environmentally relevant concentrations of metformin can alter metabolic pathways and impact the growth of early life stage (ELS) fish however, it is unknown whether these effects occur in wild populations. Herein, we evaluate whether findings from laboratory studies are representative and describe the relative sensitivities of both populations. Duplicate exposures (0, 5, or 50 μgL metformin) were conducted using wild- and lab-spawned fathead minnow (

Diabetes and cancer Optimising glycaemic control.

Diabetes and cancer are both common and increasingly prevalent conditions, but emerging epidemiological evidence confirms that the risk of developing a number of common cancers is increased in those with type 2 diabetes. The risk of cancer in type 1 diabetes is less clearly defined, and therefore this review focuses on type 2 diabetes. Emerging evidence also supports an influence of diabetes on outcomes of cancer treatment. However, this relationship is bi-directional, with cancer and its treatment impacting on glucose control, whereas there is also emerging evidence indicating that diabetes care can deteriorate after a cancer diagnosis. Despite these clear links, there is a lack of evidence to guide clinicians in how to manage patients with diabetes during their cancer treatment. Although recent UK guidelines have started to address this, with the development of guidance for the management of hyperglycaemia in cancer, there is a clear need for wider guidance on the management of multi-morbidity during cancer, including diabetes and obesity, to incorporate nutritional management. We have therefore undertaken a narrative review of the evidence of links between type 2 diabetes and cancer incidence and outcomes, and discuss the challenges to diabetes care during cancer treatment.

Insulin Response to Oral Glucose and Cardiometabolic Disease A Mendelian Randomization Study to Assess Potential Causality.

Mendelian randomization (MR) suggests that postprandial hyperinsulinemia (unadjusted for plasma glucose) increases BMI, but its impact on cardiometabolic disease, a leading cause for mortality and morbidity in people with obesity, is not established. Fat distribution i.e., increased centripetal andor reduced femoro-gluteal adiposity, is causally associated with and better predicts cardiometabolic disease than BMI. We therefore undertook bidirectional MR to assess the effect of corrected insulin response (CIR) (insulin 30 min after a glucose challenge adjusted for plasma glucose) on BMI, waist-to-hip ratio (WHR), leg fat, type 2 diabetes (T2D), triglyceride (TG), HDL, liver fat, hypertension (HTN), and coronary artery disease (CAD) in people of European descent. Inverse variance-weighted MR suggests a potential causal association between increased CIR and increased BMI (b 0.048 ± 0.02, P 0.03), increased leg fat (b 0.029 ± 0.012, P 0.01), reduced T2D (b -0.73 ± 0.15, P 6 × 10-7, odds ratio OR 0.48 95% CI 0.36-0.64), reduced TG (b -0.07 ± 0.02, P 0.003), and increased HDL (b 0.04 ± 0.01, P 0.006) with some evidence of horizontal pleiotropy. CIR had neutral effects on WHR (b 0.009 ± 0.02, P 0.69), liver fat (b -0.08 ± 0.04, P 0.06), HTN (b -0.001 ± 0.004, P 0.7, OR 1.00 95% CI 0.99-1.01), and CAD (b -0.002 ± 0.002, P 0.48, OR 0.99 95% CI 0.81-1.21). T2D decreased CIR (b -0.22 ± 0.04, P 1.3 × 10-7), with no evidence that BMI, TG, HDL, liver fat, HTN, and CAD modulate CIR. In conclusion, we did not find evidence that increased CIR increases cardiometabolic disease. It might increase BMI with favorable fat distribution, reduce T2D, and improve lipids.

Association between serum manganese levels and diabetes in Chinese adults with hypertension.

