Navigating the Predictive Landscape: DiaRem's Role in Unveiling Outcomes for Diabetes Remission following ESG.

PURPOSE: Rising obesity and type 2 diabetes mellitus (T2DM) rates can be mitigated by various strategies, with a 10% total body weight loss (TBWL) threshold often required for T2DM remission. T2DM remission rates after bariatric surgery like Roux-en-Y gastric bypass (RYGB) are well established; endoscopic sleeve gastroplasty (ESG) is a less invasive option that averages 15% TBWL and allows for T2DM remission. This study explores the DiaRem (Diabetes Remission post-RYGB) score's ability to predict T2DM remission 1-year post-ESG. MATERIALS AND METHODS: We conducted a retrospective cohort study on 39 individuals with T2DM who underwent ESG. Age, utilization of diabetes medications, insulin administration, and hemoglobin A1c levels were used to calculate the DiaRem score. The area under the receiver operating characteristic curve (AUC) was employed to evaluate the discriminative ability of DiaRem in distinguishing diabetes remission. RESULTS: Among the 39 patients with a median hemoglobin A1c of 6.7, 12.8% required insulin, and 43.6% used diabetes medication. At 1-year post-ESG, 69.2% of patients experienced diabetes remission with a median %TWBL of 12.7. The DiaRem score's ability to detect diabetes resolution for ESG patients had a sensitivity of 100% and a specificity of 58.3%, at the optimal cutoff value of 10. The AUC was 0.779 (95% CI 0.546-0.959). CONCLUSION: Our study demonstrated the DiaRem score's predictive value for T2DM remission post-ESG, highlighting its utility in clinical decision-making for ESG-related outcomes. Further investigation is needed to identify alternative indicators that may enhance predictive accuracy, thus refining personalized decision-making for this patient group.

Diabetes Self-Efficacy on Glycemic Control and Well-Being of Patients With Type 2 Diabetes Mellitus: An Analytical Cross-Sectional Study.

INTRODUCTION: Diabetes mellitus is a major, chronic, and progressive lifestyle disease. It adversely affects patients' quality of life, effectiveness, and well-being. Self-care practices are universally recognized as imperative to keep the illness under control and prevent complications. Self-efficacy is one of the factors involved in the successful self-care of diabetic patients. The primary objective of the study was to estimate the proportion of diabetes self-efficacy and to assess the correlation of diabetes self-efficacy with glycemic control, and the well-being of patients with type 2 diabetes mellitus (T2DM). The secondary objective was to assess the factors associated with diabetes self-efficacy. METHODS: An analytical cross-sectional study was conducted among T2DM patients attending the non-communicable disease clinic in the outreach centers of Government Medical College, Thiruvananthapuram, Kerala, India. Four hundred patients with T2DM were included in the study. Diabetes self-efficacy was assessed by the Stanford Diabetes Self-Efficacy Scale and the WHO-5 index scale was used to assess wellbeing. Glycemic control was determined by HbA1C estimation, with ≤7% as good control. RESULTS: Among 400 patients with T2DM, 51.25 % (95% CI: 46.2-56.2) had high diabetes self-efficacy. A significantly negative correlation was found between HbA1C and self-efficacy (r =- 0.208, p = 0.01), and a positive correlation was shown between well-being and self-efficacy (r = 0.418, p = 0.01). Logistic regression analysis found that factors associated with diabetes self-efficacy were upper socioeconomic status (OR = 8.53, 95% CI: 3.06-13.82), family support (OR = 1.97, 95% CI: 1.10-3.54), participation in diabetes education classes (OR = 1.95, 95% CI: 1.10-3.54), diet compliance (OR = 4.74, 95% CI: 2.80-8.01), glycemic control (OR = 1.69, 95% CI: 1.01-2.84), and overall wellbeing (OR = 6.7, 95% CI: 3.84-11.64). CONCLUSION: The proportion of high diabetes self-efficacy was 51.25% (95% CI: 46.2-56.2). The factors associated with diabetes self-efficacy were family support, participation in diabetes education classes, high socioeconomic status, absence of complications, good glycemic control, and well-being. The study findings depicted that high self-efficacy was significantly correlated with good glycemic control and well-being of patients with T2DM.

