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Oral innate immunity in patients with type 2 diabetes mellitus in a tertiary hospital in Ibadan Nigeria a cross-sectional study.

diabetes mellitus is associated with a high prevalence of oral infections. However, it is unclear how diabetes impacts oral innate antimicrobial proteins. This study evaluated salivary lysozyme and histatins, two major innate antimicrobial proteins, in patients with diabetes and non-diabetic controls. a cross-sectional study where salivary lysozyme and histatins were measured alongside plasma glucose levels. Values of the salivary proteins were compared between the two groups their association with glucose levels was also established using correlation and regression analysis. one hundred and fifty-one participants were recruited for this study, 85 (56.3%) of them had type 2 diabetes mellitus with a median fasting plasma glucose of 108.8 mgdl (IQR 91.2-134.8) while the remaining 66 (43.7%) healthy non-diabetic controls had a median random plasma glucose of 101 mgdl (IQR 89-112). The median salivary lysozyme was 32.5 ngml (IQR 25.0-39.6) in the group with diabetes and 36.4 ngml (IQR 31.4-42.1 p0.01) in the non-diabetic control group. The median salivary histatins was 9.2 ngml (IQR 7.6 -10.2) in the group with diabetes and 14.7 ngml (IQR12.8-16.5 p<0.001) in the non-diabetic control group. Salivary lysozyme (r -0.127 p 0.163) and histatins (r -0.025 p 0.424) were both negatively correlated with plasma glucose levels, and logistic regression showed that patients with diabetes are more likely to have lower levels of salivary lysozyme (0.957 p0.013) and histatins (0.527 p<0.001). patients with diabetes had reduced levels of salivary lysozyme and histatins, this could provide an insight into the associated high oral infection rates.

Chinese herbal medicine combined with western medicine for the treatment of type 2 diabetes mellitus with hyperuricemia A systematic review and meta-analysis.

Hypoglycemic Encephalopathy Manifesting with Cortical Hemichorea-Hemiballismus Syndrome A Case Report.

Hyper-hypoglycemic states are rare but well-established causes of hyperkinetic movements, including chorea and ballismus, usually associated with brain lesions in the basal ganglia. We report a case of hemichorea-hemiballismus (HCHB) syndrome that developed after a severe hypoglycemic episode in a 71-year-old man with poorly controlled type 2 diabetes mellitus. Uncommonly, brain MRI showed contralateral cortical-subcortical T2 and T2-FLAIR-hyperintense frontoparietal lesions, with cingulate gyrus involved, while the basal ganglia were unaffected. In patients with hypoglycemic encephalopathy associated with cortical lesions, the long-term prognosis is usually poor. Nevertheless, in our patient, the dyskinesias and the cerebral lesions progressively regressed by achieving good glycemic control. After four and 12 months, the patients neurological examination was normal. To our knowledge, this is the first evidence of hypoglycemic etiology of cortical HCHB syndrome, supporting recent theories that cortical circuitries may independently contribute to the pathogenesis of chorea and ballismus. This is also the first report of cingulate gyrus involvement in hypoglycemic encephalopathy. Finally, this case may indicate that a subset of patients with cortical lesions due to hypoglycemia could present a good clinical outcome, likely depending on the size of the lesions and the duration and severity of the hypoglycemic episode.

Accelerometer-derived physical activity and sedentary behaviors in individuals with newly diagnosed type 2 diabetes A cross-sectional study from the Danish nationwide DD2 cohort.

Habitual physical activity behaviors of individuals with new-onset type 2 diabetes are largely unknown. We aimed to investigate accelerometer-derived physical activity behaviors in individuals with newly diagnosed type 2 diabetes. We also examined sociodemographic and health-related correlates of a high-risk physical activity profile. This cross-sectional study used data from 768 participants enrolled in an intervention study nested within the Danish Centre for Strategic Research in Type 2 diabetes (DD2) cohort. Physical activity was assessed by 24-h dual monitor accelerometry. Prevalence ratios of having a high-risk physical activity profile were estimated using Poisson regression adjusted for age and sex. Study participants spent on average 9.7 (25th and 75th percentiles, 8.3 11.1) hoursday sitting, walked for 1.1 (0.8 1.6) hoursday and accumulated 4,000 (2,521 5,864) stepsday. Still, 62% met the recommendations for physical activity. Characteristics associated with a high-risk physical activity profile (observed in 24.5% of participants) included older age, higher body mass index (BMI), unemployment, retirement, comorbidities, and current smoking. Hence, participants aged 60-69, 70-79 and 80 years had prevalence ratios of 2.12 (95% CI 1.31 3.42), 1.99 (1.18 3.34) and 3.09 (1.42 6.75) for a high-risk activity profile, respectively, versus participants <50 years. BMI values of 30-39 and 40 were associated with 1.83 (1.06 3.15) and 3.38 (1.88 6.05) higher prevalence ratios compared to normal-weight. Unemployment or retirement was associated with 1.62 (1.09 2.41) and 2.15 (1.37 3.39) times higher prevalence ratios, compared to individuals in the working force. Having a Charlson Comorbidity Index score of 1-2 or 3 was associated with 1.36 (1.03-1.79) and 1.90 (1.27-1.84) higher prevalence ratios, while current smoking was associated with a prevalence ratio of 1.72 (1.25 2.35) compared to never smokers. This study shows that 62% of individuals with newly diagnosed type 2 diabetes met the recommendations for physical activity. Still, the majority of participants were also highly sedentary and accumulated very few daily steps, emphasizing the need for focusing on both increasing physical activity and reducing sedentary behaviors in the prevention of diabetes-related complications. Individuals with a high-risk physical activity profile were characterized by more obesity, socioeconomic inequalities, advanced age and comorbidities.Trial registration number NCT02015130.

Assessment of type 2 diabetes mellitus patients behavioral characteristics associated with integrated treatment and prevention services in community health centers in China.

The purpose of this study was to describe behavioral characteristics of type 2 diabetes mellitus (T2DM) patients, identify homogeneous clusters, and explore factors affecting behaviors associated with integrated treatment and prevention (ITP) services for T2DM in community health centers in China. A convenient sampling method was employed at a community health center between January and July 2022 in Nanjing. A total of 354 patients completed the self-reported questionnaires. After performing a Cluster Analysis to create a profile of participants behaviors, a multiple linear regression analysis was conducted to explore the correlations between T2DM patients characteristics and their behaviors associated with ITP services. 316 T2DM patients with a mean age of 72.09 years (SD 5.96) were included. The behavior profiles of patients associated with ITP services were clustered into Lower ( Patients behaviors associated with ITP services for T2DM were moderately good (the score rate was 63.98%). Of all the behaviors, complication examination and public health service utilization scored the lowest and, as such, may warrant further research. The clustering of patients behaviors tends to be polarization, distributed at the upper and lower ends of the behavior spectrum. It is necessary to develop and implement targeted interventions for different groups to improve T2DM patients behaviors associated with ITP services.

Lipid Management in Korean People With Type 2 Diabetes Mellitus Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement.

Dyslipidemia in patients with diabetes is an important treatment target as a modifiable risk factor for cardiovascular disease (CVD). Although the primary treatment goal for dyslipidemia is to control low-density lipoprotein cholesterol (LDL-C), achieving this goal remains suboptimal according to recent studies. It is important to set the target goal for LDL-C control based on an accurate risk assessment for CVD. Here, we summarize the latest evidence on lipid management in patients with diabetes and present a consensus of the Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis on the treatment goals of LDL-C according to the duration of diabetes, presence of CVD, target organ damage, or major cardiovascular risk factors. In patients with type 2 diabetes mellitus (T2DM) and CVD, an LDL-C goal of <55 mgdL and a reduction in LDL-C level by 50% or more from the baseline is recommended. For the primary prevention of CVD in patients with T2DM with a duration of diabetes ≥10 years, major cardiovascular risk factors, or target organ damage, an LDL-C goal of <70 mgdL is recommended. In patients with T2DM with a duration of diabetes <10 years and no major cardiovascular risk factors, an LDL-C goal of <100 mgdL is recommended.

Prevalence of type 2 diabetes complications and its association with diet knowledge and skills and self-care barriers in Tabriz, Iran A cross-sectional study.

Diabetes can lead to multiple complications that can reduce the quality of life, impose additional costs on the healthcare systems and ultimately lead to premature death. Proper self-care in diabetic patients can impede or delay the onset of diabetes complications. This study aimed to investigate diabetes complications and their association with diet knowledge, skills, and self-care barriers. This was a cross-sectional study. A total of 1139 patients with Type 2 Diabetes Mellitus (T2DM) referring to health centers in Tabriz, Iran, were included from January to July 2019. Data were collected using two questionnaires (1) a sociodemographic questionnaire and (2) a Personal Diabetes Questionnaire (PDQ). Data were analyzed using SPSS software version 22. In this study, 76.1% of patients had at least one complication, and 30.2% had a history of hospitalization due to diabetes complications during the past year. Approximately 49% and 43% were diagnosed with high blood pressure and hyperlipidemia, respectively. Cardiovascular disease was the most common diabetes complication (15.9%) and the cause of hospitalization (11.01%) in patients with diabetes. Barriers to diet adherence, blood glucose monitoring, and exercise were significantly associated with self-reported diabetes complications ( This study indicated that the prevalence of diabetes complications was higher among patients with more barriers to self-care. In light of these findings, taking appropriate measures to reduce barriers to self-care can prevent or delay the onset of diabetes complications.

Altered dynamic functional architecture in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) can accelerate cognitive decline and even dementia so that the underlying mechanism deserves further exploration. In the resting state, brain function is still changing dynamically. At present, it is still unknown whether the dynamic functional connectivity (dFC) between various brain regions is in a stable state. It is necessary to interpret brain changes from a new perspective, that is, the stability of brain architecture. In this study, we used a fixed dynamic time scale to explore the stability of dynamic functional architecture in T2DM, then the dynamic effective connectivity (dEC) was used to further explain how information flows through dynamically fluctuating brain architecture in T2DM. Two brain regions with decreased stability were found including the right supra-marginal gyrus (SMG) and the right median cingulate gyrus (MCG) in T2DM subjects. The dEC variation has increased between the left inferior frontal gyrus (IFG) and the right MCG. The direction of causal flow is from the right MCG to the left IFG. The combination of stability and dEC can not only show the stability of dynamic functional architecture in brain but also reflect the fluidity of brain information, which is an innovative and interesting attempt in the field of neuroimaging. The changes of dynamic architecture in T2DM patients may present an innovative perspective and explanation for their cognitive decline.

Molecular Pathways of Diabetic Kidney Disease Inferred from Proteomics.

Diabetic kidney disease (DKD) affects an estimated 20-40% of type 2 diabetes patients and is among the most prevalent microvascular complications in this patient population, contributing to high morbidity and mortality rates. Currently, changes in albuminuria status are thought to be a primary indicator of the onset or progression of DKD, yet progressive nephropathy and renal impairment can occur in certain diabetic individuals who exhibit normal urinary albumin levels, emphasizing the lack of sensitivity and specificity associated with the use of albuminuria as a biomarker for detecting diabetic kidney disease and predicting DKD risk. According to the study, a non-invasive method for early detection or prediction of DKD may involve combining proteomic analytical techniques such second generation sequencing, mass spectrometry, two-dimensional gel electrophoresis, and other advanced system biology algorithms. Another category of proteins of relevance may now be provided by renal tissue biomarkers. The establishment of reliable proteomic biomarkers of DKD represents a novel approach to improving the diagnosis, prognostic evaluation, and treatment of affected patients. In the present review, a series of protein biomarkers that have been characterized to date are discussed, offering a theoretical foundation for future efforts to aid patients suffering from this debilitating microvascular complication.

A Nomogram for Predicting Vision-Threatening Diabetic Retinopathy Among Mild Diabetic Retinopathy Patients A Case-Control and Prospective Study of Type 2 Diabetes.

This study aims to develop a nomogram for predicting vision-threatening diabetic retinopathy (VTDR) in type 2 diabetes mellitus (T2DM) with mild non-proliferative diabetic retinopathy (NPDR) patients. In case-control analysis, 440 patients with mild NPDR or VTDR were enrolled to identify predictors and develop a nomogram. In the prospective cohort, 120 T2DM patients with mild NPDR were enrolled for external validation. Sensitivity, specificity, and area under the receiver operating characteristic (AUC) were calculated to evaluate the predictive performance of the nomogram. In case-control analysis, 2-h C-peptide (OR 0.85, 95% CI 0.75 to 0.95, p 0.006), sural nerve conduction impaired (SNCI) (mildly OR 2.18, 95% CI 1.10 to 4.33, p 0.026 moderatelyseverely 3.66, 95% CI 1.74 to 7.70, p < 0.001) and UACR (microalbuminuria OR 2.37, 95% CI 1.25 to 4.48, p 0.008 macroalbuminuria 4.02, 95% CI 1.61 to 10.06, p 0.003) were identified as independent predictors. The concordance index of the prediction nomogram was 0.76 in the training set. In the test set, sensitivity, specificity, and AUC were 84.8%, 60.6%, and 0.73, respectively. In the prospective cohort, median follow-up period was 42 months, and 15 patients (12.5%) developed VTDR. Sensitivity, specificity, and AUC of prediction were 66.7%, 89.5%, and 0.75, respectively. Introducing 2-h C-peptide, UACR, and SNCI, the nomogram demonstrated a good discriminatory power for predicting risk of VTDR in mild NPDR individuals.

Deep Sea Water Inhibited Pancreatic β-Cell Apoptosis and Regulated Glucose Homeostasis by Affecting Lipid Metabolism in DbDb Mice.

Deep sea water (DSW) is a natural resource rich in minerals, which participates in biological processes such as energy metabolism, regulates serum glucose and lipids levels, and has a certain protective effect on endocrine and metabolism-related diseases. Studies have shown that the improvement of glucose tolerance in diabetic mice by DSW may be associated with the protective effect on the structure and function of pancreatic islets, and the specific mechanism is still unclear. Other studies have shown that long-term exposure to high concentrations of fatty acids can lead to apoptosis and dysfunction of pancreatic β-cell, increasing the risk of type 2 diabetes mellitus (T2DM). Down-regulation of plasma fatty acid levels may reduce pancreatic β-cell dysfunction, thereby improving glucose homeostasis. Understanding the specific mechanism of DSW regulating blood glucose is of great significance for its clinical application. In the present study we used dbdb mice as a T2DM model and treated mice with deep ocean mineral concentration (DOMC, a commercial product of DSW) for 4 and 12 weeks. Basic information, serum biochemical indicators, and pathological tissues were gathered for exploration. The dbdb mice treated with 4 weeks DOMC (dbdbDOMC) showed decreased plasma cholesterol and triglyceride levels. Tests implied that in adipose tissues, the dbdbDOMC groups lipolysis process was inhibited, and the β-fatty acid oxidation process was promoted. Besides, DOMC reduced lipogenesis and encouraged β-oxidation in the liver, as a result, improved fatty liver in dbdb mice. Further measurements showed DOMC improved glucose homeostasis slightly in dbdb animals after a 12-week treatment by preventing pancreatic β-cell apoptosis. DOMC inhibited pancreatic β-cell apoptosis and regulated glucose homeostasis in dbdb mice by lowering the lipid levels via regulation of fatty acid β-oxidation, lipolysis, and lipogenesis processes.

Serum Pentosidine is Associated with Cardiac Dysfunction and Atherosclerosis in T2DM.