Manganese (Mn) is an essential trace metal element that is associated with diabetes however, the results of previous studies are inconsistent. Furthermore, few studies have been conducted in a hypertensive population. The purpose of this study is to explore the relationship between manganese and diabetes in a population with hypertension. A cross-sectional study was conducted, including 2575 hypertensive individuals from 14 provinces in China. Serum manganese concentrations were measured by the inductively coupled plasma mass spectrometry (ICP-MS) method. And logistic regression models were used to analyze the association between serum manganese and the risk of diabetes. The prevalence of diabetes was 27.0% in this hypertensive population. In logistic regression models, the odds ratios (95% confidence interval) for diabetes in tertile subgroups were 1.40 (1.12, 1.76) and 1.32 (1.05, 1.65) for tertiles 1 and tertiles 3, respectively, compared to tertile 2 (reference). Additionally, an interaction between sex and manganese was observed. The odds ratios (95% confidence interval) for diabetes were 1.29 (0.95, 1.75) and 0.96 (0.70, 1.31) for tertiles 1 and tertiles 3 among males, and 1.44 (1.01, 2.04) and 1.81 (1.29, 2.55) for tertiles 1 and tertiles 3 among females, respectively, compared to tertile 2. In conclusion, a U-shaped association between serum manganese and diabetes was observed in a Chinese population with hypertension, and the association was modified by sex.

Recent Insights of Metformin on Hepatocellular Carcinoma (HCC).

Metformin is an oral hypoglycemic drug, which was the first option used to treat type 2 diabetes mellitus due to its high efficacy and low cost. Recently, it has drawn attention among researchers due to new-found antitumor effect. Growing evidence showed that metformin could inhibit cancer progression especially in hepatocellular carcinoma, and several clinical trials are underway. However, the underlying mechanisms of the inhibition of hepatocellular carcinoma remain to be further explored and clarified. Herein, we reviewed the latest findings of how metformin acts against hepatocellular carcinoma and the proposed mechanisms. In addition, we included related preclinical trials, along with the limitations and perspectives of its treatment in hepatocellular carcinoma, providing novel ideas for researches to conquer hepatocellular carcinoma.

NOS3 rs1799983 and rs2070744 polymorphisms and their association with advanced chronic kidney disease and coronary heart disease in Canarian population with type 2 diabetes.

Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. Cross-sectional case-control study. Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes estimated glomerular filtration rate (eGFR) <30 mLmin1.73 m A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD OR 2.17 (95% CI 1.17-4.00), p0.014 and for comparison to healthy controls OR 1.61 (1.03-2.52), p0.036. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983. NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

Platelet indices in patients with type 2 diabetes mellitus undergoing percutaneous coronary intervention.

Platelet indices change in relation to cardiovascular risk factors, including type 2 diabetes mellitus (T2DM). An increase of platelet indices over time in patients undergoing percutaneous coronary intervention (PCI) could be a predictor of mortality.The objective of this study was to assess differences in platelet indices in patients with and without T2DM undergoing PCI, prior and more than one month after the procedure. In this retrospective observational study, patients undergoing PCI were included. Data were extracted from PCI Registry of the Emergency Institute for Cardiovascular Diseases and Transplantation of Tirgu Mures, Romania. Of the 718 patients included in the study, 222 (30.9%) had T2DM 61% of patient underwent PCI for SCAD, the rest for NSTE-ACS or STEMI. Prior to PCI, MPV, PDW and P-LCR were not higher in T2DM patients irrespective of the indication for PCI. At a follow-up time of 69 (46-98) days, platelet indices were not different between TD2M and T2DM-, except from MPV (11.0 Platelet indices were not higher in patients with T2DM undergoing PCI, but we observed an important variation in platelet indices in diabetics after STEMI related PCI.

Risk Factors of Ischemia Reperfusion Injury After PCI in Patients with Acute ST-Segment Elevation Myocardial Infarction and its Influence on Prognosis.

To explore the risk factors of ischemia reperfusion injury (IRI) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and its influence on prognosis. The clinical data of 80 patients with STMEI undergoing PCI in our hospital from June 2020 to June 2021 were collected. According to whether IRI occurred after PCI, STMEI patients were divided into IRI group and non-IRI group. The basic information, clinical characteristics, examination parameters and other data of all patients were collected, and the prognosis of the two groups was observed. Risk factors were analyzed by fitting binary Logistic regression model. The survival prognosis was analyzed by Kaplan-Meier survival curve. Logistic regression analysis showed that type 2 diabetes mellitus (T2DM), pre-hospital delay time (PHD) and door-to-balloon expansion time (DTB) were the influencing factors of IRI in patients with STMEI ( T2DM, PHD and DTB were the influencing factors of IRI in patients with STMEI, and IRI will not reduce the prognosis of patients.