Metabolic factors are not the direct mediators of the association between type 2 diabetes and osteoporosis.

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role. Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship. Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship. Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.

Evaluation of Sleep Quality Among People Living With Type 2 Diabetes Mellitus in Taif, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND:  Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels, which are highly associated with poor sleep quality, cardiovascular disease, and pathological changes. This research examines the relationship between sleep quality and T2DM and compares it with nondiabetics within the Taif community. The findings of this study will provide valuable insights and recommendations to enhance the overall health quality in Taif, Saudi Arabia. METHODOLOGY:  A cross-sectional study was conducted on 547 patients with T2DM between December 1, 2023, and April 1, 2024, in Taif. The sleep quality was assessed using the Sleep Quality Questionnaire (SQQ). Data were collected using an online questionnaire with two parts: primary demographic data and an assessment of sleep quality using the SQQ. RESULTS:  Our study enrolled 814 participants, including 547 with T2DM and 267 nondiabetics. Participants with T2DM had poorer sleep quality, with a median score of 21 vs. 25 (P < 0.001). Significant factors affecting sleep quality included gender (P = 0.002), marital status (P = 0.023), and job status (P = 0.023). Nondiabetics had better sleep quality (76%) than participants with T2DM (61.1%). Males, married, and employed individuals reported higher sleep quality scores. CONCLUSIONS:  Research indicates that individuals with T2DM experience lower sleep quality than the general population, particularly among female, unmarried, and unemployed individuals. To enhance sleep quality in patients with T2DM, it is essential to increase awareness, provide education on proper sleep habits, and highlight the importance of effective diabetes management, screening for sleep disorders, and consistent monitoring.

Potential Benefits of Continuous Glucose Monitoring for Predicting Vascular Outcomes in Type 2 Diabetes: A Rapid Review of Primary Research.

(1) Background: Chronic hyperglycaemia is a cause of vascular damage and other adverse clinical outcomes in type 2 diabetes mellitus (T2DM). Emerging evidence suggests a significant and independent role for glycaemic variability (GV) in contributing to those outcomes. Continuous glucose monitoring (CGM) provides valuable insights into GV. Unlike in type 1 diabetes mellitus, the use of CGM-derived GV indices has not been widely adopted in the management of T2DM due to the limited evidence of their effectiveness in predicting clinical outcomes. This study aimed to explore the associations between GV metrics and short- or long-term vascular and clinical complications in T2DM. (2) Methods: A rapid literature review was conducted using the Cochrane Library, MEDLINE, and Scopus databases to seek high-level evidence. Lower-quality studies such as cross-sectional studies were excluded, but their content was reviewed. (3) Results: Six studies (five prospective cohort studies and one clinical trial) reported associations between GV indices (coefficient of variation (CV), standard deviation (SD), Mean Amplitude of Glycaemic Excursions (MAGE), Time in Range (TIR), Time Above Range (TAR), and Time Below Range (TBR)), and clinical complications. However, since most evidence came from moderate to low-quality studies, the results should be interpreted with caution. (4) Conclusions: Limited but significant evidence suggests that GV indices may predict clinical compilations in T2DM both in the short term and long term. There is a need for longitudinal studies in larger and more diverse populations, longer follow-ups, and the use of numerous CGM-derived GV indices while collecting information about all microvascular and macrovascular complications.

Serum ferritin level and associated factors among uncontrolled adult type II diabetic follow-up patients: comparative based cross-sectional study.

BACKGROUND: Uncontrolled type 2 diabetes mellitus (UT2DM) and its associated consequences nowadays have been a global health crisis, especially for adults. Iron has the property to oxidize and reduce reversibly, which is necessary for metabolic processes and excess accumulation of iron indicated by serum ferritin levels could have a significant impact on the pathophysiology of T2DM via generation of reactive oxygen species (ROS). However, no conclusive evidence existed about the association of serum ferritin with the state of glycemic control status. Therefore, this study aimed to evaluate serum ferritin levels and associated factors in uncontrolled T2DM patients and compare them with those of controlled T2DM and non-diabetic control groups. METHODS: A hospital-based comparative cross-sectional study was conducted among conveniently selected 156 study participants, who were categorized into three equal groups of uncontrolled T2DM, controlled T2DM, and non-diabetic control groups from October 2 to December 29, 2023 at St. Paul's Hospital Millennium Medical College. A pre-tested structured questionnaire was used to collect socio-demographic and diabetes-related information. The laboratory tests were done using an automated chemistry analyzer and IBM-SPSS statistical software (version-27) was utilized for data entry and analysis with a significance level of p < 0.05. RESULT: The mean serum ferritin level was noticeably higher in uncontrolled T2DM patients as compared to controlled T2DM and control groups (p < 0.001). It was significantly correlated with HbA1c [r = 0.457, p < 0.001], fasting blood sugar (FBs) [r = 0.386, p < 0.001], serum iron [r = 0.430, p < 0.001], and systolic blood pressure (SBP) [r = 0.195, p = 0.047] in T2DM patients. A multivariate logistic regression model revealed that a rise in HbA1c (AOR = 3.67, 95% CI(1.50-8.98), serum iron (AOR = 1.02, 95% CI(1.01-1.04), male gender (AOR = 0.16, 95% CI(0.05-0.57) and being on oral hypoglycemic agent (OHA) monotherapy (AOR = 0.26, 95% CI(0.07-0.95) were key associated factors for the elevated serum ferritin among T2DM patients. CONCLUSION: The present study demonstrated that T2DM patients had elevated serum ferritin levels which might be related to the existence of long-term hyperglycaemia and that serum ferritin had a significant positive association with HbA1c and FBs, implying that it could be used as an additional biomarker to predict uncontrolled T2DM patients.

An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies.

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.

Probiotics intervention for type 2 diabetes mellitus therapy: a review from proposed mechanisms to future prospects.

Type 2 diabetes mellitus (T2DM) is one of the metabolic diseases with the highest morbidity rates in the world. Probiotics have positive health impacts on human health and a considerable amount of research has demonstrated their beneficial effects in treating T2DM. However, probiotic intervention in T2DM has complex mechanisms because the pathogenesis of T2DM is complex. This review summarized the mechanisms of probiotic intervention in diabetes from the perspective of diabetes pathogenesis. First, the objectives of probiotic intervention in diabetes aimed at the intestinal tract reparative effects, pancreatic function, host metabolism and self-recovery were comprehensively reviewed. Next, we concluded the clinical application status of ingested probiotics in patients with T2DM, and an obvious imbalance exists between theoretical probiotic research and clinical applications. Finally, we summarized the emerging research on probiotic interventions in T2DM and analyzed the literature in this regard, including next-generation probiotics; suggestions for probiotics consumption with the aim of diabetic complications; as well as the association between novel mechanisms of diabetes remission with the potential for probiotic intervention. In conclusion, this review sheds light on the potential role of probiotics, from proposed mechanisms to prospects in relieving T2DM.

Involvement of interleukin-1ß in high glucose-activated proliferation of cholangiocarcinoma.

Background: Diabetes mellitus (DM) is associated with the increased risk of development and the advancement of cholangiocarcinoma (CCA). High glucose levels were previously shown for upregulating interleukin-1ß (IL-1ß) in CCA cells with unclear functions. The present study, thus, aimed to investigate molecular mechanisms linking DM to CCA progression, with IL-1ß hypothesized as a communicating cytokine. Methods: CCA cells were cultured in media with normal (5.6 mM) or high (25 mM) glucose, resembling euglycemia and hyperglycemia, respectively. Expressions of IL-1ß and IL-1 receptor (IL-1R) in CCA tissues from patients with and without DM were examined using immunohistochemistry. Functional analyses of IL-1ß were performed using siRNA and recombinant human IL-1R antagonist (rhIL-1RA), in which Western blots investigated the knockdown efficacy. BALB/c Rag-2-/- Jak3-/- (BRJ) mice were implanted with CCA xenografts to investigate hyperglycemia's effects on CCA growth and the anti-tumor effects of IL-1RA. Results: CCA tumors from patients with hyperglycemia showed significantly higher IL-1ß expression than those from non-DM patients, while IL-1ß was positively correlated with fasting blood glucose (FBG) levels. CCA cells cultured in high glucose showed increased IL-1ß expression, resulting in increased proliferation rates. Suppressing IL-1ß signaling by si-IL-1ß or rhIL-1RA significantly reduced CCA cell proliferation in vitro. Anakinra, a synthetic IL-1RA, also exerted significant anti-tumor effects in vivo and significantly reversed the effects of hyperglycemia-induced growth in CCA xenografts. Conclusions: IL-1ß plays a crucial role in CCA progression in a high-glucose environment. Targeting IL-1ß might, then, help improve therapeutic outcomes of CCA in patients with DM and hyperglycemia.

Exploring maternal and neonatal outcomes in women with Type-1 Diabetes: A study from Pakistan.

Background & Objective: Pregnancy in women diagnosed with Type-1 diabetes mellitus poses a higher risk of experiencing complications related to the health of the fetus, the mother, and the newborn, along with potential obstetric issues. The objective of this study was to examine the maternal and fetal outcomes, as well as complications faced by pregnant women with type-1 diabetes, and to identify potential preventable factors. Methods: This retrospective cohort study, conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University, Karachi, Pakistan (January 2022 - January 2023), focused on registered pregnancies of women with Type-1 diabetes. A predesigned questionnaire recorded demographic information, diabetes and obstetric history, clinical details, treatment specifics, maternal, perinatal, and neonatal outcomes. Results: This study included 100 women with pre-existing Type-1 diabetes (mean age: 15.11 ± 5.64 years at diabetes diagnosis). Of these, 72% reported unplanned pregnancies, with a mean HbA1C at conception 8.29%. Median gestational age at delivery was 32.15 ± 10.82 weeks. Delivery outcomes included 40% normal vaginal deliveries and 60% C-sections (9% emergency, 51% elective). Stillbirths occurred in 14 cases, while 16 women experienced one miscarriage, seven had two, and 10 had three miscarriages. Glycemic targets (fasting) were achieved in 55 women, and post-meal targets only in 29, whereas, neonatal complications included hypoglycemia in 13 and low birth weight in 12 neonates. Conclusion: The high frequency of unplanned pregnancies and cesarean sections along with poor management of pre-pregnancy care and poor glycemic control results in compromised maternal and perinatal outcomes in this high-risk group.

A sensitive, expandable AQC-based LC-MS/MS method to measure amino metabolites and sphingolipids in cell and serum samples.

Sphingolipids are a major lipid species found in all eukaryotes. Among structurally complex and diversified lipids, sphingoid bases have been heavily linked to various metabolic diseases. However, most current LC-MS-based methods lack the sensitivity to detect low-abundant sphingoid bases. The 6-Aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization reagent, which efficiently forms covalent bonds with amino groups, has been widely used for amino acid detection. Nevertheless, the commonly used reverse-phase HPLC method for amino acid analysis is not suitable for amphipathic sphingolipids. To address this issue, we report a robust reverse-phase HPLC-MS/MS method capable of separating and detecting hydrophilic amino acids and sphingoid bases in a single run with high sensitivity. This method is also inclusive of other amino metabolites with an expandable target list. We tested this method under various conditions and samples, demonstrating its high reproducibility and sensitivity. Using this approach, we systematically analyzed human serum samples from healthy individuals, dyslipidemia, and type II diabetes mellitus (T2DM) patients, respectively. Two sphingolipids and five amino acids were identified with significant differences between the control and T2DM groups, highlighting the potential of this method in clinical studies.

Influence of Dapagliflozin Dosing on Low-Density Lipoprotein Cholesterol in Type 2 Diabetes Mellitus: A Systematic Literature Review and Meta-Analysis.

A systematic literature review and meta-analysis was performed to evaluate the effects of dapagliflozin on low-density lipoprotein (LDL) cholesterol in type 2 diabetes mellitus. Data on changes in LDL cholesterol, adverse cardiac events (ACEs), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were pooled in a meta-analysis. Data from dose comparison trials were separately pooled, and meta-analysis was conducted by using RevMan (5.4.1) and R (4.1.2). Dapagliflozin increased LDL cholesterol by 2.33 mg/dL (95% CI, 1.46 to 3.19; I2 = 0%; P < .00001), increased risk of ACEs by 1.56 (95% CI, 1.02 to 2.39; I2 = 0%; P < .04), decreased HbA1c by -0.41% (95% CI, -0.44 to -0.39; I2 = 85%; P < .00001), and decreased FBG by -13.51 mg/dL (95% CI, -14.43 to -12.59; I2 = 92%; P < .00001) versus any placebo or active comparator. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 1.71 mg/dL (95% CI, -1.20 to 4.62; I2 = 53%; P = .25) versus a 5 mg dose and by 1.04 mg/dL (95% CI, -1.17 to 3.26; I2 = 62%; P = .36) versus a 2.5 mg dose. Dapagliflozin 10 mg monotherapy increased LDL cholesterol by 3.13 mg/dL (95% CI, 1.31 to 4.95; I2 = 0%; P = .0008), increased the risk of ACEs by 1.26 (95% CI, 0.56 to 2.87; I2 = 0%; P = .58), decreased HbA1c by -0.4% (95% CI, -0.45 to -0.35; I2 = 89%; P < .00001), and decreased FBG by -8.39 mg/dL (95% CI, -10 to -6.77; I2 = 96%; P < .00001) versus a placebo or active comparator. Dapagliflozin monotherapy resulted in a minimal but statistically significantly (P = .0002) increase in LDL cholesterol. However, this minor change does not increase the risk of ACEs (P = .17) when compared with placebo or active comparator.

A Case Report on Trastuzumab Emtansine (T-DM1) in a Patient With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer and Brain Metastases: Long-Term Treatment and Survival.

Breast cancer remains the most common cancer in women worldwide. Among women with breast cancer, brain metastases are very prevalent among HER2-positive and affect those in the advanced stages of the disease. Various factors, including molecular subtypes, performance status, extracranial disease status, leptomeningeal metastasis, and the number of lesions, significantly influence the prognosis of patients with brain metastases from breast cancer (BCBrM). Understanding and addressing the specific risks associated with different breast cancer subtypes is crucial for developing tailored and effective medical treatments. This report presents a case of a breast cancer patient with recurrent disease and brain metastases who achieved long-term survival following a treatment regimen that included radiotherapy and a T-DM1 biosimilar.

Diabetes mellitus service preparedness and availability: a systematic review and meta-analysis.

Background: In areas with limited resources, the lack of preparedness and limited availability of diabetes mellitus services in healthcare facilities contribute to high rates of illness and death related to diabetes mellitus. As a result, this study focused on analyzing the combined prevalence of preparedness and availability of diabetic services in countries with limited resources. Methods: A comprehensive search was conducted across various databases, such as PubMed/MEDLINE, Web of Science, Google Scholar, and African Journal Online. The search aimed to identify primary research articles that assessed the availability and preparedness of services for individuals with type 2 diabetes mellitus specifically. The articles included in the search spanned from January 2000 to 23 February 2024. To analyze the data, a meta-analysis of proportions was performed using the random-effects model. Additionally, the researchers assessed publication bias by examining a funnel plot and conducting Egger's test. Heterogeneity and sensitivity analyses were also conducted to evaluate the data. The findings of the study regarding the pooled prevalence of diabetes service preparedness and availability, along with their corresponding 95% confidence intervals, were presented using a forest plot. Results: A comprehensive analysis was conducted on 16 research articles that focused on service preparedness and 11 articles that examined service availability. The sample sizes for these studies were 3,422 for service preparedness and 1,062 for service availability. The findings showed that the pooled prevalence of diabetes service preparedness was 53.0% (95% CI: 47.0-60.0). Furthermore, in this systematic synthesis, the overall pooled prevalence of service availability for diabetes mellitus was 48% (95% CI: 36.0-67.0), with the highest pooled prevalence observed in Asia, with a pooled prevalence of 58% (95% CI: 38.0-89.0). Conclusion: Our study reveals a significant disparity in the preparedness and availability of services for diabetes mellitus, which falls below the minimum threshold set by the WHO. These findings should capture the attention of policymakers and potentially serve as a foundation for reevaluating the current approach to diabetes service preparedness and availability. To enhance the availability and preparedness of diabetes services, a tailored, multifaceted, and action-oriented approach to strengthening the health system is required. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024554911.

Risk factors for distant metastasis and prognosis of the penile cancer with distant metastasis.

Background: Penile cancer (PC) is a rare malignant tumor, whose distant metastasis (DM) is associated with the poorest outcomes. The risk factors associated with DM and prognosis of the PC with DM remain elusive. This study was aimed at investigating risk factors associated with DM and constructing prediction models of PC with DM. Methods: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database over a period of 2000-2020, including clinical characteristics such as age, marital status, tumor size, Tumor Node Metastasis (TNM) staging, and treatment information. Utilizing univariate and multivariate logistic regression, alongside cox regression analysis, we identified independent risk factors for DM and prognosis in the total cases and the cases with DM. Nomograms were developed for predicting DM and prognosis in PC patients. Results: Enrolling 1,488 cases, our study identified tumor size and N stage as independent predictors of DM. The predictive nomogram for DM achieved an area under the curve (AUC) of 0.904. Notably, the 1-, 3-, and 5-year cumulative survival rates for PC with DM were 35%, 17%, and 13%, respectively, with larger tumor size associated with prognosis of PC cases with DM. This study verified a correlation between advanced age and TNM stage, as well as chemotherapy with the poor PC prognosis. The nomogram yielded 0.72, 0.69 and 0.69, in predicting 1-, 3-, and 5-year overall survivals (OS), while 0.73, 0.70 and 0.69 in predicting 1-, 3-, 5-year cancer specific survivals (CSS), respectively. Conclusions: This study investigated risk factors of PC with DM. Also, nomograms for predicting DM, OS and CSS of PC patients were developed.

A consensus statement from the Japan Diabetes Society (JDS): a proposed algorithm for pharmacotherapy in people with type 2 diabetes-2nd Edition (English version).

The Japan Diabetes Society (JDS) adopted a sweeping decision to release consensus statements on relevant issues in diabetes management that require updating from time to time and launched a "JDS Committee on Consensus Statement Development." In March 2020, the committee's first consensus statement on "Medical Nutrition Therapy and Dietary Counseling for People with Diabetes" was published. In September 2022, a second consensus "algorithm for pharmacotherapy in people with type 2 diabetes" was proposed. In developing an algorithm for diabetes pharmacotherapy in people with type 2 diabetes, the working concept was that priority should be given to selecting such medications as would appropriately address the diabetes pathology in each patient while simultaneously weighing the available evidence for these medications and the prescribing patterns in clinical practice in Japan. These consensus statements are intended to present the committee's take on diabetes management in Japan, based on the evidence currently available for each of the issues addressed. It is thus hoped that practicing diabetologists will not fail to consult these statements to provide the best available practice in their respective clinical settings. Given that the persistent dual GIP/GLP-1 receptor agonist tirzepatide was approved in April 2023, these consensus statements have been revised1). In this revision, specifically, tirzepatide was added to the end of [likely involving insulin resistance] of "Obese patients" in Step 1: "Select medications to address the diabetes pathology involved" in Fig. 2. While the sentence, "Insulin insufficiency and resistance can be assessed by referring to the various indices listed in the JDS 'Guide to Diabetes Management.' was mentioned in the previous edition as well, "While insulin resistance is analogized based on BMI, abdominal obesity, and visceral fat accumulation, an assessment of indicators (e.g., HOMA-IR) is desirable" was added as information in order to more accurately recognize the pathology. Regarding Step 2: "Give due consideration to safety," "For renal excretion" was added to the "Rule of thumb 2: Avoid glinides in patients with renal impairment." The order of the medications in "rule of thumb 3: Avoid thiazolidinediones and biguanides in patients with heart failure (in whom they are contraindicated)." to thiazolidinediones then biguanides. In the description of the lowest part of Fig. 2, for each patient failing to achieve his/her HbA1c control goal, "while reverting to step 1" was changed to "while reverting to the opening" and "including reassessment if the patient is indicated for insulin therapy" was added. In the separate table, the column for tirzepatides was added, while the two items, "Characteristic side effects" and "Persistence of effect" were added to the area of interest. The revision also carried additional descriptions of the figure and table such as tirzepatides and "Characteristic side effects" in the statement, and while not mentioned in the proposed algorithm figure, nonalcoholic fatty liver disease (NAFLD) is covered from this revision for patients with comorbidities calling for medical attention. Moreover, detailed information was added to the relative/absolute indication for insulin therapy, the Kumamoto Declaration 2013 for glycemic targets, and glycemic targets for older people with diabetes. Again, in this revision, it is hoped that the algorithm presented here will not only contribute to improved diabetes management in Japan, but will continue to evolve into a better algorithm over time, reflecting new evidence as it becomes available.

Bisphenol mixtures, metal mixtures and type 2 diabetes mellitus: Insights from metabolite profiling.

BACKGROUND: Little is known about the combined effect of bisphenol mixtures and metal mixtures on type 2 diabetes mellitus (T2DM) risk, and the mediating roles of metabolites. METHODS: The study included 606 pairs of T2DM cases and controls matched by age and sex, and information of participants was collected through questionnaires and laboratory tests. Serum bisphenol and plasma metal concentrations were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Widely targeted metabolomics was employed to obtain the serum metabolomic profiles. Conditional logistic regression models were used to assess the single associations of bisphenols and metals with T2DM risk after multivariable adjustment. Additionally, the joint effects of bisphenol mixtures and metal mixtures were examined using quantile-based g-computation (QG-C) models. Furthermore, differential metabolites associated with T2DM were identified, and mediation analyses were performed to explore the role of metabolites in the associations of bisphenols and metals with T2DM risk. RESULTS: The results showed bisphenol mixtures were associated with an increased T2DM risk, with bisphenol A (BPA) identified as the primary contributor. While the association between metal mixtures and T2DM remained inconclusive, cobalt (Co), iron (Fe), and zinc (Zn) showed the highest weight indices for T2DM risk. A total of 154 differential metabolites were screened between the T2DM cases and controls. Mediation analyses indicated that 9 metabolites mediated the association between BPA and T2DM, while L-valine mediated the association between Zn and T2DM risk. CONCLUSIONS: The study indicated that BPA, Co, Fe, and Zn were the primary contributors to increased T2DM risk, and metabolites played a mediating role in the associations of BPA and Zn with the risk of T2DM. Our findings contribute to a better understanding of the mechanisms underlying the associations of bisphenols and metals with T2DM.

HLA-DM and HLA-DO interplay for the peptide editing of HLA class II in healthy tissues and leukemia.

HLA class II antigen presentation is modulated by the activity of the peptide editor HLA-DM and its antagonist HLA-DO, with their interplay controlling the peptide repertoires presented by normal and malignant cells. The role of these molecules in allogeneic hematopoietic cell transplantation (alloHCT) is poorly investigated. Balanced expression of HLA-DM and HLA-DO can influence the presentation of leukemia-associated antigens and peptides targeted by alloreactive T cells, therefore affecting both anti-leukemia immunity and the potential onset of Graft versus Host Disease. We leveraged on a large collection of bulk and single cell RNA sequencing data, available at different repositories, to comprehensively review the level and distribution of HLA-DM and HLA-DO in different cell types and tissues of the human body. The resulting expression atlas will help future investigations aiming to dissect the dual role of HLA class II peptide editing in alloHCT, and their potential impact on its clinical outcome.

Protective effect of Galectin-3 inhibitor against cardiac remodelling in an isoprenaline-induced myocardial infarction in type 2 diabetes.

Type 2 Diabetes mellitus (T2DM) has the potential to impair cardiac function and cause heart failure. We aimed to study the cardioprotective influence of Galactin-3 (Gal-3) inhibitor; modified citrus pectin (MCP) in isoprenaline induced myocardial infarction (MI) in T2DM rats. Forty rats were allocated into 4 groups; groups I and II served as control. T2DM was provoked in groups III and IV by serving them high fat diet followed by a single low dose of Streptozotocin (STZ), then group IV were administered MCP in drinking water for 6 weeks. Groups III and IV were then subcutaneously injected isoprenaline hydrochloride once daily on the last 2 successive days to induce MI. MCP restored echocardiographic parameters with significant decline in Gal-3 area % in cardiac tissue alongside protection against cardiac remodelling. our data showed that there is a protective potential for Gal-3 inhibitor (MCP) against cardiac injury in isoprenaline induced MI in T2DM.

Type 2 Diabetes mellitus (T2DM) has the potential to impair cardiac function and cause heart failure (HF).Gal-3 inhibition with MCP for 6 weeks caused effective protection against cardiac fibrosis, LV dysfunction, and ensuing heart failure progress in type 2 diabetic rats with an isoprenaline-induced myocardial infarction.The defending effect of Gal-3 inhibitor; MCP seems to be exerted by modulating cardiac cell response to injury, through decreasing incidence of cardiac inflammation, oxidative stress, apoptosis and decreased cardiac Gal-3 immuno-reactivity.

Occult coronary microvascular dysfunction and ischaemic heart disease in patients with diabetes and heart failure.

BACKGROUND: Patients with diabetes (DM) and heart failure (HF) have worse outcomes than normoglycaemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischaemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify extent of silent IHD and CMD in patients with DM presenting with HF. METHODS: Prospectively recruited outpatients undergoing assessment into the aetiology of HF underwent inline quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). RESULTS: Final analysis included 343 patients (176 normoglycaemic, 84 with pre-diabetes and 83 with DM). Prevalence of silent IHD was highest in DM (31%), then pre-diabetes (20%) then normoglycaemia (17%). Stress MBF was lowest in DM (1.53±0.52), then pre-diabetes (1.59±0.54) then normoglycaemia (1.83±0.62). MPR was lowest in DM (2.37±0.85) then pre-diabetes (2.41±0.88) then normoglycaemia (2.61±0.90). During follow up 45 patients experienced at least one MACE. On univariate Cox regression analysis MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age and left ventricular ejection fraction the associations were no longer significant. CONCLUSIONS: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for assessment of silent IHD and CMD in patients with DM presenting with HF.