The purpose of this paper is to investigate the relationship between serum pentosidine levels and cardiac function and vascular disease in diabetic patients, and to provide a new reference indicator for the early detection of diabetic cardiovascular complications. This was a cross-sectional study. One hundred and twenty-two patients with type 2 diabetes were grouped by LVEF quartiles to compare the differences between their clinical data and serum pentosidine levels. Also, the correlation between serum pentosidine and clinical indicators was assessed. The effect of serum pentosidine on cardiac function and vascular stiffness was analyzed by multiple stepwise regression. Serum pentosidine levels were higher in patients with LVEF ≤57%. Serum pentosidine levels were positively correlated with waist-to-hip ratio, hemoglobin, AIP, baPWV, LVESD, and ARD, and negatively correlated with LVEF. Low serum pentosidine was associated with increased LVESD high pentosidine was significantly associated with increased ARD, high AIP and high baPWV. The results suggest that serum pentosidine, a member of AGEs, may reflect cardiac remodeling and dysfunction as well as atherosclerosis.

Association Between Uric Acid to HDL Cholesterol Ratio and Diabetic Complications in Men and Postmenopausal Women.

Previous studies have implicated the uric acid to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) was associated with type 2 diabetes. However, the association between UHR and diabetes-related vascular damages is still unclear. The total of 4551 patients with type 2 diabetes from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai study (METAL study) were enrolled. UHR was calculated as uric acid to HDL-C ratio. Cardiovascular disease (CVD) was defined as previously diagnosed with stroke, coronary heart disease, or peripheral arterial disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate ≤60 mLmin1.73 m UHR was positively correlated with CVD (OR 1.28, 95% CI 1.02-1.61) and CKD (OR 1.78, 95% CI 1.39-2.27) after adjusting for all confounders. No association was found between UHR and DR. In stratified analyses, UHR was predominantly correlated with CVD in diabetic patients with age older than 65 (OR 1.41, 95% CI 1.08-1.85), female (OR 1.43, 95% CI 1.06-1.94) and BMI≥24kgm Our study reported a positive association between the UHR and diabetic-related vascular complications in men and postmenopausal women. The relationship between the UHR and DR seems to be uncertain and requires further investigation. And no significant interaction effect was observed between the UHR and all subgroup variables in CVD and CKD risk.

Metabolic Characteristics of Gestational Diabetes Mellitus and the Effects on Pregnancy Outcomes.

To describe the metabolic characteristics of gestational diabetes mellitus (GDM) and assess their effects on perinatal outcomes. A two-center nested case‒control study was designed, including 192 pregnant women with GDM and 191 pregnant women with normal glucose tolerance (NGT). Serum glucose and insulin concentrations based upon the 75 g oral glucose tolerance test (OGTT) were measured. Several indices were calculated to describe the metabolic characteristics of the subjects. The relationship between glucose metabolism parameters and pregnancy outcomes was evaluated using stepwise linear regression and binary logistic regression. Compared with the NGT group, the GDM group showed significantly higher fasting and postprandial glucose parameters but significantly lower fasting and postprandial insulin responses. Meanwhile, the GDM group had significantly lower HOMA-β, DI and ISI Beta cell dysfunction rather than insulin resistance determines the occurrence of GDM in the central Chinese population. Women with predominant insulin secretion defects had a similar risk of adverse perinatal outcomes to women with NGT. Our study provided a basis for the selection of glucose metabolism monitoring indicators useful for the prevention of adverse perinatal outcomes.

Clinical Characteristics and Surgical Outcomes of Complications of Proliferative Diabetic Retinopathy in Young versus Older Patients with Type 2 Diabetes.

Proliferative diabetic retinopathy (PDR) is a leading vision-threatening disease. In this study, we investigated the clinical features of PDR and the surgical outcomes of its complications in patients with type 2 diabetes (T2D). We retrospectively reviewed the medical data of patients with T2D who underwent vitrectomy for PDR between January 2016 and June 2021. The patients were divided into two groups by age (young patients, < 45 years older patients, ≥ 45 years). There were 149 eyes (100 patients) in the young patient group and 315 eyes (256 patients) in the older patient group. The proportion of males and the proportion of patients requiring binocular surgery were much higher in the young patient group than in the older patient group ( In this retrospective study, young patients who underwent vitrectomy for PDR had more severe clinical characteristics before vitrectomy. However, vitrectomy (combined with cataract surgery when necessary) achieved better final visual outcomes in young patients than in older patients with T2D.

Adiponectin Paradox More Evident in Non-Obese Than in Obese Patients with Diabetic Microvascular Complications.

Adiponectin is generally regarded as a beneficial molecule, protecting against insulin resistance and atherosclerosis, and its serum levels are low in individuals with obesity as well as in those with type 2 diabetes (T2DM). However, several clinical studies have shown associations between high adiponectin values and major health concerns. These conflicting findings are termed the adiponectin paradox. Similarly, these paradoxical adiponectin elevations were observed in patients with diabetic microvascular complications. This cross-sectional study aimed to identify differences in factors, including adiponectin, related to diabetic vascular complications between non-obese and obese patients. Study patients with T2DM were non-obese (n197) or obese (n197), matched by a propensity score model adjusted with age and gender. Independent factors for each of the microvascular complications were determined using multivariate logistic regression analyses. The prevalence of nephropathy was high in obese T2DM patients. In addition to long diabetes duration, elevated adiponectin was a common characteristic of patients with microvascular complications. Logistic regression analyses for microvascular complications revealed adiponectin to be highly related to retinopathy (odds ratio OR, 1.138 95%confidence intervals CI, 1.004-1.289, p<0.001), nephropathy (OR, 1.192 CI, 1.077-1.319, p<0.001) and neuropathy (OR, 1.217 CI, 1.071-1.384, p<0.001), in non-obese patients. In contrast, the association between adiponectin values and complications was modest in obese patients. Adiponectin regulation in response to vascular damage differed between non-obese and obese patients, suggesting that adiponectin regulation is compromised by fat accumulation. Assuming that paradoxical elevation of adiponectin in vascular damage is a compensatory response, we speculate that responsive upregulation might be insufficient in obese patients. These newly-recognized differences in adiponectin values might lead to novel insights into adiponectin regulation and our understanding of the adiponectin paradox.

Addressing the Continuum of Dysglycaemia and Vascular Complications in Prediabetes and Type 2 Diabetes Need for Early and Intensive Treatment.

The onset of type 2 diabetes increases the risk of vascular complications and death. We know now that that this risk begins long before the diabetes diagnosis. Prediabetes and type 2 diabetes are not separate entities in practice and exist within a continuum of dysglycaemia and vascular risk that increases in severity over time. This excess risk requires early intervention with lifestyle therapy supported with pharmacologic antidiabetic therapy, intensified promptly where necessary throughout the duration of the diabetes continuum. Metformin is an evidence-based treatment for preventing prediabetes and improves cardiovascular outcomes in people with type 2 diabetes from diagnosis onwards. Newer agents (SGLT2 inhibitors and GLP-1 agonists) are appropriate for people presenting with type 2 diabetes and significant cardiovascular comorbidity. Additional therapies should be used without delay to achieve patients individualised HbA1c goals and to minimise cardiovascular risk.

Investigation of the Correlation Between the PolymorphismExpression Level of RANTES and Its Receptor CCR5 Gene Promoter and Type 2 Diabetes Mellitus.

This study aimed to explore relationship among RANTES -28 (rs2280788) CG polymorphism or CCR5 59029 (rs1799987) AG polymorphism, level of self-expression, and type 2 diabetes mellitus (T2DM). Clinical data were collected from 92 subjects with normal blood glucose (NC) and 97 patients with T2DM (DM). CCR5 levels on the surface of monocytelymphocyte and plasma RANTES levels were detected by flow cytometry. TaqMan real-time fluorescent quantitative PCR was used to detect genetic polymorphisms of RANTES rs2280788 and CCR5 rs1799987. There were no significant differences in frequencies of CCR5 rs1799987 genotype and AG allele and frequencies of RANTES rs2280788 genotype and CG allele, between subjects in NC and DM group ( RANTES -28 (rs2280788) CG polymorphism or CCR5 59029 (rs1799987) AG polymorphism may not be associated with T2DM of Han nationality in Kunming and cannot affect RANTES and CCR5 expression. RANTES and CCR5 levels may be related to T2DM but may also be affected by age, blood lipids, HbA1c, diabetes course, drugs, and other factors.

Reduced Serum Levels of Klotho are Associated with Mild Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

The study objective was to investigate the serum levels of Klotho in patients with type 2 diabetes mellitus (T2DM) who had moderate cognitive impairment (MCI) and those without MCI and to determine its prediction of MCI in older patients with T2DM. Patients with diabetes were examined for MCI in 292 cases (using the Montreal Cognitive Assessment MoCA score). Biomarkers and biochemical parameter data were accumulated. Comparing T2DM patients with MCI (91 patients) and without MCI (101 patients), patients with MCI considerably reduced serum Klotho levels were observed. In all 292 hospitalized patients, serum Klotho levels were negatively correlated with age (r-0.184, P0.002), body mass index (BMI) (r-0.151, P0.010), glycosylated hemoglobin (HbA1c) (r-0.197, P0.001), creatinine (r-0.178, P0.002), and C-reactive protein (CRP) (r-0.319, P<0.001). On the other hand, it is positively correlated with education (r0.319, P<0.001) and high-density lipoprotein cholesterol (HDL-C) (r0.272, P<0.001). Considering the findings of the multivariate logistic regression models, patients with type 2 diabetes who had reduced levels of serum Klotho (OR0.987, 95% CI0.980-0.994 P<0.001), lower HDL-C, increased levels of HbA1c, creatinine, and CRP, and limited years of formal education and a longer duration of T2DM, increase the risk of developing MCI. The results showed that diabetic patients with MCI have lower serum Klotho levels than diabetic patients without MCI. It might be possible to do a more extensive population-based prospective investigation to confirm the correlation between serum Klotho levels and cognitive impairment or dementia.

Managing Severe Hypoglycaemia in Patients with Diabetes Current Challenges and Emerging Therapies.

Hypoglycaemia is common in patients with diabetes mellitus and is a limiting factor for achieving adequate glycaemic control. In the vast majority of cases, hypoglycaemia develops due to the imbalance between food intake and insulin injections. As recurrent hypoglycaemia leads to significant morbidity and mortality, the recognition and immediate treatment of hypoglycaemia in diabetic patients is thus important. In the last 20 years, the introduction of improved insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), and sensor-augmented pump therapy have all made significant improvements in helping to reduce and prevent hypoglycaemia. In terms of treatment, the American Diabetes Association recommends oral glucose as the first-line treatment option for all conscious patients with hypoglycaemia. The second line of treatment (or first line in unconscious patients) is the use of glucagon. Novel formulations of glucagon include the nasal form, the Gvoke HypoPen which is a ready-to-deliver auto-injector packaged formulation and finally a glucagon analogue, Dasiglucagon. The Dasiglucagon formulation has recently been approved for the treatment of severe hypoglycaemia. It is a ready-to-use, similar to endogenous glucagon and its potency is also the same as native glucagon. It does not require reconstitution before injection and therefore ensures better compliance. Thus, significant improvements including development of newer insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), sensor-augmented pump therapy and novel formulations of glucagon have all contributed to reducing and preventing hypoglycaemia in diabetic individuals. However, considerable challenges remain as not all patients have access to diabetes technologies and to the newer glucagon formulations to help reduce and prevent hypoglycaemia.

A Patient-Centered Self-Management Intervention to Improve Glycemic Control, Self-Efficacy and Self-Care Behaviors in Adults with Type 2 Diabetes Mellitus A SPIRIT Compliant Study Protocol for Randomized Controlled Trial.

The rising burden of type 2 diabetes mellitus (DM) and its associated complications is affecting the functional capacity of the individuals, their quality of life and demand for healthcare services with significant economic impact on health care systems and the national economies. Given the enormous health and economic impact, preventing type 2 DM progression and reducing the risk of complications require immediate attention. Evidence from western countries suggests that self-management can slow the progression of type 2 DM and minimize the risk of major complications lowering health-care costs. Effective self-management, however, demands patients confidence and their full commitment to perform self-care tasks necessitating a patient-centered approach. This study aims to test the efficacy of a patient-centered self-management intervention to improve glycemic control, self-efficacy and self-care behaviors in adults with type 2 DM. The study will be carried out as a parallel arm, randomized, controlled trial in four public tertiary care hospitals in Faisalabad, Pakistan. A total of 612 patients with type 2 DM will be recruited and randomly assigned to two groups a control and an intervention group. The intervention group will receive a patient-centered self-management intervention for eight weeks duration. Subjects will be followed up for three months. The primary outcome will be glycemic control (HbA1c), and secondary outcome variables will include self-efficacy and self-care behaviors all measured at three points in time (baseline, at the end of intervention and at three months follow-up). This randomized controlled trial will provide critical information about the efficacy of patient-centered self-management intervention in improving HbA1c, self-efficacy and self-care behaviors. If successful, this evidence-based care intervention may be provided to all DM patients by updating hospital policies. NIH US National Library of Medicine clinicaltrials.gov Identifier NCT05491252, Shifa Tameer e Millat University Protocol Record 335-21. Registration date August 08, 2022. Recruitment began April 21, 2022. Recruitment completed July 27, 2022. URL httpwww.clinicaltrials.gov.

The Impact of Insulin Staging in the Context of Pharmaceutical Care on Patients with Type 2 Diabetes Mellitus.

The problem of polypharmacy and the nature of the disease make patients with type 2 diabetes mellitus highly vulnerable to drug therapy problems, especially those who are on insulin therapy. Despite this challenge, reaching the desired clinical outcome and using an appropriate insulin regimen are also considered a controversial issue among clinicians. The current study is designed to explore the impact of insulin staging regimens in the context of pharmaceutical care on patients with type 2 diabetes mellitus. This study is a randomized interventional comparative study of a few groups. It was conducted at the Diabetes and Endocrine Centre in Sulaymaniyah City in Iraq from January to August 2022. Patients with T2DM who were on insulin therapy were enrolled in this trial. The participants were divided into two groups, the interventional and non-interventional groups. The insulin regimen was modified, and pharmaceutical care process was performed for the intervention group. Drug therapy problems (DTPs) and clinical parameters were monitored both groups over the course of six months. A total of 67 patients with T2DM on insulin were included in this study, and of them, 73% were females, with a mean age of 57.34 ± 7.825 years. The groups were randomly divided into intervention and non-intervention groups. After six months of applying insulin staging in the context of pharmaceutical care, FPG (Mean Diff. 72.25, 95% CI of diff. 20.44 to 124.1), HbA1c (Mean Diff. 2.087, 95% CI of diff. 1.151 to 3.023) and DTP were significantly improved in the intervention group. Implementing the insulin staging approach within the context of the pharmaceutical care process showed a significant impact on controlling plasma glucose levels.

Glucose variability in maintenance hemodialysis patients with type 2 diabetes Comparison of dialysis and nondialysis days.

Hemodialysis (HD) induces several physiological changes that can affect plasma glucose levels in patients with diabetes and in turn their glycemic control. Studies using continuous glucose monitoring (CGM) to assess glucose variations on dialysis days compared with nondialysis days report conflicting results. Here, we used CGM to examine glucose variations induced by HD in patients with type 2 diabetes. Patients with type 2 diabetes undergoing maintenance HD were included. CGM (Ipro2®, Medtronic) was performed at baseline and Week 4, 8, 12, and 16 for up to 7 days at each visit. CGM profiles on days where participants received HD were compared with days without HD using a linear mixed model. Twenty-seven patients were included. The median number of CGM days performed was 8 (interquartile range IQR 6-10) for dialysis days and 16 (IQR 12-17) for nondialysis days. The median sensor glucose was 9.4 (95% confidence interval CI 8.8-10.2) mmolL on dialysis days compared with 9.5 (95% CI 8.9-10.2) mmolL on nondialysis days (p 0.58). Nocturnal mean sensor glucose was higher on dialysis days compared with nondialysis days 8.8 (95% CI 8.0-9.6) mmolL versus 8.4 (95% CI 7.7-9.2) mmolL (p 0.029). Similar median sensor glucose values were found for days on and off HD. Nocturnal glucose levels were modestly increased on dialysis days. Our findings indicate that antidiabetic treatment does not need to be differentiated on dialysis versus nondialysis days in patients with type 2 diabetes undergoing maintenance HD.

Scale-up of a chronic care model-based programme for type 2 diabetes in Belgium a mixed-methods study.

Type 2 diabetes (T2D) is an increasingly dominant disease. Interventions are more effective when carried out by a prepared and proactive team within an organised system - the integrated care (IC) model. The Chronic Care Model (CCM) provides guidance for its implementation, but scale-up of IC is challenging, and this hampers outcomes for T2D care. In this paper, we used the CCM to investigate the current implementation of IC in primary care in Flanders (Belgium) and its variability in different practice types. Belgium contains three different primary-care practice types monodisciplinary fee-for-service practices, multidisciplinary fee-for-service practices and multidisciplinary capitation-based practices. Disproportional sampling was used to select a maximum of 10 practices for each type in three Flemish regions, leading to a total of 66 practices. The study employed a mixed methods design whereby the Assessment of Chronic Illness Care (ACIC) was complemented with interviews with general practitioners, nurses and dieticians linked to the 66 practices. The ACIC scores of the fee-for-service practices - containing 97% of Belgian patients - only corresponded to basic support for chronic illness care for T2D. Multidisciplinary and capitation-based practices scored considerably higher than traditional monodisciplinary fee-for-service practices. The region had no significant impact on the ACIC scores. Having a nurse, being a capitation practice and having a secretary had a significant effect in the regression analysis, which explained 75% of the variance in ACIC scores. Better-performing practices were successful due to clear role-defining, task delegation to the nurse, coordination, structured use of the electronic medical record, planning of consultations and integration of self-management support, and behaviour-change intervention (internally or using community initiatives). The longer nurses work in primary care practices, the higher the chance that they perform more advanced tasks. Besides the presence of a nurse or secretary, also working multidisciplinary under one roof and a capitation-based financing system are important features of a system wherein IC for T2D can be scaled-up successfully. Belgian policymakers should rethink the role of paramedics in primary care and make the financing system more integrated. As the scale-up of the IC varied highly in different contexts, uniform roll-out across a health system containing multiple types of practices may not be successful.

The effects of soymilk plus probiotics supplementation on cardiovascular risk factors in patients with type 2 diabetes mellitus a randomized clinical trial.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular diseases. This study aimed to assess the effects of soymilk plus probiotics co-administration on cardiovascular risk factors in T2DM patients. One hundred patients with T2DM (aged 40-75 years old) were randomly assigned into 4 groups (soymilk probiotics supplement, soymilk placebo, conventional milk placebo, and probiotics supplement) for 6 weeks. Standard protocols were followed for the collection of fasting blood samples, dietary intakes, and anthropometric measurements. It was shown that soymilk probiotics consumption significantly decreased diastolic blood pressure (DBP) (p 0.001), triglycerides (TG) (P < 0.001), total cholesterol (TC) (p < 0.01), and insulin (P < 0.003) levels and significantly increased high-density lipoprotein cholesterol (HDL-C) (P 0.002) levels. Soymilk placebo administration significantly decreased DBP (p 0.01), insulin (p 0.006), and TG (p 0.001) levels and significantly increased HDL-C (p 0.03) levels. A significant decrease in insulin (p 0.003) and systolic blood pressure (SBP) (p 0.01) levels and an increase in HDL-C (p 0.04) levels were observed after supplementation with probiotics. Findings from between-group comparisons showed a significant decrease in SBP levels in the probiotics supplement group compared to conventional milk group (p < 0.05). Soymilk and probiotics consumption might improve some cardiovascular risk factors in patients with T2DM. However, possible synergic effects while consumption of soymilk plus probiotics supplement didnt show in this study which warranted further research.

The trajectory of osteoblast progenitor cells in patients with type 2 diabetes and the predictive model for their osteogenic differentiation ability.

The fate of osteoprogenitor cells along with the progression of type 2 diabetes (T2DM) and factors determining the fate of those cells remains to be elucidated. This cross-sectional study included 18 normoglycemic, 27 prediabetic, and 73 T2DM to determine osteogenic differentiation across the continuum of dysglycemia and to construct a model to predict the fate of osteoprogenitor cells. This study demonstrated a preserved osteogenic differentiation ability of peripheral blood-derived mononuclear cells (PBMC) isolated from normoglycemic and prediabetic but a progressive decline in their osteogenic differentiation during the progression of T2DM. The rate of osteogenic differentiation rapidly declined by 4-7% annually during the first 10 years of diabetes and then slowed down. A predictive model composed of three independent risk factors, including age, duration of diabetes, and glomerular filtration rate, demonstrated an AuROC of 0.834. With a proposed cut-off of 21.25, this model had 72.0% sensitivity, 87.5% specificity, and 78.9% accuracy in predicting the fate of osteoprogenitor cells. In conclusion, this study provided a perspective on the osteogenic differentiation ability of the osteoprogenitor cells across a continuum of dysglycemia and a predictive model with good diagnostic performance for the prediction of the fate of osteoprogenitor cells in patients with T2DM.

Pancreatic microexons regulate islet function and glucose homeostasis.

Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and their abnormal function causes diabetes or hypoglycaemia. Here we uncover a conserved programme of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding protein SRRM3 and represent a subset of the larger neural programme that are particularly sensitive to SRRM3 levels. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in human and rat beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, mice harbouring mutations in Srrm3 display defects in islet cell identity and function, leading to hyperinsulinaemic hypoglycaemia. Importantly, human genetic variants that influence SRRM3 expression and IsletMIC inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk. Taken together, our data identify a conserved microexon programme that regulates glucose homeostasis.

Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice.

Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development. Tcf7l2 was selectively ablated in the liver of C57BL6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout KO mice Alb-CreTcf7l2 Alb-CreTcf7l2 In mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL. RNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.govgeoqueryacc.cgiaccGSE162449 ).

Exercise and inactivity as modifiers of beta cell function and type 2 diabetes risk.

Exercise is beneficial for the prevention and management of metabolic diseases such as obesity and type 2 diabetes, while the cessation of regular exercise or physical activity (PA) can lead to metabolic derangements that drive these diseases. Adaptations to the insulin secreting pancreatic b-cells are an important benefit of exercise, while less is known on how exercise cessation affects these cells. The aim of this review is to highlight the known impacts that exercise and exercise cessation have on b-cell function, with a focus on the evidence from studies examining glucose-stimulated insulin secretion (GSIS) using gold standard techniques. Potential mechanisms by which the b-cell adapts to exercise, including exerkine and incretin signaling, autonomic nervous system signaling and changes in insulin clearance, will also be explored and areas for future research highlighted.

Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a complex, familial, polygenetic metabolic condition. The Rotterdam criteria are commonly used to diagnose PCOS. Lifestyle changes are the first-line treatment of PCOS. Treatment options for menstrual irregularities and hirsutism are based on the clinical goals and preferences of the patient. Along with treating the symptoms of PCOS, it is essential to screen and treat the comorbid conditions commonly associated with PCOS, including type 2 diabetes mellitus, obesity, nonalcoholic fatty liver disease, hyperlipidemia, obstructive sleep apnea, anxiety, depression, infertility, and vitamin D deficiency.

Effect of once weekly dulaglutide for juvenile type 2 Diabetes mellitus and obesity in Korea a Pilot Study.

To investigate the effects and side effects of once weekly dulaglutide treatment for type 2 diabetes mellitus (T2DM) in patients under the age of 18 years in Korea. From the Eulji University Hospital database, we identified all patients under the age of 18 years diagnosed with T2DM and treated with dulaglutide from January 1, 2017 to July 31, 2022. We identified five patients under the age of 18 years treated with dulaglutide for T2DM management. Their mean (SD) age was 16.6 (0.5) years. Four (80%) patients were female. The mean (SD) body mass index was 29.4 kgm2 (5.1 kgm2), and the mean (SD) age at diagnosis was 15.2 (1.6) years. Four among them were treated previously with metformin alone or with insulin. Four patients were treated with 1.5 mg dulaglutide and one with 0.7 mg dulaglutide. The mean (SD) HbA1c at baseline was 10.0% (2.2%), at three months of treatment 6.5% (1.5%), and at one year after treatment 6.7% (1.4%), with significant difference. At baseline, the mean (SD) bodyweight was 79.7 kg (13.3 kg), at three months after treatment 80.2 kg (14.0 kg), and at one year after treatment 81.1 kg (15.3 kg), with no significant difference. Use of once weekly dulaglutide for juvenile T2DM had very good glycemic control, with little side effects and good adherence, indicating the potential of dulaglutide as a promising therapeutic agent in this age group. Nationwide studies are warranted to confirm these results.

Exploring the role of lipoprotein(a) in cardiovascular diseases and diabetes in Chinese population.

A high level of lipoprotein (a) in the plasma has been associated with a variety of cardiovascular diseases and is considered to be an independent predictor of some other diseases. Based on recent studies, the concentration levels of Lp(a) in the Chinese population exhibit a distinctive variation from other populations. In the Chinese population, a high level of Lp(a) indicates a higher incidence of revascularization, platelet aggregation, and thrombogenicity following PCI. Increased risk of atherosclerotic cardiovascular disease (ASCVD) in Chinese population has been linked to higher levels of Lp(a), according to studies. More specifically, it has been found that in Chinese populations, higher levels of Lp(a) were linked to an increased risk of coronary heart disease, severe aortic valve stenosis, deep vein thrombosis in patients with spinal cord injuries, central vein thrombosis in patients receiving hemodialysis, and stroke. Furthermore, new and consistent data retrieved from several clinical trials also suggest that Lp (a) might also play an essential role in some other conditions, including metabolic syndrome, type 2 diabetes and cancers. This review explores the clinical and epidemiological relationships among Lp(a), cardiovascular diseases and diabetes in the Chinese population as well as potential Lp(a) underlying mechanisms in these diseases. However, further research is needed to better understand the role of Lp(a) in cardiovascular diseases and especially diabetes in the Chinese population.

Does housing temperature influence glucose regulation and muscle-fat crosstalk in mice

The robustness of scientific results is partly based on their reproducibility. Working with animal models, particularly in the field of metabolism, requires to avoid any source of stress to rule out a maximum of bias. Housing at room temperature is sufficient to induce thermal stress activating key thermogenic organs such as brown adipose tissue (BAT) and skeletal muscle. BAT covers most of the non-shivering thermogenesis in mice and burns a variety of fuels such as glucose and lipids. A high prevalence of BAT is associated with a strong protection against type 2 diabetes risk in humans, implying that BAT plays a key role in glucose homeostasis. However, thermal stress is poorly and inconsistently considered in experimental research. This thermal stress can significantly impede interpretation of phenotypes by favoring compensatory signaling pathways. Indeed, various studies revealed that thermoneutrality is essential to study metabolism in mice in order to reach a suitable level of humanization. In this review, we briefly discuss if and how ambient temperature influence blood glucose homeostasis through BAT and muscle-fat crosstalk.

Hypoxia has been identified as a major factor in the pathogenesis of adipose tissue inflammation, which is a hallmark of obesity and obesity-linked type 2 diabetes mellitus. In this study, we have investigated the impact of hypoxia (1% oxygen) on the physiology and metabolism of 3T3-L1 adipocytes, a widely used cell culture model of adipose. Specifically, we applied parallel labeling experiments, isotopomer spectral analysis, and

Development and validation of risk prediction models for new-onset type 2 diabetes in adults with impaired fasting glucose.

To develop and validate sex-specific risk prediction models based on easily obtainable clinical data for predicting 5-year risk of type 2 diabetes (T2D) among individuals with impaired fasting glucose (IFG), and generate practical tools for public use. The data used for model training and internal validation came from a large prospective cohort (N18,384). Two independent cohorts were used for external validation. A two-step approach was applied to screen variables. Coefficient-based models were constructed by multivariate Cox regression analyses, and score-based models were subsequently generated. The predictive power was evaluated by the area under the curve (AUC). During a median follow-up of 7.55 years, 5697 new-onset T2D cases were identified. Predictor variables included age, body mass index, waist circumference, diastolic blood pressure, triglycerides, fasting plasma glucose, and fatty liver. The proposed models outperformed five existing models. In internal validation, the AUCs of the coefficient-based models were 0.741 (95% CI 0.723-0.760) for men and 0.762 (95% CI 0.720-0.802) for women. External validation yielded comparable prediction performance. We finally constructed a risk scoring system and a web calculator. The risk prediction models and derived tools had well-validated performance to predict the 5-year risk of T2D in IFG adults.

Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin a multicentre, open-label, randomised, phase 2 study.

The burden of daily basal insulins often causes hesitancy and delays in the initiation of insulin therapy. Basal insulin Fc (BIF, insulin efsitora alfa), designed for once-weekly administration, is a fusion protein combining a novel single-chain insulin variant with a human immunoglobulin G (IgG) Fc domain. In this study, we explored the safety and efficacy of BIF in people with type 2 diabetes who had been previously treated with basal insulin. For this phase 2, 44-site (clinical research centres and hospitals), randomised, open-label, comparator-controlled, 32-week study in the USA, Puerto Rico, and Mexico, we enrolled participants with type 2 diabetes. Eligible participants had to be adults (aged ≥18 years) and to have been treated with basal insulin and up to three oral antidiabetic medicines. Participants were randomly assigned (111) to subcutaneous administration of BIF (BIF treatment group 1 BIF-A1 or 2 BIF-A2) or insulin degludec. Randomisation was stratified by country, baseline HbA Between Nov 15, 2018 and Feb 18, 2020, 399 participants were enrolled and randomised to BIF-A1 (n135), BIF-A2 (n132), or degludec (n132) 202 (51%) were female and 197 (49%) were male. 379 were analysed for the primary outcome (BIF-A1 n130 BIF-A2 n125 degludec n124). Mean HbA1c change from baseline to week 32, the primary outcome, was -0·6% (SE 0·1%) for BIF-A1 and BIF-A2. Degludec achieved a change from baseline of -0·7% (0·1%). The pooled BIF analysis achieved non-inferiority versus degludec for the treatment difference in HbA1c (0·1% 90% CI -0·1 to 0·3). The hypoglycaemia (≤3·9 mmolL or ≤70 mgdL) event rates (hypoglycaemia events per patient per year) in the BIF groups were 25% lower than those in the degludec group (treatment ratio BIF-A1 vs degludec was 0·75 0·61-0·93 and BIF-A2 vs degludec was 0·74 0·58-0·94). BIF was well tolerated treatment-emergent adverse events were similar across groups. Weekly BIF achieved a similar efficacy compared with degludec despite higher fasting glucose targets in the BIF groups. Higher fasting glucose targets and lower glucose variability might have contributed to lower hypoglycaemia rates for BIF compared with degludec. These findings support continued development of BIF as a once-weekly insulin treatment for people with diabetes. Eli Lilly and Company.

Risk Amplifiers for Vascular Disease and CKD in South Asians When Intrinsic β-Cell Dysfunction Meets a High-Carbohydrate Diet.

South Asians, comprising almost one fourth of the world population, are at higher risk of type 2 diabetes mellitus, hypertension, cardiovascular disease, and CKD compared with other ethnic groups. This has major public health implications in South Asia and in other parts of the world to where South Asians have immigrated. The interplay of various modifiable and nonmodifiable risk factors confers this risk. Traditional models of cardiometabolic disease progression and CKD evaluation may not be applicable in this population with a unique genetic predisposition and phenotype. A wider understanding of dietary and lifestyle influences, genetic and metabolic risk factors, and the pitfalls of conventional equations estimating kidney function in this population are required in providing care for kidney diseases. Targeted screening of this population for metabolic and vascular risk factors and individualized management plan for disease management may be necessary. Addressing unhealthy dietary patterns, promoting physical activity, and medication management that adheres to cultural factors are crucial steps to mitigate the risk of cardiovascular disease and CKD in this population. In South Asian countries, a large rural and urban community-based multipronged approach using polypills and community health workers to decrease the incidence of these diseases may be cost-effective.

Fatty acid binding protein 1 (FABP1) and fatty acid binding protein 2 (FABP2) as a link between diabetic nephropathy and subclinical atherosclerosis in children and adolescents with type 1 diabetes.

Diabetic nephropathy is a major cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). Fatty acid binding proteins (FABP1 and FABP2) play a role in the development and progression of chronic kidney disease including type 2 diabetes mellitus. We assessed serum FABP1 and FABP2 levels in children and adolescents with T1DM as potential markers for diabetic nephropathy and their relation to carotid intima media thickness (CIMT). Sixty patients with T1DM were divided into 2 groups according to the presence of nephropathy and compared with 30 healthy controls. CIMT, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), urinary albumin creatinine ratio (UACR), fasting lipid profile and serum FABP1 and FABP2 levels were assessed. FABP1 and FABP2 levels were significantly higher among type 1 diabetic patient with and without nephropathy compared with healthy controls with the highest levels among patients with nephropathy (p < 0.001). There were significant positive correlations between FABP1 and FABP2 and each of systolic blood pressure, CIMT, FBG, HbA1c and total cholesterol among T1DM patients. FABP1 was negatively correlated to glomerular filtration rate. Multivariable linear regression analysis showed that systolic blood pressure, CIMT, FBG and HbA1c were the significant independent variables related to FABP1 levels in type 1 diabetic patients with nephropathy. ROC curve analysis was performed to determine the cutoff value of FABP1 and FABP2 that could detect nephropathy. FABP1 and FABP2 levels are elevated in children and adolescents with T1DM and could represent a link between diabetic nephropathy and subclinical atherosclerosis.

Interleukin-4 reduces insulin secretion in human islets from healthy but not type-2 diabetic donors.

Type 2 diabetes (T2D) is associated with low-grade inflammation. Here we investigate if the anti-inflammatory cytokine interleukin-4 (IL-4) affects glucose-stimulated insulin secretion (GSIS) in human islets from non-diabetic (ND) and type-2 diabetic (T2D) donors. We first confirmed that GSIS is reduced in islets from T2D donors. Treatment with IL-4 for 48 h had no further effect on GSIS in these islets but significantly reduced secretion in ND islets. Acute treatment with IL-4 for 1 h had no effect on GSIS in ND islets which led us to suspect that IL-4 affects a slow cellular mechanism such as gene transcription. IL-4 has been reported to regulate miR-378a-3p and, indeed, we found that this microRNA was increased with IL-4 treatment. However, overexpression of miR-378a-3p in the human beta cell line EndoC-βH1 did not affect GSIS. MiR-378a-3p is transcribed from the same gene as peroxisome proliferator-activated receptor gamma co-activator 1 beta (PCG-1β) and we found that IL-4 treatment showed a clear tendency to increased gene expression of PCG-1β. PCG-1β is a co-activator of peroxisome proliferator-activated receptor gamma (PPARγ) and, the gene expression of PPARγ was also increased with IL-4 treatment. Our data suggests that the protective role of IL-4 on beta cell survival comes at the cost of lowered insulin secretion, presumably involving the PPARγ-pathway.

Replacement substance P reduces cardiac fibrosis in monkeys with type 2 diabetes.

Type 2 diabetes mellitus (T2DM)-associated cardiac fibrosis contributes to heart failure. We previously showed that diabetic mice with cardiomyopathy, including cardiac fibrosis, exhibit low levels of the neuropeptide substance P exogenous replacement of substance P reversed cardiac fibrosis, independent of body weight, blood glucose and blood pressure. We sought to elucidate the effectiveness and safety of replacement substance P to ameliorate or reverse cardiac fibrosis in type 2 diabetic monkeys. Four female T2DM African Green monkeys receive substance P (0.5 mgKgday S.Q. injection) for 8 weeks. We obtained cardiac magnetic resonance imaging and blood samples to assess left ventricular function and fibrosis by T1 map-derived extracellular volume as well as circulating procollagen type I C-terminal propeptide. Hematological parameters for toxicities were also assessed in these monkeys and compared with three female T2DM monkeys receiving saline S.Q. as a safety comparison group. Diabetic monkeys receiving replacement substance P exhibited a ∼20% decrease in extracellular volume (p 0.01), concomitant with ∼25% decrease procollagen type I C-terminal propeptide levels (p 0.008). Left ventricular ejection fraction was unchanged with substance P (p 0.42) however, circumferential strain was improved (p < 0.01). Complete blood counts, glycosylated hemoglobin A1c, lipids, liver and pancreatic enzymes, and inflammation markers were unchanged (p > 0.05). Replacement substance P reversed cardiac fibrosis in a large preclinical model of type 2 diabetes, independent of glycemic control. No hematological or organ-related toxicity was associated with replacement substance P. These results strongly support a potential application for replacement substance P as safe therapy for diabetic cardiac fibrosis.

Development and validation of a clinical score for identifying patients with high risk of latent autoimmune adult diabetes (LADA) The LADA primary care-protocol study.

Latent autoimmune diabetes in adults (LADA) is a type of diabetes mellitus showing overlapping characteristics between type 1 Diabetes Mellitus and type 2 Diabetes Mellitus (T2DM), and autoimmunity against insulin-producing pancreatic cells. For its diagnosis, at least one type of anti-pancreatic islet antibody (GADAb is the most common) is required. Many authors recommend performing this measure in all newly diagnosed patients with DM, but it is not possible in Primary Health Care (PHC) due to its high cost. Currently, a relevant proportion of patients diagnosed as T2DM could be LADA. Confusing LADA with T2DM has clinical and safety implications, given its different therapeutic approach. The main objective of the study is to develop and validate a clinical score for identifying adult patients with DM at high risk of LADA in PHC. This is an observational, descriptive, cross-sectional study carried out in Primary Care Health Centers with a centralized laboratory. All people over 30 years of age diagnosed with diabetes within a minimum of 6 months and a maximum of 4 years before the start of the study will be recruited. Individuals will be recruited by consecutive sampling. The study variables will be obtained through clinical interviews, physical examinations, and electronic medical records. The following variables will be recorded those related to Diabetes Mellitus, sociodemographic, anthropometric, lifestyle habits, laboratory parameters, presence of comorbidities, additional treatments, personal or family autoimmune disorders, self-perceived health status, Fourlanos criteria, and LADA diagnosis (as main variable) according to current criteria. The study will provide an effective method for identifying patients at increased risk of LADA and, therefore, candidates for antibody testing. However, a slight participation bias is to be expected. Differences between participants and non-participants will be studied to quantify this potential bias.

Interventions for depression and anxiety among people with diabetes mellitus Review of systematic reviews.

This review of systematic reviews of randomized clinical trials summarized the available evidence regarding the effectiveness and safety of interventions to treat depression andor anxiety in people with type 1 and type 2 diabetes. The sources of information searched were the Cochrane Library, MEDLINE, EMBASE, Web of Science and LILACS, until up to December 1st, 2022. The interventions were compared with placebo, active control or usual care. The measured primary outcomes were improvement in depression and anxiety remission, reduction of diabetes-specific emotional distress and improvement in quality of life. Two reviewers, independently, selected the reviews, extracted their data, and assessed their methodological quality using AMSTAR-2. A narrative synthesis of the findings was performed, according to the type of intervention and type of diabetes. Thirteen systematic reviews that included 28,307 participants were analyzed. The reviews had at least one critical methodological flaw. Cognitive Behavioral Therapy improved the mainly depression, glycemic values (n 5 reviews) and anxiety (n 1), in adults and elderly with diabetes. Collaborative care (n 2) and health education (n 1) improved depression and glycemic values, in adults with diabetes. Pharmacological treatment (n 2) improved depression outcomes only. The quality of the evidence was low to moderate, when reported. The interventions reported in literature and mainly the Cognitive Behavioral Therapy can be effective to treat people with diabetes and depression however, some findings must be confirmed. This study can guide patients, their caregivers and health professionals in making decisions concerning the use of these interventions in the mental healthcare of people with diabetes. Protocol Registration PROSPERO (CRD42021224587).

Interleukin-39 is a novel cytokine associated with type 2 diabetes mellitus and positively correlated with body mass index.

It is suggested that cytokines play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, this study explored two recently discovered cytokines, interleukin (IL)-37 (anti-inflammatory) and IL-39 (pro-inflammatory), in T2DM due to limited data in this context. Serum IL-37 and IL-39 levels were determined in 106 T2DM patients and 109 controls using enzyme-linked immunosorbent assay kits. Serum levels (median and interquartile range) of IL-37 (79 47-102 vs. 60 46-89 ngL probability p .04) and IL-39 (66 59-69 vs. 31 19-42 ngL p < .001) were significantly elevated in T2DM patients compared to controls. As indicated by the area under the curve (AUC), IL-39 (AUC 0.973 p < .001) was more predictable for T2DM than IL-37 (AUC 0.582 p .039). Elevated levels of IL-39 were significantly associated with T2DM (odds ratio 1.30 p < .001), while IL-37 did not show this association. Classification of IL-37 and IL-39 levels by demographic and clinical characteristics of patients revealed some significant differences including gender (IL-39), body mass index (BMI IL-37 and IL-39) and diabetic neuropathy (IL-39). BMI was positively correlated with IL-39 (correlation coefficient r IL-37 and IL-39 levels were elevated in the serum of T2DM patients. Besides, IL-39 is proposed to be a novel cytokine associated with T2DM and positively correlated with BMI.

Human pancreatic islet microRNAs implicated in diabetes and related traits by large-scale genetic analysis.

Genetic studies have identified ≥240 loci associated with the risk of type 2 diabetes (T2D), yet most of these loci lie in non-coding regions, masking the underlying molecular mechanisms. Recent studies investigating mRNA expression in human pancreatic islets have yielded important insights into the molecular drivers of normal islet function and T2D pathophysiology. However, similar studies investigating microRNA (miRNA) expression remain limited. Here, we present data from 63 individuals, the largest sequencing-based analysis of miRNA expression in human islets to date. We characterized the genetic regulation of miRNA expression by decomposing the expression of highly heritable miRNAs into

Prevalence of diabetes, epidemiological characteristics and vascular complications.

To estimate prevalence of diabetes in outpatient care and to describe its epidemiological characteristics, comorbidities, and related vascular complications. Observational cross-sectional study which included all adults affiliated from a private insurance health plan on March 2019, at Hospital Italiano de Buenos Aires, from Argentina. The global prevalence of diabetes resulted in 8.5% with 95% CI 8.3-8.6 (12,832 out of a total of 150,725 affiliates). The age stratum with the highest prevalence was the group between 65 and 80 years old with 15.7% (95% CI 15.3-16.1). People with diabetes had a mean age of 70 years (SD 14), 52% were women, and the most frequently associated cardiovascular risk factors were dyslipidaemia (88%), arterial hypertension (74%) and obesity (55%). In relation to metabolic control, 60% had at least one glycosylated hemoglobin measured in the last year, 70% of which were less than 7%. Almost 80% have LDL measured at least once in the last 2 years, 55% of them had an LDL value equal to or less than 100 mgdl. The macrovascular complications present in order of frequency were acute myocardial infarction (11%), cerebrovascular accident (8%) and peripheral vascular disease (4%) while the microvascular complications were found to be diabetic neuropathy (4%) and retinopathy (2%). 7% had diabetic foot, with less than 1% amputations. Diabetes represents a prevalent problem, even in elderly patients. This population continues to present a high cardiovascular risk, with little compliance with therapeutic goals. Estimar la prevalencia de diabetes en atención ambulatoria y describir sus características epidemiológicas, comorbilidades y complicaciones vasculares relacionadas. Corte transversal que incluyó la totalidad de adultos afiliados a la prepaga del Hospital Italiano de Buenos Aires en marzo de 2019, Argentina. La prevalencia global de diabetes resultó del 8.5% con intervalo de confianza del 95% (IC95%) 8.3-8.6 (12,832 de un total de 150,725 afiliados). El estrato etario con mayor prevalencia fue el grupo entre 65 y 80 años, con un 15.7% (IC95% 15.3-16.1). Las personas con diabetes presentaban una media de edad de 70 años (desviación estándar 14), el 52% eran mujeres, y los factores de riesgo cardiovasculares más frecuentemente asociados fueron dislipidemia (88%), hipertensión arterial (74%) y obesidad (55%). En relación con el control metabólico, el 60% tenía al menos una hemoglobina glucosilada medida en el último año, siendo el 70% de estas menores al 7%. Casi el 80% tiene medido el colesterol vinculado a lipoproteínas de baja densidad (c-LDL) al menos una vez en los últimos dos años, de ellos el 55% presentaba un valor de c-LDL igual o menor a 100 mgdl. Las complicaciones macrovasculares presentes en orden de frecuencia fueron infarto agudo de miocardio (11%), accidente cerebrovascular (8%) y enfermedad vascular periférica (4%) mientras que las complicaciones microvasculares resultaron ser neuropatía diabética (4%) y retinopatía (2%). El 7% tuvo pie diabético, con menos del 1% de amputaciones. La diabetes representa un problema prevalente, incluso en pacientes ancianos. Esta población sigue presentando un elevado riesgo cardiovascular, con escaso cumplimiento de objetivos terapéuticos.

Hyperuricemia Predicts the Progression of Type 2 Diabetic Kidney Disease in Chinese Patients.

Diabetic kidney disease (DKD) has a high global disease burden and substantially increases the risk of end-stage renal disease and cardiovascular events. High levels of serum uric acid (SUA), or hyperuricemia, may indicate patients with type 2 diabetes (T2D) at risk for kidney disease. This study explored the association between SUA levels and progression of kidney disease among patients with T2D. A cross-sectional study of 993 Chinese patients aged 20-75 years with T2D and DKD was conducted. Patients were stratified by progression risk of kidney disease based on estimated glomerular filtration rate and ratio of urinary albumin to creatinine, according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Ordinal logistic regression was used to assess associations between SUA and different KDIGO risk categories. Among 768 patients in the final analysis, those with hyperuricemia and higher SUA were more likely to be assigned to higher KDIGO risk categories. Patients with SUA > 420 μmolL were ninefold more likely to be in a higher KDIGO risk category than those with SUA < 300 μmolL (odds risk 9.74, 95% confidence interval 5.47-17.33, P < 0.001). Hyperuricemia may be associated with higher risk of DKD progression in individuals with T2D.

Plasma levels of GlycA, a pro-inflammatory glycoprotein biomarker, associate with an increased risk of microvascular complications in patients with type 2 diabetes (Zodiac-62).

GlycA, a pro-inflammatory glycoprotein biomarker, associates with newly developed type 2 diabetes (T2D). We determined the association of plasma GlycA with the development of microvascular complications in patients with established T2D. Plasma GlycA was measured by nuclear magnetic resonance spectrometry in T2D patients without microvascular complications at baseline (n 145) participating in a longitudinal cohort study of primary care-treated T2D patients (Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study). Associations of GlycA with incident microvascular complications including nephropathy, retinopathy, and neuropathy, were determined by Cox proportional hazards regression analyses. After a median follow-up of 3.2 (interquartile range IQR 2.9-3.4) years, 49 patients (33.8%) developed one or more microvascular complications. Median GlycA levels were 453.5 (IQR 402.0-512.8) μmoll. GlycA was associated with incident microvascular complications (hazard ratio HR per 1-SD increment 1.28 95% confidence interval CI1.00-1.63, P 0.048), even after adjustment for potential confounders and high-sensitive C-reactive protein (hs-CRP), HR 1.79 95%CI1.25-2.57, P 0.001). In contrast, hs-CRP levels were not significantly associated with the risk of developing microvascular complications (P 0.792). Higher plasma GlycA is associated with an increased risk of developing microvascular complications in T2D patients. Altered N-glycan branching associated with acute-phase reactive proteins may represent a preferred biomarker of systemic low-grade inflammation in predicting diabetic complications.

Intestinal cancer development in response to oral infection with high-fat diet-induced Type 2 diabetes (T2D) in collaborative cross mice under different host genetic background effects.

Type 2 diabetes (T2D) is a metabolic disease with an imbalance in blood glucose concentration. There are significant studies currently showing association between T2D and intestinal cancer developments. High-fat diet (HFD) plays part in the disease development of T2D, intestinal cancer and infectious diseases through many biological mechanisms, including but not limited to inflammation. Understanding the system genetics of the multimorbidity of these diseases will provide an important knowledge and platform for dissecting the complexity of these diseases. Furthermore, in this study we used some machine learning (ML) models to explore more aspects of diabetes mellitus. The ultimate aim of this project is to study the genetic factors, which underline T2D development, associated with intestinal cancer in response to a HFD consumption and oral coinfection, jointly or separately, on the same host genetic background. A cohort of 307 mice of eight different CC mouse lines in the four experimental groups was assessed. The mice were maintained on either HFD or chow diet (CHD) for 12-week period, while half of each dietary group was either coinfected with oral bacteria or uninfected. Host response to a glucose load and clearance was assessed using intraperitoneal glucose tolerance test (IPGTT) at two time points (weeks 6 and 12) during the experiment period and, subsequently, was translated to area under curve (AUC) values. At week 5 of the experiment, mice of group two and four were coinfected with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) strains, three times a week, while keeping the other uninfected mice as a control group. At week 12, mice were killed, small intestines and colon were extracted, and subsequently, the polyp counts were assessed as well, the intestine lengths and size were measured. Our results have shown that there is a significant variation in polyps number in different CC lines, with a spectrum between 2.5 and 12.8 total polyps on average. There was a significant correlation between area under curve (AUC) and intestine measurements, including polyp counts, length and size. In addition, our results have shown a significant sex effect on polyp development and glucose tolerance ability with males more susceptible to HFD than females by showing higher AUC in the glucose tolerance test. The ML results showed that classification with random forest could reach the highest accuracy when all the attributes were used. These results provide an excellent platform for proceeding toward understanding the nature of the genes involved in resistance and rate of development of intestinal cancer and T2D induced by HFD and oral coinfection. Once obtained, such data can be used to predict individual risk for developing these diseases and to establish the genetically based strategy for their prevention and treatment.

Implementation of self-monitoring of blood glucose for patients with insulin-dependent diabetes at a rural non-communicable disease clinic in Neno, Malawi.

Self-monitoring of blood glucose (SMBG) is a widely accepted standard of practice for management of insulin-dependentdiabetes, yet is largely unavailable in rural sub-Saharan Africa (SSA). This prospective cohort study is the first known report ofimplementation of SMBG in a rural, low-income country setting. To evaluate adherence and change in clinical outcomes with SMBG implementation at two rural hospitals in Neno, Malawi. Forty-eight patients with type 1 and insulin-dependent type 2 diabetes were trained to use glucometers and logbooks. Participantsmonitored preprandial glucose daily at rotating times and overnight glucose once a week. Healthcare providers were trained to evaluateglucose trends, and adjusted insulin regimens based on results. Adherence was measured as the frequency with which patients checked anddocumented blood glucose at prescribed times, while clinical changes were measured by change in glycated haemoglobin (HbA1c) over a6-month period. Participants brought their glucometers and logbooks to the clinic 95 - 100% of the time. Adherence with measuring glucose valuesand recording them in logbooks eight times a week was high (mean (standard deviation) 69.4% (15.7) and 69.0% (16.6), respectively). MeanHbA1c decreased from 9.0% (75 mmolmol) at enrolment to 7.8% (62 mmolmol) at 6 months (mean difference 1.2% (95% confidenceinterval (CI) 0.6 - 2.0 p0.0005). The difference was greater for type 1 diabetes (1.6% 95% CI 0.6 - 2.7 p0.0031) than for type 2 diabetes(0.9% 95% CI 0.1 - 1.9 p0.0630). There was no documented increase in hypoglycaemic events, and no hospitalisations or deaths occurred. SMBG is feasible for patients with insulin-dependent diabetes in a rural SSA population, and may be associated with improvedHbA1c levels. Despite common misconceptions, all patients, regardless of education level, can benefit from SMBG. Further research onlong-term retention of SMBG activities and the benefits of increasing frequency of monitoring is warranted.

Risk of dementia associated with body mass index, changes in body weight and waist circumference in older people with Type 2 Diabetes the Edinburgh Type 2 Diabetes Study.

To determine the relationship of dementia with preceding body mass index (BMI), changes in body weight and waist circumference in older people with type 2 diabetes METHODS In the Edinburgh Type 2 Diabetes Study (1064 men and women with type 2 diabetes, aged 60-75), body weight, waist circumference and BMI were measured at baseline and after 4 years in a sub-group (n821). Percentage body weight and waist circumference change over four years were calculated. Data on incident dementia was recorded during a median follow up time of 10.84 years. Survival models considering a range of co-variables andor death as a competing risk, were used to estimate the risks of dementia associated with each weight-related variable. A total of 105 incident dementia events were recorded. When compared with people in the lowest BMI group (<25 kgm Both a lower BMI and weight loss over a period of years are indicative of increased dementia risk for older people with type 2 diabetes, while waist circumference changes may be less informative.

Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus A 24-Week, Double-Blind, Randomized Trial.

Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mgday (n101) or dapagliflozin 10 mgday (n99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number NCT04634500). Adjusted mean change of HbA1c at week 24 was -0.80% with enavogliflozin and -0.75% with dapagliflozin (difference, -0.04% 95% confidence interval, -0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was -32.53 and -29.14 mgdL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (-1.85 vs. -1.31, P0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (-3.77 kg vs. -3.58 kg) and blood pressure (systolicdiastolic, -5.93-5.41 mm Hg vs. -6.57-4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Structure-based approach molecular insight of pyranocumarins against α-glucosidase through computational studies.

α-glucosidase is an enzyme that catalyzes the release of α-glucose molecules through hydrolysis reactions. Regulation of this enzyme can increase sugar levels in type-2 diabetes mellitus (DM) patients. Pyranocoumarin derivatives have been identified as α-glucosidase inhibitors. Through an

Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients survival.

We studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and T2D was diagnosed according to the ADA criteria. HT was classified according to the ACCAHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical andor molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. Two-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) ( Diabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies.

Immunologic, metabolic and genetic impact of diabetes on tuberculosis susceptibility.

Due to the increasing prevalence of diabetes mellitus (DM) globally, the interaction between DM and major global diseases like tuberculosis (TB) is of great public health significance, with evidence of DM having about a three-fold risk for TB disease. TB defense may be impacted by diabetes-related effects on immunity, metabolism, and gene transcription. An update on the epidemiological aspects of DM and TB, and the recent trends in understanding the DM-associated immunologic, metabolic, and genetic mechanisms of susceptibility to TB will be discussed in this review. This review highlights gaps in the incomplete understanding of the mechanisms that may relate to TB susceptibility in type 2 DM (T2DM). Understanding these three main domains regarding mechanisms of TB susceptibility in T2DM patients can help us build practical treatment plans to lessen the combined burden of the diseases in rampant areas.

Liraglutide Attenuates Hepatic Oxidative Stress, Inflammation, and Apoptosis in Streptozotocin-Induced Diabetic Mice by Modulating the Wnt

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus and also has hepatoprotective effects. However, the role of liraglutide treatment on liver injury in a mouse model of type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) and its underlying mechanisms remain to be elucidated. In the present study, diabetes was initiated in experimental animals by single-dose intraperitoneal inoculation of STZ. Forty female C57BL6J mice were equally assigned into five groups diabetic group, insulindiabetic group, liraglutidediabetic group, insulinliraglutidediabetic group, and control group for eight weeks. Diabetic mice exhibited a significantly elevated blood glucose level and decreased body weight, and morphological changes of increased steatosis and apoptosis were observed in the liver compared with the control. Furthermore, a significant increase in the levels of malondialdehyde and inflammatory markers such as tumor necrosis factor-

Nonsteroidal Mineralocorticoid Receptor Antagonist Eliciting Cardiorenal Protection Is a New Option for Patients with Chronic Kidney Disease.

Mineralocorticoid receptor antagonists (MRAs) protect cardiorenal function by robust anti-inflammatory and antifibrotic functions beyond classical functions of maintaining fluid and electrolyte homeostasis. The application of traditional steroidal MRAs to chronic kidney disease (CKD) has been limited by adverse events, especially when combined with renin-angiotensin system inhibitors, guideline-recommend drugs for CKD patients. Recently, the development of nonsteroidal MRAs gives patients with CKD a promising option. The discovery of nonsteroidal MRAs is based on the molecular structure of the mineralocorticoid receptor (MR) and differs in structure from spironolactone, a progesterone derivative. The structure of nonsteroidal MRAs determines their more effective and selective inhibition of MR providing patients more benefits with fewer adverse effects than MRAs. Recently, two types of nonsteroidal MRAs, finerenone and esaxerenone, have been authorized for clinical use. We elaborate on the physiological and pathophysiological mechanisms of MR, review the history of MRAs, compare two generations of MRAs, and introduce the forward clinical trials of finerenone and esaxerenone. Finerenone reduces the cardiovascular and kidney composite outcomes in diabetic patients with CKD eliciting a cardiorenal protection effect. Esaxerenone can effectively reduce blood pressure in hypertensive patients and albuminuria in diabetic patients with CKD. The risk of hyperkalemia is controllable and acceptable through the serum potassium-based dose titrate. Combination therapy with sodium-glucose cotransport-2 inhibition or a new potassium binder may be a safer and more efficient approach.

Financial, Occupational and Physical Challenges and Blood Glucose Monitoring in Type 2 Diabetes.

Blood glucose monitoring effects are changing for people living with type 2 diabetes. However, there is a lack of recent data surrounding financial, occupational, or physical stressors that affect the adherence of diabetes self-management practices. This article looks to examine specific financial, physical, and occupational challenges in adherence to blood glucose monitoring in type 2 diabetes. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 Pre-Pandemic data of adults 18 were analyzed. These data were used to examine the relationships between insurance coverage, health status, occupation, and self-monitoring of blood glucose levels in the United States. This study found that respondents had a statistically significant association with five variables prescription drug coverage (in-part or full), occupation status, gender, age, and three race subcategories (non-Hispanic White, Black, and Other-Multiracial) with blood glucose monitoring. This study may help certified health education specialists (CHES) and diabetes care and educator specialists (DCES) to better identify which groups of individuals are at highest risk for poor adherence to specific blood glucose monitoring in type 2 diabetes.

The effects of three different low-volume aerobic training protocols on cardiometabolic parameters of type 2 diabetes patients A randomized clinical trial.

To compare the effects of different aerobic training protocols on cardiometabolic variables in patients with type 2 diabetes mellitus (T2DM). This study was a parallel clinical trial. Fifty-two men and women with T2DM (>40 years) were randomly allocated into three groups, and 44 (22 males22 females) were included in the final analysis. Exercise intensity was based on the speed corresponding to the maximum oxygen consumption (v There was a significant difference between groups for changes on Low-volume HIIT promoted greater improvements in cardiorespiratory capacity in comparison with low-volume MICT, independent of the protocols used. There were no other differences between groups. All protocols improved at least one of the variables analyzed however, the most evident benefits were after the high-intensity protocols, especially L-HIIT.

Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes.

To evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes. Women (n96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks. The blood glucose levels, biochemical index, insulin resistance index (HOMA-IR), cost-effect ratio (CER), and drug safety were determined and compared between the two groups. Blood glucose levels, the biochemical index, and HOMA-IR were lower in both groups after the treatment ( Both Dulaglutide and Liraglutide can reduce blood glucose levels, improve biochemical index, and HOMA-IR levels in women with type 2 diabetes. Dulaglutide is more cost-effective and safe. httpswww.chictr.org.cnindex.aspx, identifier ChiCTR1900026514.

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 mlmin per 1.73 m The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAGCr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAGCr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Association of Triglyceride Glucose Index with Prevalence and Incidence of Diabetic Retinopathy in a Singaporean Population.

To examine the association of triglyceride glucose (TyG) index (product of fasting triglyceride and glucose) with prevalence and incidence of diabetic retinopathy (DR) in type 2 diabetes. 1339 patients from an ongoing Singapore Study of Macro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes (SMART2D) were included in this study. Fasting triglyceride and glucose levels were quantified and color fundus photographs were assessed for DR presence and severity. Logistic regression models were used to evaluate associations of TyG index with DR prevalence and incidence (median follow-up period 3.2 years). Mean TyG index was higher in patients with DR than no DR (9.24±0.7 versus 9.04± 0.6, p<0.001). TyG index was significantly associated with DR prevalence (OR1.4, CI 1.1-1.7, p0.002) and incidence (OR1.8, CI 1.04-2.9, p0.03), after adjusting for confounders. In a stratified analysis, the association between TyG index and DR prevalence reached significance only in the subgroup with HbA1c levels < 7.0% (OR2, CI 1.1-3.8, p0.03). TyG index significantly predicted DR prevalence and incidence with area under receiver operating curve as 0.77 (CI 0.74-0.80, p <0.001) and 0.66 (CI 0.57-0.76, p value <0.01), respectively. TyG index is a good predictor for DR prevalence and incidence. It can also be a secondary treatment target for patients with optimally controlled levels of HbA1c.

Uptake and effectiveness of online diabetes continuing education The perspectives of Thai general practitioner trainees.

Despite continuing medical education (CME) programmes on evidence-based diabetes care, evidence-based best practice and actual GP practice remain scant. Online CME offers numerous benefits to general practitioners (GPs), particularly during the coronavirus disease 2019 (COVID-19) pandemic. In Thailand, CME is a voluntary process and is yet to be established as a mandatory requirement. This study examined GP uptake of online diabetes CME and the changes in GPs attitudes to and knowledge of Type 2 diabetes management. A cross-sectional study and a before-and-after study were employed with 279 GP trainees who voluntarily undertook a newly-developed online diabetes programme. A follow-up survey was conducted six months after the GP trainees completed their training. One hundred and twelve out of 279 GP trainees (40.1%) participated in the study, of whom 37 (13.3%) enrolled in the online diabetes programme, and 20 (7.2%) completed the programme. Before enrolling in the programme, the participants mean diabetes knowledge score was 61.5%. The participants confidence in effective insulin treatment increased significantly after the programme (95% Confidence interval CI, -0.51-0.00 P 0.05), but their knowledge scores before and after the programme were not statistically different (95% CI, -3.93-0.59 P 0.14). Uptake of the online diabetes CME was poor, although appropriate recruitment strategies were employed, and the online educational option was attractive and accessible during the COVID-19 pandemic. This study emphasises the gap between evidence-based practice and actual GP practice and the need for mandatory CME.

Prediction of self-care behaviors among diabetic patients based on social cognitive theory.

Diabetes is a global health issue and the most prevalent chronic metabolic disease, which requires lifelong self-care behaviors. Thus, the present study was conducted with the aim of predicting the factors of self-care behaviors based on social cognitive theory in diabetic patients referred to comprehensive health service centers in Fasa. This cross-sectional research comprised 106 type 2 diabetes patients who were referred to Fasa service providers to determine the optimal solution. Outcomes were assessed using an existing demographic questionnaire, the diabetic self-care questionnaire, and a unique questionnaire to assess social cognitive theory, the validity and reliability of which were estimated. SPSS21 software with a Chi license was used for data analysis, and Spearman correlations, independent The age range of patients was between 33 and 67 years. There was a significant relationship between gender, education, and type of treatment with self-care. According to the findings, the variables of self-efficacy ( In designing and implementing educational interventions for self-care of diabetic patients, the theory of social cognition can be used as a framework to promote and maintain public health in patients.

Insights from yeast Transcriptional reprogramming following metformin treatment is similar to that of deferiprone in a yeast Friedreichs ataxia model.

In the absence of YFH1, the yeast ortholog of the human FXN gene, budding yeast Saccharomyces cerevisiae experience similar problems to those of cells with Friedreichs ataxia (FRDA). The comparable phenotypic traits consist of impaired respiration, problems in iron homeostasis, decreased oxidative stress tolerance, and diminished iron-sulfur cluster synthesis, rendering yeast of potential use in FRDA modeling and drug trials. Deferiprone, an iron chelator, is one of the long-term studied potential drugs for FRDA, whereas metformin is a biguanide prescribed to treat type 2 diabetes. In the present study, the effects of deferiprone and metformin treatment on the yeast FRDA model are explored via RNA-sequencing analyses. The comparative inquiry of transcriptome data reveals new promising roles for metformin in FRDA treatment since deferiprone and metformin treatments produce overlapping transcriptional and phenotypic responses in YFH1Δ cells. The results revealed that both deferiprone and metformin treatment does not rescue aerobic respiration in YFH1Δ cells, but they alleviate the FRDA phenotype probably by triggering the retrograde mitochondria-to-nucleus signaling.

Postprandial glucose-lowering effects by sago (

Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring.

The role of magnesium sulfate (MgSO

Rescue of High Glucose Impairment of Cultured Human Osteoblasts Using Cinacalcet and Parathyroid Hormone.

Patients with type 2 diabetes mellitus (T2DM) experience a higher risk of fractures despite paradoxically exhibiting normal to high bone mineral density (BMD). This has drawn into question the applicability to T2DM of conventional fracture reduction treatments that aim to retain BMD. In a primary human osteoblast culture system, high glucose levels (25 mM) impaired cell proliferation and matrix mineralization compared to physiological glucose levels (5 mM). Treatment with parathyroid hormone (PTH, 10 nM), a bone anabolic agent, and cinacalcet (CN, 1 µM), a calcimimetic able to target the Ca

Swedish Snuff (Snus), Cigarette Smoking, and Risk of Type 2 Diabetes.

Cigarette smoking is a known risk factor for Type 2 diabetes, but evidence regarding former smoking and moist snuff (snus) use and Type 2 diabetes risk is inconclusive. This study investigated the relationships of cigarette smoking and Swedish snus use with the risk of Type 2 diabetes in a cohort of middle-aged and elderly participants. Participants (N36,742 age range56-95 years) were followed for incident Type 2 diabetes and death between 2009 and 2017 through linkage to the Swedish National Patient, Prescribed Drug and Death Registers. Cox proportional hazards regression was used to obtain hazard ratios and 95% CIs adjusted for potential confounders, including physical activity, education, BMI, and alcohol intake. Analyses were conducted in 2021‒2022. Former and current smoking was associated with an increased risk of Type 2 diabetes (hazard ratios 95% CI1.17 1.07, 1.29 and 1.57 1.36, 1.81, respectively). In those who stopped smoking, Type 2 diabetes risk remained elevated up to approximately 15 years after cessation. In participants who have never smoked, snus use was linked to a higher risk of Type 2 diabetes in the model adjusted for age and sex (hazard ratio 95% CI1.49 1.04, 2.15), but this was attenuated after multivariable adjustment (hazard ratio 95% Cl1.29 0.89, 1.86). This study indicates that current and former smoking are associated with an increased risk of Type 2 diabetes in middle-aged and older individuals. There was less evidence of an association of snus use with the risk of Type 2 diabetes, suggesting that compounds other than nicotine may underlie the detrimental association of smoking with the risk of Type 2 diabetes.

The effectiveness of self-management programme based on multilevel social resources utilization in diabetes mellitus patients A randomized controlled study.

This study aimed to test the effects of a novel diabetes self-management education (DSME) programme focused on multilevel social resources utilization on improving self-management behaviour, social resources utilization and haemoglobin A A randomized controlled design was used. A total of 118 participants with T2DM from two communities were recruited through randomized sampling, and randomly assigned to the novel DSME group or the traditional DSME group. DSME focusing on multilevel social resources utilization was implemented in the novel DSME group. Data were collected at baseline (T Comparing these two groups, the participants in the novel DSME group reported significantly better improvement in self-management behaviour and social resources utilization at T The novel DSME programme focused on multilevel social resources utilization can effectively enhance T2DM patients self-management behaviour and social resource utilization and lower HbA

Remission with an Intervention Is Metabolic Surgery the Ultimate Solution

Long-term remission of type 2 diabetes following lifestyle intervention or pharmacotherapy, even in patients with mild disease, is rare. Long-term remission following metabolic surgery however, is common and occurs in 23% to 98% depending on disease severity and type of surgery. Remission after surgery is associated with excellent glycemic control without reliance on pharmacotherapy, improvements in quality of life, and major reductions in microvascular and macrovascular complications. For patients with type 2 diabetes, early intervention with metabolic surgery, when beta cell function still remains intact, provides the greatest probability of long-term remission as high as 90% or more.

Physiology Reconfigured How Does Bariatric Surgery Lead to Diabetes Remission

Bariatric surgery improves glucose homeostasis and glycemic control in patients with type 2 diabetes. Over the past 20 years, a breadth of studies has been conducted in humans and rodents aimed to identify the regulatory nodes responsible for surgical remission of type 2 diabetes. The review herein discusses central mechanisms of type 2 diabetes remission associated with weight loss and surgical modification of the gastrointestinal tract.

Intervention with Therapeutic Agents, Understanding the Path to Remission to Type 2 Diabetes Part 2.

Type 2 diabetes is characterized by progressive decline in pancreatic β-cell function. Newer agents, such as glucagon-like peptide-1 receptor agonist (GLP-1RA) and dual incretin agonists, can augment β-cell function and delay the need for additional antihyperglycemics. However, the effect on β-cell function ceases after stopping the medications. When combined with intensive lifestyle modifications, higher doses of GLP-1RA than those used for diabetes treatment can be used to induce weight loss. More research is needed on whether the weight loss achieved with GLP1-RA can be sustained after stopping medication and in turn can sustain diabetes remission.

Intervention with Therapeutic Agents, Understanding the Path to Remission in Type 2 Diabetes Part 1.

Type 2 diabetes is characterized by progressive decline in pancreatic β-cell function. Studies in adult subjects with newly diagnosed type 2 diabetes have reported that intensive insulin therapy followed by various antihyperglycemic medications can delay β-cell decline. However, this improvement is lost after cessation of therapy. In contrast, youth with type 2 diabetes experience a more rapid loss in β-cell function compared with adults and have loss of β-cell function despite being on insulin and other antihyperglycemic medications. In part one of this two-part review, we discuss studies aiming to achieve diabetes remission with insulin and oral antidiabetic medications.

Nonalcoholic Fatty Liver Disease.

Management of nonalcoholic fatty liver disease (NAFLD) is crucial for type 2 diabetes (T2D) remission because they are linked through the common pathophysiology of insulin resistance and lipotoxicity. One in three patients with T2D has nonalcoholic steatohepatitis leading to fibrosis, cirrhosis, and hepatocellular carcinoma. Noninvasive testing with imaging andor serum biomarkers can assess the risk for advanced liver disease. A liver biopsy is only necessary in select patients where there is diagnostic doubt. Treatments for NAFLD parallel T2D remission strategies focusing on weight loss and managing comorbid conditions through lifestyle modification, antiobesity medications, andor bariatric surgery, and T2D medications with proven efficacy.

Ameliorating Cardiovascular Risk in Patients with Type 2 Diabetes.

Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease (CVD), which constitutes the most common cause of morbidity and mortality in these patients. Intensive CVD risk factor control can ameliorate the elevated CVD associated with T2D. In this review, we provide an overview of CVD risk factor control, including traditional (blood pressure, glycemia, lipid, thrombosis, and lifestyle modifications) and nontraditional (social and environmental determinants of health) in patients with T2D, including evidence on management and outcomes.

Root Cause for Metabolic Syndrome and Type 2 Diabetes Can Lifestyle and Nutrition Be the Answer for Remission.

Obesity and its association with metabolic syndrome are implicated in many disease states. Research has focused on the role of diet and lifestyle modifications in the evolution of prediabetes to diabetes seeking ways to intervene and improve outcomes. Proven nutritional include leaner proteins, an abundance of vegetables, extra-virgin olive oil, and controlled portioning of carbs and starches. The transition from a sedentary state to an exercise routine of moderate intensity has shown efficacy in lowering metabolic risks. The synergy of dietary and physical activity modifications are the building blocks for lifestyle modifications examined in this review as a means of preventing obesity-related diabetes.

Association between integrase strand transfer inhibitor use with insulin resistance and incident diabetes mellitus in persons living with HIV a systematic review and meta-analysis.

Whether integrase strand transfer inhibitors (INSTIs) are associated with a higher risk of incident type 2 diabetes mellitus (DM) than other antiretroviral therapies (ART) needs to be established.MEDLINE, Embase, Web of Science, and ClinicalTrials.gov registries were searched for studies published between 1 January 2000 and 15 June 2022. Eligible studies reported incident DM or mean changes in insulin resistance measured by Homeostatic Model for Insulin Resistance (HOMA-IR) in patients on INSTIs compared with other ARTs. We performed random-effects meta-analyses to obtain pooled relative risks (RRs) with 95% CIs.A total of 16 studies were pooled 13 studies meta-analyzed for incident diabetes with a patient population of 72 404 and 3 for changes in HOMA-IR. INSTI therapy was associated with a lower risk of incident diabetes in 13 studies (RR 0.80, 95% CI 0.67 to 0.96, I

Stratification Of LIver Disease (SOLID) protocol for a prospective observational cohort study to determine the optimum biomarker strategies for the detection of advanced liver disease at the primary-secondary care interface.

Undiagnosed fatty liver disease is prevalent in the community, due to high rates of harmful alcohol consumption andor obesity. Fatty liver disease can progress to cirrhosis and its complications. Early identification of liver disease and treatment may prevent progression to cirrhosis. Biomarkers including FIB-4, enhanced liver fibrosis (ELF), PRO-C3 and vibration controlled transient elastography (VCTE) can stage liver fibrosis, but it is not known how well they perform in a primary care population. Moreover, no assessment of long-term prognostic ability of these biomarkers has been conducted in primary care. We aim to evaluate the performance of fibrosis biomarkers in primary care to develop a pathway to detect advanced fibrosis. This prospective, observational cohort study will recruit 3000 individuals with fatty liver disease risk factors (obesity, type 2 diabetes or hazardous alcohol consumption) at their primary care annual chronic disease review. Participants will have a liver health check. Two pathways will be evaluated (1) all have FIB-4, ELF and VCTE performed, and (2) patients have an initial assessment with FIB-4 and ELF, followed by VCTE in only those with increased FIB-4 andor ELF. Individuals with suspected significantadvanced liver fibrosis (liver stiffness measurement>8 kPa), will be reviewed in secondary care to confirm their fibrosis stage and institute treatment. The performance of FIB-4, ELF, PRO-C3, VCTE and novel biomarkers alone or in combination for advanced fibrosiscirrhosis will be evaluated. Participants will be followed longitudinally via their electronic health records to assess long-term clinical outcomes. Ethical approval was obtained from the London-Chelsea Research Ethics Committee (22PR0535 27 June 2022). Recruitment began on 31 October 2022. Outcomes of this study will be published in peer-reviewed journals and presented at scientific meetings. A lay summary of the results will be available for study participants and will be disseminated widely by LIVErNORTH.

Cardiovascular complications in insulin resistance and endocrine diseases.

Cerebrovascular diseases, such as stroke and cardiovascular disease, are one of the leading causes of death in Japan. Type 2 diabetes is the most common form of diabetes and an important risk factor for these diseases. Among various pathological conditions associated with type 2 diabetes, insulin resistance has already been reported to be an important risk factor for diabetic complications. The major sites of insulin action in glucose metabolism in the body include the liver, skeletal muscle, and adipose tissue. However, insulin signaling molecules are also constitutively expressed in vascular endothelial cells, vascular smooth muscle, and monocytesmacrophages. Forkhead box class O family member proteins (FoxOs) of transcription factors play important roles in regulating glucose and lipid metabolism, oxidative stress response and redox signaling, and cell cycle progression and apoptosis. FoxOs in vascular endothelial cells strongly promote arteriosclerosis by suppressing nitric oxide production, enhancing inflammatory response, and promoting cellular senescence. In addition, primary aldosteronism and Cushings syndrome are known to have adverse effects on the cardiovascular system, apart from hypertension, diabetes, and dyslipidemia. In the treatment of endocrine disorders, hormonal normalization by surgical treatment and receptor antagonists play an important role in preventing cardiovascular complications.

The association between type 2 diabetes and attention- deficithyperactivity disorder A systematic review, meta-analysis, and population-based sibling study.

We conducted a systematic review and a meta-analysis to quantitatively summarize evidence on the association between attention-deficithyperactivity disorder (ADHD) and type 2 diabetes (T2D). Moreover, a register-based sibling study was conducted to simultaneously control for confounding factors. A systematic search identified four eligible observational studies (N 5738,287). The meta-analysis showed that individuals with ADHD have a more than doubled risk of T2D when considering adjusted estimates (OR2.29 1.48-3.55, d0.46). Results from the register-based Swedish data showed a significant association between ADHD and T2D (HR2.35 2.14-2.58), with substance use disorder, depression, and anxiety being the main drivers of the association, and cardiovascular and familiar risk playing a smaller role. While results from the meta-analysis provide evidence for an increased risk of T2D in individuals with ADHD, the register-based analyses show that the association between ADHD and T2D is largely explained by psychiatric comorbidities. Pending further evidence of causal association, our findings suggest that early identification and treatment of ADHD comorbidities might greatly reduce the risk of developing T2D in individuals with ADHD.

Hypoglycemic effect of the dry leaf extract of Myrcia multiflora in streptozotocin-induced diabetic mice.

Myrcia multiflora (Lam) DC. is a medicinal plant used in folk medicine for diabetes control, mainly in the Brazilian Amazon. The leaves of this species has already demonstrated antidiabetic properties however, in mice with type 2 diabetes (DM2), the cumulative effect of the consumption of the dry extract of M. multiflora leaves (Mm) has not yet been reported. To investigate the effect of the dry extract obtained from the infusion of the dried leaves of M. multiflora on the blood glucose levels of diabetic mice. DM2 was induced in Swiss male mice by a single intraperitoneal injection of streptozotocin 150 mgkg body weight (bw). The animals were divided into two control groups (healthy and diabetic without treatment) and three sample groups that received Mm (25 and 50 mgkg bw) and acarbose (200 mgkg bw) by gavage once daily for 28 days (D28). Additionally, biochemical parameters, thiobarbituric acid reactive species (TBARS) levels in the liver, and histopathological analyses of the kidneys and liver were performed. On the seventh day of treatment, a 74.7% reduction in glucose levels were observed in the group of diabetic animals treated with Mm (50 mgkg bw) when compared to the beginning of the treatment. At D28, the hypoglycemic effect was maintained. The results of the biochemical and histopathological parameters and the TBARS levels suggest that this dry extract exerts nephro- and hepatoprotective effects. The findings demonstrate the potential that this extract has to inhibit the α-glucosidase enzyme, and it acts similarly to the positive control acarbose. Furthermore, this extract is nephro- and hepatoprotective. Therefore, this dry extract has the potential to be an adjuvant for DM2, which corroborates its use in folk medicine.

Acarbose diminishes postprandial suppression of bone resorption in patients with type 2 diabetes.

The alpha-glucosidase inhibitor acarbose is an antidiabetic drug delaying assimilation of carbohydrates and, thus, increasing the amount of carbohydrates in the distal parts of the intestines, which in turn increases circulating levels of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1). As GLP-1 may suppress bone resorption, acarbose has been proposed to potentiate meal-induced suppression of bone resorption. We investigated the effect of acarbose treatment on postprandial bone resorption in patients with type 2 diabetes and used the GLP-1 receptor antagonist exendin(9-39)NH In a randomised, placebo-controlled, double-blind, crossover study, 15 participants with metformin-treated type 2 diabetes (2 women13 men, age 71 (57-85 years), BMI 29.7 (23.6-34.6 kgm Compared to placebo, acarbose impaired the MMT-induced suppression of CTX as assessed by baseline-subtracted area under curve (P 0.0037) and nadir of CTX (P 0.0128). During acarbose treatment, exendin(9-39)NH In patients with type 2 diabetes, treatment with acarbose reduced postprandial suppression of bone resorption. Acarbose-induced GLP-1 secretion may contribute to this phenomenon as the impairment was partially reversed by GLP-1 receptor antagonism. Also, acarbose-induced reductions in other factors reducing bone resorption, e.g. glucose-dependent insulinotropic polypeptide, may contribute.

Indicators of Kidney Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease Treated With Dulaglutide.

In the AWARD-7 study in patients with type 2 diabetes and moderate-to-severe chronic kidney disease, once-weekly dulaglutide slowed the decline in estimated glomerular filtration rate (eGFR) and decreased the urine albumincreatinine ratio compared to insulin glargine at the end of 52 weeks of treatment. In this exploratory post hoc analysis, changes in two fibrosis biomarkers, serum PRO-C6 (type VI collagen formation) and urine C3M (type III collagen degradation) were evaluated. In the groups treated with dulaglutide 1.5 mg or insulin glargine (N330), serum PRO-C6 and urine C3M were measured using competitive enzyme-linked immunosorbent assays. Biomarker changes were assessed by a mixed-effects model for repeated measures. Pearson correlation analyses were conducted to determine associations between changes in kidney fibrosis biomarkers and eGFR measures at 52 weeks. At weeks 26 and 52 of treatment in the overall population, serum PRO-C6 levels were significantly lower in the dulaglutide group versus insulin glargine group with percent change from baseline of (least squares mean ± standard error) -4.6% ± 1.9 and -0.2% ± 2.2 versus 5.7% ± 2.0 and 8.0% ± 2.3 (p<0.01), respectively, and urine C3M levels were significantly higher in the dulaglutide group versus insulin glargine group with percent change from baseline of 10.9% ± 8.2 and 20.7% ± 8.8 versus -10.0% ± 6.5 and -16.9% ± 6.4 (p<0.05), respectively. These findings appeared greater in the subgroup with macroalbuminuria. Serum PRO-C6 negatively correlated with eGFR, while urine C3M positively correlated with eGFR. Dulaglutide treatment was associated with biomarker changes that indicated lower type VI collagen formation and higher type III collagen degradation compared to treatment with insulin glargine, suggesting a potential drug effect to reduce kidney fibrosis.

The postprandial actions of GLP-1 receptor agonists The missing link for cardiovascular and kidney protection in type 2 diabetes.

Recent clinical trials in people with type 2 diabetes have demonstrated beneficial actions on heart and kidney outcomes following treatment with GLP-1RAs. In part, these actions are consistent with improved glucose control and significant weight loss. But GLP-1RAs may also have additive benefits by improving postprandial dysmetabolism. In diabetes, dysregulated postprandial nutrient excursions trigger inflammation, oxidative stress, endothelial dysfunction, thrombogenicity, and endotoxemia alter hormone levels and modulate cardiac output and regional blood and lymphatic flow. In this perspective, we explore the actions of GLP-1RAs on the postprandial state and their potential role in end-organ benefits observed in recent trials.

Point of care ultrasound impact in acute heart failure hospitalization A retrospective cohort study.

Acute decompensated heart failure (ADHF) is one of the most frequent causes of emergency department (ED) visits. Point-of-Care Ultrasound (POCUS) is a reliable, easy-to-use, and available tool for an accurate diagnosis of ADHF. We aimed to analyze the impact of introducing POCUS as an additional tool to clinical standard diagnosis in clinical times of hospitalized heart failure patients. Retrospective cohort study comparing patients consulting to ED for heart failure acute decompensation previous to the rutinary use of POCUS versus patients who received an ultrasound-guided diagnosis at entrance. Ultrasound evaluation was additional to standard diagnosis (which included natriuretic peptides, images, etc). Cumulative incidence functions were calculated for time to treatment, time to disposition decision, and time to discharge. We used a flexible parametric model for estimate the time ratio (TR) in order to reflect the effect of POCUS. A total of 149 patients were included. The most frequent comorbid condition was hypertension (71.8%) followed by type 2 diabetes (36.2%). B type natriuretic peptide (BNP) was over 500 ngml. Most patients had Stevenson B profile (83.9%) at admission. In the cumulative incidence model (Fig. A), the TR (time ratio) for the outcome time to treatment was 1.539 (CI 95% 0.88 to 2.69). The TR for the outcome time to disposition decision was 0.665 (CI 95% 0.48 to 0.99). The TR for the outcome time to discharge (hospital length of stay) was 0.663 (CI 95% 0.49 to 0.90). In our study, the introduction of POCUS to ADHF patients decreases time to disposition decision and total length of hospital stay. Conversely, time to treatment augments. There is need for the evaluation of ultrasound as an intervention in clinical trials to confirm these findings.

Insulin receptor substrate-1 gene polymorphism and lipid panel data in type 2 diabetic patients with comorbid obesity andor essential hypertension.

Fatty acid correlations with HOMA-IR and HOMA-% β are differentially dictated by their serum free and total pools and flaxseed oil supplementation.

Cotadutide effect in liver and adipose tissue in obese mice.

Obesity, adipose tissue inflammation, and nonalcoholic fatty liver disease are associated with insulin resistance and type 2 diabetes. Cotadutide is a dual agonist GLP-1glucagon, currently in a preclinical study phase 2 that presents an anti-obesity effect. Diet-induced obese (DIO) C57BL6 mice were treated for four weeks with cotadutide (30 nmkg once a day at 2 pm). The study focused on epididymal white adipose tissue (eWAT), liver (nonalcoholic fatty liver disease, NAFLD), inflammation, lipid metabolism, AMPKmTOR pathways, and the endoplasmic reticulum (ER) stress. As a result, cotadutide controlled weight gain, glucose intolerance, and insulin resistance and showed beneficial effects on plasma markers in DIO mice (triacylglycerol, total cholesterol, alanine aminotransferase, and aspartate aminotransferase, leptin, adiponectin, monocyte chemoattractant protein-1, resistin, interleukin-6, tumor necrosis factor-alpha). Also, cotadutide lessened liver fat accumulation, eWAT proinflammatory markers, and ER stress. In addition, cotadutide improved lipid metabolism genes in eWAT, fatty acid synthase, peroxisome proliferator-activated receptor gamma, and mitigates adipocyte hypertrophy and apoptosis. Furthermore, the effects of cotadutide were related to liver AMPKmTOR pathway and ER stress. In conclusion, cotadutide induces weight loss and treats glucose intolerance and insulin resistance in DIO mice. In addition, cotadutide shows beneficial effects on liver lipid metabolism, mitigating steatosis, inflammation, and ER stress. Besides, in adipocytes, cotadutide decreases hypertrophy and reduces apoptosis. These actions rescuing the AMPK and mTOR pathway, improving lipid metabolism, and lessening NAFLD, inflammation, and ER stress in both eWAT and liver of DIO mice indicate cotadutide as a potentially new pharmacological treatment for T2D and associated obesity.

Fructose drives de novo lipogenesis affecting metabolic health.

Despite the existence of numerous studies supporting a pathological link between fructose consumption and the development of the metabolic syndrome and its sequelae, such as non-alcoholic fatty liver disease (NAFLD), this link remains a contentious issue. With this article, we shed a light on the impact of sugarfructose intake on hepatic de novo lipogenesis (DNL), an outcome parameter known to be dysregulated in subjects with type 2 diabetes andor NAFLD. In this review, we present findings from human intervention studies using physiological doses of sugar as well as mechanistic animal studies. There is evidence from both human and animal studies that fructose is a more potent inducer of hepatic lipogenesis than glucose. This is most likely due to the livers prominent physiological role in fructose metabolism, which may be disrupted under pathological conditions by increased hepatic expression of fructolytic and lipogenic enzymes. Increased DNL may not only contribute to ectopic fat deposition (i.e., in the liver), but it may also impair several metabolic processes through DNL-related fatty acids (e.g., beta-cell function, insulin secretion, or insulin sensitivity).

Perceived barriers and coping strategies developed by patients with type 2 diabetes mellitus to join to walking.

To investigate the perceived barriers and coping strategies for the practice of walking identified among patients with diabetes mellitus (DM) in the scope of the Unified Health System (SUS). A sample of 83 individuals with DM, SUS users, was asked to reflect on the obstacles that prevented them from walking, as well as to formulate coping plans to overcome them. The obstacles raised and plans developed were categorized for similarity and subjected to frequency analysis. The main obstacle reported was the feeling of dismay (36.1%). The most frequent coping plan to overcome the barriers found was social support from family members, neighbors and friends. The results made it possible to know the difficulties and potential of the subjects related to self-care for DM regarding the practice of walking, knowledge that can help the multidisciplinary teams of the SUS. Investigar as barreiras percebidas e as estratégias de enfrentamento para a efetivação da prática de caminhada identificadas entre portadores do diabetes mellitus (DM) no âmbito do Sistema Único de Saúde (SUS). Uma amostra de 83 portadores do DM, usuários do SUS, foi inquirida a refletir sobre os obstáculos que os impediam de praticar a caminhada, e formular planos de enfretamento para superar tais obstáculos. Foram categorizados os obstáculos levantados e os planos desenvolvidos quanto à similaridade e submetidos à análise de frequência. O principal obstáculo relatado foi o sentimento de desânimo (36,1%). O plano de enfrentamento mais frequente para superar as barreiras encontradas foi o apoio social de familiares, vizinhos e amigos. Os resultados possibilitaram conhecer as dificuldades e as potencialidades dos sujeitos relativas ao autocuidado para o DM no que se refere à prática da caminhada, conhecimento que pode auxiliar as equipes multidisciplinares do SUS. Investigar las barreras percibidas y las estrategias de afrontamiento para la práctica de la marcha identificadas en pacientes con diabetes mellitus (DM) en el ámbito del Sistema Único de Salud (SUS). Se solicitó les solicitó a 83 personas con DM, usuarias del SUS, que reflexionaran sobre los obstáculos que les impedían caminar, así como que formularan planes de afrontamiento para superarlos. Los obstáculos planteados y los planes desarrollados se clasificaron por similitud y se sometieron a análisis de frecuencia. El principal obstáculo reportado fue el sentimiento de consternación (36,1%). El plan de afrontamiento más frecuente para superar las barreras encontradas fue el apoyo social de familiares, vecinos y amigos. Los resultados permitieron conocer las dificultades y potencialidades de los sujetos relacionados con el autocuidado de la DM con respecto a la práctica de la marcha, conocimiento que puede ayudar a los equipos multidisciplinarios del SUS.

Management of medications and lifestyle to treat diabetes in the elderly.

To know the management practices of type 2 diabetes mellitus in the elderly regarding the use of medications and lifestyle. This is a qualitative and descriptive study, in which 20 elderly people with diabetes, residing in the interior of the State of Bahia, were interviewed between September 2016 and March 2017. The results were analyzed according to the Thematic Content Analysis proposed by Bardin. This project was approved by the Ethics Committee of the State University of Southwest Bahia under number 1.535.559. Two categories were identified after the analysis Managing diabetes medication and Managing lifestyle breaking, maintaining and adjusting behaviors. Management practices related to both the use of medications and the adopted lifestyle, as well as the experience coming from the own coexistence with the disease, have led to the reinterpretation of the scientific knowledge by professionals. It is also worth highlighting the dialogues and the cooperation received from the group studied, since they make possible enhancing and integrating this knowledge in daily actions to improve health status and promote comprehensive well-being. Healthcare professionals should implement person-centered care approaches and support users in making decisions about their health care. Conhecer as práticas de gerenciamento do diabetes mellitus tipo 2 entre pessoas idosas relacionadas ao uso de medicamentos e estilo de vida. Trata-se de pesquisa qualitativa e descritiva, em que foram entrevistadas 20 pessoas idosas com diabetes residentes no interior do estado da Bahia, Brasil, entre setembro de 2016 a março de 2017. Os resultados foram analisados pela Análise Temática proposta por Bardin, e o projeto foi aprovado pelo Comité de Ética em Pesquisa da Universidade Estadual do Sudoeste da Bahia, sob parecer n° 1.535.559. Emergiram duas categorias após a análise Gerenciando os remédios de diabetes e Gerenciando o estilo de vida entre rupturas, manutenções e ajustes. Nas práticas de gerenciamento relacionadas tanto ao uso dos medicamentos quanto ao estilo de vida adotado, houve reinterpretação do conhecimento científico orientado pelos profissionais, bem como o conhecimento oriundo da própria convivência com a doença. Cita-se, ainda, a colaboração dos diálogos com seu grupo de pertença, de modo que, integraram no cotidiano ações que concomitantemente ofereceram melhora da condição de saúde e promoveram o bem-estar enquanto pessoa em sua integralidade. Compete aos profissionais da equipe de saúde implementar abordagens de cuidado centrada na pessoa e apoiar os usuários na tomada de decisão sobre os cuidados com a sua saúde. Conocer las prácticas de gestión de la diabetes mellitus tipo 2 entre personas de edad avanzada, relacionadas con el uso de medicamentos y estilo de vida. Investigación cualitativa y descriptiva, en que fueron entrevistadas 20 personas de edad avanzada con diabetes, residentes en el interior del Estado de Bahía, Brasil, entre septiembre de 2016 y marzo de 2017. Los resultados fueron analizados por medio de la temática de Bardin. El proyecto fue aprobado por el comité de ética en investigación del Universidad Estatal del Suroeste de Bahía, con previo dictamen 1.535.559. Emergieron dos categorías por medio del análisis Administrando los medicamentos de diabetes y Administrando el estilo de vida entre rupturas, mantenimientos y ajustes. En las prácticas de gerenciamiento ha habido reinterpretación del conocimiento científico orientado por los profesionales, así como el conocimiento proveniente de la enfermedad propia. Cabe citar también la cooperación y los diálogos en el grupo, que potencian e integran acciones cotidianas de mejora de la condición de salud y promueven el bienestar integral de las personas. Los profesionales de la salud deben implantar estrategias de cuidado centradas en la persona y apoyar al usuario en la toma de decisiones sobre los cuidados de su salud.