Atrial fibrillation prevalence and predictors in patients with diabetes a cross-sectional screening study.

Prevalence of atrial fibrillation (AF) and diabetes is increasing worldwide. Diabetes is a risk factor for AF and both increase stroke risk. Previous AF screening studies have recruited highrisk patient groups, but not with diabetes as the target group. This study aims to determine whether people with diabetes have a higher prevalence of AF than the general population and investigate whether determinants, such as diabetes duration or diabetes control, add to AF risk. In a cross-sectional screening study, patients with diabetes were recruited via their GP surgeries or a diabetes centre. A 30-second single-lead electrocardiogram (ECG) was recorded using the Kardia

Cardiovascular effects of intensive lifestyle intervention in adults with overweightobesity and type 2 diabetes according to body weight time in range.

We aimed to assess whether the cardiovascular effects of intensive lifestyle intervention (ILI) vary for those who can maintain the lower body weight after weight loss through ILI. In the secondary analysis of the Look AHEAD trial, we identified the status of weight loss for the participants in the ILI arm based on body weight time in range (TIR). These participants were allocated to three groups according to body weight TIR 0% ( During a median of 9·5 years of follow-up, participants with TIR of >50% to 100% can effectively maintain their body weight after weight loss through ILI participants with TIR of 0% or >0% to 50% do not achieve or maintain weight loss. Compared with the corresponding matched participants in the DSE arm, participants with TIR of >50% to 100% in the ILI arm had a 45% lower risk of the primary outcome (HR 0·55, 95% CI 0·40-0·76), and no significant effects were found on the risk of the primary outcome in participants with TIR of 0% (HR 1·12, 95% CI 0·86-1·46) or >0% to 50% (HR 1·14, 95% CI 0·85-1·52). In adults with overweightobesity and type 2 diabetes, ILI might help in lowering the risk of cardiovascular events when the lower body weight is maintained after weight loss. None.

Serum Activities of Ferritin Among Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients.

Background Diabetes mellitus (DM) is a metabolic disorder characterized by the cells inefficient utilization of blood glucose. DM occurs in two types type 1 DM (T1DM) and type 2 DM (T2DM). DM results in increased blood sugar levels attributed to the non-functioning of the insulin-producing islet cells of the pancreas (type 1 DM) and insulin resistance, among other causes. Despite the initiation of treatment, in some people, diabetes remains uncontrolled and, over some time, could cause damage to other organs of the body, including the eyes, heart, and kidneys, among others. Recently, it was observed that iron metabolism and increased activity of serum ferritin (hyperferritinemia) could influence the development of T2DM. This study aims to assess the activities of ferritin among controlled and uncontrolled T2DM patients and compare them with the control group who were non-diabetic. Methods The study included 30 controlled and uncontrolled T2DM patients and an equal number of controls. The study was conducted between September and October 2021, and all patients included were those attending the General Medicine outpatient department attached to the RVM Institute of Medical Sciences and Research Centre, Siddipet, Telangana, South India. Blood glucose activities were estimated by the glucose oxidase-peroxidase (GOD-POD) method using the Randox Daytona plus analyzer, and serum ferritin was measured by the chemiluminescence method using the Beckmann Coulter Access 2 instrument. Results The mean age of the cases and the controls was 56.5 years and 46.7 years, respectively. Serum ferritin activities among people with controlled diabetes (73.3±56.6 ngml) (p0.0003) and uncontrolled diabetes (269.8±347.1 ngml) (p0.0006) varied significantly as compared to the controls (40.853±15.55). Glucose activities among controls (82.9±7.4 mgdl), controlled T2DM patients (120.9±28.6 mgdl), and uncontrolled T2DM patients (316.06±145.41 mgdl) also showed significant differences. Conclusion Hyperferritinemia is evident among uncontrolled T2DM patients. However, increased serum ferritin activities were also noted among controlled T2DM patients as compared to normal activities observed in the non-diabetic control group.