Root canal microbiota as an augmented reservoir of antimicrobial resistance genes in type 2 diabetes mellitus patients.

Antimicrobial resistance is a global public health problem. Root canal microbiota associated with apical periodontitis represents a well-known reservoir of antimicrobial resistance genes (ARGs). However, the effect of type 2 diabetes mellitus (T2DM) in this reservoir is unknown. This study aimed to establish if root canal microbiota associated with apical periodontitis in T2DM patients is an augmented reservoir by identifying the prevalence of nine common ARGs and comparing it with the prevalence in nondiabetic patients. This cross-sectional study included two groups A T2DM group conformed of 20 patients with at least ten years of living with T2DM and a control group of 30 nondiabetic participants. Premolar or molar teeth with pulp necrosis and apical periodontitis were included. A sample was collected from each root canal before endodontic treatment. DNA was extracted, and ARGs were identified by polymerase chain reaction. tetW and tetM genes were the most frequent (93.3 and 91.6%, respectively), while ermA was the least frequent (8.3%) in the total population. The distribution of the ARGs was similar in both groups, but a significant difference (p<0.005) was present in ermB, ermC, cfxA, and tetQ genes, being more frequent in the T2DM group. A total of eighty percent of the T2DM patients presented a minimum of four ARGs, while 76.6% of the control group presented a maximum of three. Root canal microbiota associated with apical periodontitis in T2DM patients carries more ARGs. Therefore, this pathological niche could be considered an augmented reservoir.

Risk of type 2 diabetes mellitus in catholic priests compared with general public.

Although Catholic priests have a life of discipline with many responsibilities, there has been little research on the health effects of their lifestyle. Analysis of disease prevalence in priests will help elucidate the influence of religious life and occupational characteristics on the occurrence of diabetes. This retrospective study was performed to examine the differences in the prevalence of diabetes and prediabetes between Catholic priests and the general population. The study population comprised 1845 Catholic priests aged 31-80 years who visited the health promotion centers of three university hospitals in Korea between 2010 and 2019. Controls consisted of 1801 adult non-clerics aged 31-80 years who underwent health checkups at the screening center during the same period. Logistic regression analysis was performed to compare the differences in the rates of diabetes and prediabetes between the priest and control groups. Priests were younger and had lower rates of smoking, drinking alcohol, and hypertension compared with the control group. However, metabolic markers, such as BMI, waist circumference, body fat mass, insulin, HbA1c, and lipid profiles, were significantly higher in the priest group than the control group (all p < 0.05). After adjusting for covariates, the priest group had a significantly higher likelihood of having diabetes (OR 1.651, 95% CI 1.146-2.379) or prediabetes (OR 3.270, 95% CI 2.471-4.327) compared with the controls. This study showed that Catholic priests have higher risks of diabetes and prediabetes compared with the general population, and these risks increase with age. Further large-scale prospective studies are required to confirm these relationships.

Assessment of residual gastric volume using point-of-care ultrasonography in adult patients who underwent elective surgery.

Aspiration pneumonitis remains a dreaded complication that may lead to almost 9% of anaesthesia-related deaths. The presence of gastric contents has always been a contributing factor to an increased risk of aspiration. Preoperative gastric ultrasound has been suggested as a modality for determining residual volume in special populations and conditions. We conducted an observational study to determine the gastric residual volume in preoperative patients of elective surgery with gastric ultrasound and to study its correlation with patient factors. We enrolled 411 patients in the age group of 18-80 with ASA-PS I and II having BMI less than 35 kgm On qualitative assessment, 97 and 118 patients were observed to have distended stomachs in the supine and right lateral decubitus positions, respectively. On quantitative assessment, 336 had safe GRV, 60 patients were classified as having a low risk of aspiration (GRV < 1.5 mlkg) while 13 had a high risk of aspiration (> 1.5 mlkg). Eight patients with a fasting duration of more than ten hours and five who fasted between 6 and 10 h had a gastric residual volume of more than 1.5 mlh. Patients who were premedicated with histamine blockers had a statistically significant higher antral cross-sectional area (p-value - 0.022) and GRV (p-value - 0.018) in the right lateral decubitus position compared to patients who had taken proton pump inhibitors (PPIs). As BMI increased, there was a statistically significant (p-value < 0.001) increase in mean antral CSA in both supine and right lateral decubitus positions. There was a statistically significant association found between type 2 diabetes (p-value 0.045) with antral grade. Patients can have significant residual volume (> 1.5 mlkg) despite adequate fasting, and preoperative gastric ultrasound can help in assessing the same and guiding perioperative airway management. PPIs are more effective in reducing gastric residual volume as compared to histamine blockers. Patients with a BMI of more than 30 and type 2 diabetes mellitus have significant correlation with increased gastric residual volume mandating preoperative gastric ultrasound assessment for effective management. Patients with BMI over 30 and type 2 diabetes may benefit from POCGUS to guide perioperative airway management by stratifying GRV. Trial registration Name of registry-Clinical Trial Registry of India. Trial registration number-202003024083. Date of registration-19.3.2020. URL- httpctri.nic.inClinicaltrialspmaindet2.phptrialid39961EncHiduserName.

Altered glucose-dependent secretion of glucagon and ACTH is associated with insulin resistance, assessed by population analysis.

This study aimed to characterize how the dysregulation of counter-regulatory hormones contribute to diabetes by investigating the association between insulin sensitivity and the glucose- and insulin-dependent secretion of glucagon, ACTH and cortisol in non-diabetic individuals using a population model analysis. Data, from hyperinsulinemic-hypoglycemic clamps, were pooled for analysis, including 52 individuals with a wide range of insulin resistance (reflected by glucose infusion rate 20-60 min GIR20-60min). Glucagon secretion was suppressed by glucose and, to a lesser extent, insulin. The GIR20-60min and BMI were identified as predictors of the insulin effect on glucagon. At normoglycemia (5 mmolL), a 90% suppression of glucagon was achieved at insulin concentrations 16.3 μUmL and 43.4 μUmL in individuals belonging to the highest and lowest quantiles of insulin sensitivity, respectively. Insulin resistance of glucagon secretion explained the elevated fasting glucagon for individuals with a low GIR20-60min. ACTH secretion was suppressed by glucose and not affected by insulin. The GIR20-60min was superior to other measures as a predictor of glucose-dependent ACTH secretion, with 90% suppression of ACTH secretion by glucose at 3.1 and 3.5 mmolL for insulin-sensitive and insulin-resistant individuals, respectively. This difference may appear small but shifts the suppression range into normoglycemia for individuals with insulin resistance, thus, leading to earlier and greater ACTHcortisol response when glucose falls. Based on modeling of pooled glucose-clamp data, insulin resistance was associated with generally elevated glucagon and a potentiated cortisol-axis response to hypoglycemia, and over time both hormonal pathways may therefore contribute to dysglycemia and possibly type 2 diabetes.

Untargeted metabolomics reveals altered branch chain amino acids, glucose and fat metabolism contributing to coronary artery disease among Indian diabetic patients.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterised by increased blood glucose levels. Patients with T2DM have a high risk of developing atherosclerotic coronary artery disease (CAD). CAD with T2DM has a complex etiology and the understanding of the pathophysiology of coronary artery disease (CAD) in the presence of diabetes is poor. Here, we have used LC-MSMS-based untargeted metabolomics to unveil the alterations of metabolites in the serum of South-Indian patients diagnosed with T2DM, CAD and T2DM along with CAD (T2DM-CAD) compared with the healthy subjects (CT). Using untargeted metabolomics and network-based approaches, a set of metabolites highly co-expressed with T2DM-CAD pathogenesis were identified. Our results revealed that these metabolites belong to essential pathways such as amino acid metabolism, fatty acid metabolism and carbohydrate metabolism. The candidate metabolites identified by metabolomics study are branch chain amino acids, L-arginine, linoleic acid, L-serine, L-cysteine, fructose-6-phosphate, glycerol, creatine and 3-phosphoglyceric acid, and explain the pathogenesis of T2DM-assisted CAD. The identified metabolites could be used as potential prognostic markers to predict CAD in patients diagnosed with T2DM.

Impact of Intraoperative Hypothermia on Autologous Breast Reconstruction.

Studies have identified perioperative hypothermia as a risk factor for impaired wound healing, increased hospital length of stay, and surgical site infection. This study examines the effect of intraoperative hypothermia on postoperative outcomes in autologous microvascular free flap breast reconstruction. This was a retrospective review of 55 patients who experienced intraoperative hypothermia, defined as less than 35.0°C core body temperature and 99 normothermic patients who underwent autologous-based microvascular free flap breast reconstruction from 2013 to 2021. Demographics, comorbidities, smoking status, intraoperative warming devices, type of autologous reconstruction, hypothermia (and its duration), and length of surgery were collected. The outcomes assessed were infection rate, reoperation within 90 days, skin necrosis, wound healing complications, hematoma, seroma, and readmission within 90 days. In the study population of 154 consecutive patients, 8.4% had type 1 or type 2 diabetes and 3.2% were current smokers. A total of 90.3% of patients (139) underwent deep inferior epigastric perforator flap reconstruction, 7.1% (11) superficial inferior epigastric artery flap reconstruction, and 4 (2.6%) another free flap type. A total of 35.7% of the patients (55) experienced intraoperative hypothermia defined as less than 35.0°C. In the hypothermic group, a higher proportion of patients had wound healing complications (52.7% vs 29.3%, P < 0.05), hematoma (16.4% vs 5.1%, P < 0.05), and readmission for postoperative complications (34.5% vs 14.1%, P < 0.05). There was also a trend toward higher incidence of seroma (7.3% vs 5.1%), surgical site infection (12.7% vs 9.1%), skin necrosis (12.7% vs 9.1%), and unplanned reoperation within 90 days (10.9% vs 7.1%). Further analysis via Firth logistic regression demonstrated intraoperative hypothermia predicted postoperative hematoma (odds ratio OR, 3.68 95% confidence interval CI, 1.17-11.60 P < 0.05), readmission within 90 days (OR, 3.20 95% CI, 1.45-7.08 P < 0.05), and wound healing complications (OR, 2.69 95% CI, 1.36-5.33 P < 0.05). This study demonstrates that intraoperative hypothermia is a significant risk factor for postoperative wound healing complications, hematoma, and readmission within 90 days in autologous breast reconstruction. Because of a finite amount of donor sites, it is important to find ways to minimize the risk of postoperative complications. Our results support that maintaining strict normothermia during autologous breast reconstruction can significantly improve patient outcomes and reduce morbidity.

Preliminary Study of the Distinctive Mechanism of Shenqi Compound in Treating Rats with Type 2 Diabetes Mellitus by Comparing with Metformin.

In China, traditional Chinese medicine (TCM) has been used to treat type 2 diabetes mellitus (T2DM) for centuries. To investigate how the TCM ShenQi (SQC) formulation differs from metformin, four rat groups, including control, model, T2DM rats treated using SQC (SQC group), and T2DM rats treated using metformin (Met group), were constructed. The differentially expressed genes (DEGs) between SQC and metformin groups were screened, and the co-expression modules of the DEGs were constructed based on the weighted correlation network analysis (WGCNA) method. The correlation between modules and metabolic pathways was also calculated. The potential gene targets of SQC were obtained via the TCM systems pharmacology analysis. A total of 962 DEGs between SQC and Met groups were screened, and these DEGs were significantly enriched in various functions, such as sensory perception of the chemical stimulus, NADH dehydrogenase (ubiquinone) activity, and positive regulation of the fatty acid metabolic process. In addition, seven co-expression modules were constructed after the redundancy-reduced process. Four of these modules involved specific activated or inhibited metabolic pathways. Moreover, 334 effective ingredients of SQC herbs were collected, and four genes (RNASE1 (ribonuclease A family member 1, pancreatic), ADRB1 (adrenoceptor beta 1), PPIF (peptidylprolyl isomerase F), and ALDH1B1 (aldehyde dehydrogenase 1 family member B1)) were identified as potential targets of SQC. Comparing SQC with metformin to treat T2DM rats revealed several potential gene targets. These genes provide clues for elucidating the therapeutic mechanisms of SQC.

Obesity and kidney transplantation.

Obesity has reached epidemic proportions in the United States. It is a risk factor for developing, among others, heart disease, stroke, type 2 diabetes, and chronic kidney disease (CKD), and thus a major public health concern and driver of healthcare costs. Although the prevalence of obesity in the CKDend-stage kidney disease population is increasing, many obese patients are excluded from the benefit of kidney transplant based on their BMI alone. For this reason, we sought to review the experience thus far with kidney transplantation in obese patients and associated outcomes. Obesity is associated with a lower rate of referral and waitlisting, and lower likelihood of kidney transplantation. Despite increased risk for early surgical complications and delayed graft function, experience from multiple centers demonstrate a clear survival benefit of transplantation over dialysis in most obese patients, and comparable graft and patient survival rates to nonobese recipients. Data suggest that long-term transplant outcomes among obese recipients are similar to those among nonobese. Strategies to achieve pretransplant weight reduction and minimally invasive surgical techniques may further improve results of kidney transplantation in obese recipients.

Psychosocial factors predict medication adherence in young adults with youth-onset type 2 diabetes Longitudinal results from the TODAY2 iCount study.

To identify psychosocial predictors of medication adherence in young adults with youth-onset type 2 diabetes in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. Participants (mean age 26 years) completed validated psychosocial measures. Unannounced telephone pill counts were completed at T1 (baseline) and T2 (follow-up, approximately 1 year later) to assess adherence to oral hypoglycaemia agents (OHAs). Adherence to insulin was assessed by self-report. Logistic and linear regressions identified factors that predicted low adherence (<80% of pillsinsulin) and per cent adherence, adjusted for potential confounders. Of 171 participants with OHA adherence scores at T1 and T2 (65% women, 43% Hispanic and 35% non-Hispanic Black), 65.4% were low adherent. After adjustment (including T1 adherence), concerns about diabetes medicines (adverse effects, dependence) at T1 predicted higher odds of being low adherent (categorical) at T2 (p 0.019). Housing insecurity (p 0.045) and reporting ≥2 need insecurities (p 0.027) at T1 predicted lower per cent adherence (continuous) at T2. Of 157 participants with insulin adherence scores at T1 and T2 (69% women, 38% Hispanic and 38% non-Hispanic Black), 36.3% were low adherent. After adjustment (including T1 adherence), beliefs that medicines are overused predicted higher odds of insulin low adherence at T2 (p 0.013), and beliefs that medicines are harmful (p 0.004) and overused (p 0.010) predicted lower per cent insulin adherence at T2. Suboptimal medication adherence, common in young adults with youth-onset type 2 diabetes, is predicted by interfering beliefs about medicines and social factors. We must address these beliefs and unmet needs to develop tailored interventions for this vulnerable group.