Occurrence of mild cognitive impairment with hyperinsulinaemia in Africans with advanced type 2 diabetes mellitus.

There is paucity of information on the prevalence of mild cognitive impairment (MCI) among individuals with type 2 diabetes mellitus (T2DM) in sub-Saharan Africa, including Nigeria. In addition, the role of hyperinsulinaemia in the development of MCI needs further investigation. This study sought to assess cognition and hyperinsulinaemia, with the associated characteristics in patients with advanced T2DM. Cognition was assessed using Montreal cognitive assessment test (MoCA), while fasting plasma insulin was measured using an ELISA kit. Sixty one diabetic subjects and 32 non-diabetic controls, matched for age, gender and level of education were studied. The diabetics had MCI while the controls had normal cognitive function. About 88.5% of the diabetic subjects had MCI, in contrast with only 50% of the non-diabetic controls. The most significantly affected cognitive domains among the diabetics were executive function, naming, attention, abstraction and delayed recall. Among the diabetics, MCI correlated with age, weight and body mass index (BMI) and in addition, age and weight found to be significant predictors of MCI. Plasma insulin concentration among the diabetics (16.24 ± 13.5 µIUml) was more than twice that of the controls (7.59 ± 2.9 µIUml). Hyperinsulinaemia among the diabetics correlated with weight, BMI, blood pressure and fasting blood sugar (FBS). Glycated haemoglobin and FBS levels were higher among diabetics compared with the controls. In conclusion, Africans with advanced T2DM show multi-domain MCI

Time-specific associations of wearable sensor-based cardiovascular and behavioral readouts with disease phenotypes in the outpatient setting of the Chronic Renal Insufficiency Cohort.

Patients with chronic kidney disease are at risk of developing cardiovascular disease. To facilitate out-of-clinic evaluation, we piloted wearable device-based analysis of heart rate variability and behavioral readouts in patients with chronic kidney disease from the Chronic Renal Insufficiency Cohort and controls (n 49). Time-specific partitioning of heart rate variability readouts confirm higher parasympathetic nervous activity during the night (mean RR at night 14.4 ± 1.9 ms vs. 12.8 ± 2.1 ms during active hours n 47, analysis of variance (ANOVA) q 0.001). The α2 long-term fluctuations in the detrended fluctuation analysis, a parameter predictive of cardiovascular mortality, significantly differentiated between diabetic and nondiabetic patients (prominent at night with 0.58 ± 0.2 vs. 0.45 ± 0.12, respectively, adj.

Adherence to General Diabetes and Foot Care Processes, with Prompt Referral, Are Associated with Amputation-Free Survival in People with Type 2 Diabetes and Foot Ulcers A Scottish National Registry Analysis.

To compare different packages of care across care providers in Scotland on foot-related outcomes. A retrospective cohort study with primary and secondary care electronic health records from the Scottish Diabetes Registry, including 6,845 people with type 2 diabetes and a first foot ulcer occurring between 2013 and 2017. We assessed the association between exposure to care processes and major lower extremity amputation and death. Proportional hazards were used for time-to-event univariate and multivariate analyses, adjusting for case-mix characteristics and care processes. Results were expressed in terms of hazard ratios with 95% confidence intervals. 2,243 (32.7%) subjects had a major amputation or death. Exposure to all nine care processes at all ages (HR 0.63 95% CI 0.58-0.69 Strict adherence to a standardised package of general diabetes care before foot ulceration, timely foot care after ulceration, and specific treatment pathways were associated with longer major amputation-free survival among a large cohort of people with type 2 diabetes in Scotland, with a larger impact on older age groups.

Biomarkers Predictive for In-Hospital Mortality in Patients with Diabetes Mellitus and Prediabetes Hospitalized for COVID-19 in Austria An Analysis of COVID-19 in Diabetes Registry.

This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate ( Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients.