The global prevalence rate of diabetes in 2021 was 6.1% making diabetes one of the top 10 causes of death. Prolonged use of antidiabetic medications is associated with various side effects; therefore, alternative treatment strategies for diabetes need exploration. The antidiabetic properties of Lactiplantibacillus plantarum 2034 was explored both in in vitro and in vivo studies. Secretory metabolites of probiotic L. plantarum 2034 exhibited alpha-glucosidase, alpha-amylase, and lipase inhibitory activities, in vitro. Further, the antidiabetic efficacy of 2034 was evaluated in streptozotocin-nicotinamide-induced diabetic rats. In the therapeutic model, oral administration of L. plantarum resulted in normalization of body weight, fasting blood glucose, total cholesterol (TC), and liver enzymes, and significant (p < 0.05) reduction in insulin and triglyceride (TG) levels. Histological evaluation of pancreas, liver, and kidney showed restoration of normal architecture in probiotic-treated group. Similarly, in a preventive + therapeutic model, 14 days of pre-administration of 2034 in pre, pre + post, and cell-free supernatant resulted in significant reduction in glucose, TG, TC, and liver biochemistry of diabetic rats as compared to untreated diabetic rats. An oral glucose tolerance test showed that the glucose levels normalized within 90 min in all the treated groups. Further, the oxidative stress parameters were also studied that showed that in all the treated groups, the concentration of antioxidant enzymes significantly (p < 0.05) increased as compared to diabetic untreated rats. Thus, administration of L. plantarum 2034 and its metabolites successfully ameliorated hyperglycaemia and hypercholesterolemia in both the models probably due to inhibition of gut enzymes and by increasing the concentration of liver antioxidant enzymes.

BACKGROUND: Diabetes carries an increased risk of cardiovascular disease and thromboembolic events. Upon endothelial dysfunction, platelets bind to endothelial cells to precipitate thrombus formation, however, it is unclear which surface proteins regulate platelet-endothelium interaction. We and others have shown that peri/epicellular (pec) protein disulphide isomerase A1 (pecPDI) influences the adhesion and migration of vascular cells.
OBJECTIVE: We investigated whether pecPDI regulates adhesion-related molecules on the surface of endothelial cells and platelets that influence the binding of these cells in hyperglycaemia.
METHODS: Immunofluorescence was used to assess platelet-endothelium interaction in vitro, cytoskeleton reorganization and focal adhesions. Hydrogen peroxide production was assessed via Amplex Red assays. Cell biophysics was assessed using atomic force microscopy. Secreted proteins of interest were identified through proteomics (secretomics) and targets were knocked down using siRNA. PDI contribution was assessed using whole-cell PDI or pecPDI inhibitors or siRNA.
RESULTS: Platelets of healthy donors adhered more onto hyperglycaemic HUVECs. Endothelial, but not platelet, pecPDI regulated this effect. Hyperglycaemic HUVECs showed marked cytoskeleton reorganization, increased H2O2 production and elongated focal adhesions. Indeed, hyperglycaemic HUVECs were stiffer compared to normoglycaemic cells. PDI and pecPDI inhibition reversed the abovementioned processes in hyperglycaemic cells. A secretomics analysis revealed eight proteins secreted in a PDI-dependent manner by hyperglycaemic cells. Among these, we showed that genetic deletion of LAMC1 and SLC3A2 decreased platelet-endothelium interaction and did not potentiate the effects of PDI inhibitors.
CONCLUSIONS: Endothelial pecPDI regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics.

OBJECTIVE: To describe glucose homeostasis disturbances (dysglycaemia) in very low-birthweight infants (<1500 g) during the admission period and explore associated risk factors.
METHODS: The LIGHT (very low-birthweight infants - glucose and hormonal profile over time) study was a prospective observational cohort study that included 49 very low-birthweight infants admitted to the tertiary neonatal intensive care unit in Umeå, Sweden, during 2016-2019. All glucose concentrations (n = 3515) sampled during the admission period were registered.
RESULTS: Hyperglycaemia >10 mmol/L and hypoglycaemia <2.6 mmol/L were registered in 63% and 55% of the infants, respectively. Onset of dysglycaemia occurred almost exclusively in the first postnatal week. Hyperglycaemia followed 15% of corticosteroid doses given; all were preceded by pre-existing hyperglycaemia. Pre-existing hyperglycaemia was found in 66.7% of hyperglycaemic infants who received inotrope treatment. Upon commencement, 72.5% of antimicrobial treatments given were neither preceded nor followed by hyperglycaemia.
CONCLUSIONS: Dysglycaemia was common in very low-birthweight infants. Daily means of glucose concentrations seemed to follow a postmenstrual age-dependent pattern, decreasing towards term age suggesting a postmenstrual age-dependent developmental mechanism. The primary mechanism causing hyperglycaemia was independent of sepsis, and corticosteroid and inotrope treatments. No hypoglycaemia was registered during ongoing insulin treatment.

暂无摘要。

OBJECTIVE: This retrospective observational study aimed to comprehensively analyse the clinical profile and treatment modalities of patients diagnosed with type 2 diabetes mellitus (T2DM) who were treated at a tertiary care centre.
METHODS: The study included a cohort of 300 individuals who sought medical care at the hospital from January 2023 to January 2024. The analysis primarily examined parameters such as the mean number of anti-diabetic medications per prescription, the proportion of various categories of anti-diabetic medications prescribed, the predominant class and type of anti-diabetic medications prescribed, and the proportion of anti-diabetic medications prescribed from the essential drug lists.
RESULTS: The age distribution demonstrated that 52.0% of participants were above 60 years old, showcasing a substantial elderly representation. Gender distribution emphasized a male predominance at 65.0%, highlighting potential gender-specific implications in type II diabetes. The blood profile analysis of patients with T2DM revealed a range of values for key parameters. Fasting blood glucose levels ranged from a minimum of 101 mg/dL to a maximum of 359 mg/dL, with a mean of 180.01 mg/dl. The comprehensive analysis of anti-diabetic drug utilization, based on the total number of units prescribed, sheds light on the diverse treatment approaches employed for managing diabetes mellitus (DM). Insulin, comprising 31.3% of the total units, plays a pivotal role in glycemic control, with both regular and biphasic formulations contributing significantly at 26.3% and 9.3%, respectively. Among the 300 patients, the overall utilization of anti-diabetic drugs reveals that 38.7% of individuals are using a combination of insulin with oral anti-diabetic drugs, while 61.3% are relying on oral anti-diabetic drugs alone. The most frequently prescribed drug combinations for diabetes management include sulphonylurea with biguanides, emerging as the most prevalent combination with 22 occurrences.
CONCLUSIONS: The study\'s findings contribute valuable insights into the socio-demographic profiles and anti-diabetic drug utilization patterns among diabetes patients.

BACKGROUND: Diabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored.
METHODS: tRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM.
RESULTS: We identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation.
CONCLUSIONS: Hyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM.

BACKGROUND: Clinical endocrinology has observed emerging endocrine complications following COVID-19 vaccination, amidst successful reductions in COVID-19 hospitalizations and deaths. The Pfizer-BioNTech and Moderna mRNA vaccines have demonstrated efficacy. Reports indicate a potential association between SARS-CoV-2 vaccination and diabetes, exploring interactions with ACE-2 receptors and molecular mimicry. Additionally, altered liver and kidney function tests post-vaccination prompt investigation into their role in predicting type 2 diabetes. This study aims to explore these biochemical abnormalities in a case-control, single-centre prospective study.
METHODS: This prospective study aimed to evaluate a total of five hundred healthy donors, out of which 203 qualified for final analysis. Participants were selected based on their vaccination status with a COVID-19 vaccine and prior exposure to the SARS-CoV-2 virus. Donors without prior SARS-CoV-2 infection were excluded from the study. Included participants were adults who had received three doses of the COVID-19 vaccine.
RESULTS: A total of 203 individuals were included in the study, comprising 104 with type 2 diabetes mellitus (T2DM) and 99 without. Demographic characteristics including age, sex, nationality, Rh factors, ABO blood groups, liver function tests (LFT), kidney function tests (KFT), lactate dehydrogenase (LDH), and mineral ion levels were analysed. Among the participants, the distribution based on HbA1c levels showed 47.8% with HbA1c <7% classified as normal, 38.48% with HbA1c 8-10% classified as high, and 16.64% with HbA1c <10% classified as uncontrolled diabetes. Significant findings included a decrease in magnesium levels to 0.77±0.82 mmol/L (p<0.04*), an increase in LDH levels to 420.70±356.26 µL (p<0.01*), and elevated levels of alkaline phosphatase (143.22 ± 142.62 µL, p<0.001), gamma-glutamyl transferase (GGT) (55.70 ± 32.20 µL, p<0.001), and serum bilirubin (9.23 ± 4.87 µmol/L, p<0.001). Creatinine levels were significantly lower at 116.75 ± 101.94 µmol/L (p#60;0.001), while uric acid levels were significantly elevated at 305.92 ± 145.04 µmol/L (p<0.001) in individuals with uncontrolled HbA1c <10%. A majority of these individuals belonged to the O+ blood group.
CONCLUSIONS: This study underscores significant shifts in serum biomarkers and their complex interplay with mRNA-based SARS-CoV-2 vaccination and diabetes, particularly in uncontrolled cases. The findings suggest potential autoimmune reactions triggered by the self-adjuvant properties of mRNA and polyethylene glycol lipid conjugates. Variations observed among different blood groups may correspond to racial disparities influencing molecular mimicry mechanisms. Despite these insights, the underlying pathophysiological mechanisms remain unclear, highlighting the critical need for further research to validate and expand upon these findings.

OBJECTIVE: To assess the long-term glycaemic outcomes, with additional metrics, in adults with type 1 diabetes (T1D) using the Tandem t:slim X2 with Control-IQ technology advanced hybrid closed-loop (AHCL) system.
METHODS: This was a single-centre, retrospective study involving 56 T1D patients who transitioned to the Tandem t:slim X2 with Control-IQ system. The primary and secondary endpoints consisted of variations in time in tight range (TiTR; 70-140 mg/dL) and the glycaemia risk index (GRI), respectively. Additional standardized continuous glucose monitoring (CGM) metrics, mean sensor glucose, coefficient of variation, the glucose management indicator (GMI), HbA1c and insulin daily dose, were also evaluated. Variables were measured at baseline and at 15 days, 3 months, 6 months and 1 year after Tandem t:slim X2 Control-IQ initiation. Glucose outcomes are expressed as mean (standard deviation).
RESULTS: Use of Tandem t:slim X2 with Control-IQ over 1 year was associated with an increase in mean TiTR, from 38.11% (17.05%) to 43.10% (13.20%) (P = .059), and with a decline in the GRI, from 41.03 (25.48) to 28.55 (16.27) (P = .008). CGM metrics, including time in range and time above range, showed consistent improvements. Mean sensor glucose, the GMI and HbA1c decreased significantly over time. After an initial increase, insulin daily dose remained stable throughout the 12 months.
CONCLUSIONS: The results highlight the sustained effectiveness of Tandem t:slim X2 with Control-IQ in improving glycaemic outcomes over 1 year and support the use of this technology for the management of T1D.

UNASSIGNED: Diabetes Mellitus (DM) and hyperglycaemia (HG) have been identified as risk factors for morbidity and mortality in coronavirus disease 19 (COVID-19) infection. However, a detailed study of various categories of HG and the impacts and characteristics of each of these on COVID-19 was considered important to address this metabolic disorder in COVID-19.
UNASSIGNED: This study aimed to describe the patterns of HG and its impact on the clinical outcomes in hospitalised patients with COVID-19 infection.
UNASSIGNED: Data on 1000 consecutive patients with COVID-19 were analysed using Statistical Package for Social Sciences (SPSS) version 20.0 software (SPSS Inc., Chicago, IL, USA).
UNASSIGNED: A total of 1000 patients were included for analysis The overall mean age of the study group was 52.77 + 19.71 with 636 (63.6%) male patients; 261 had mild, 317 moderate, and 422 severe infections; and 601 had HG (New-onset DM 66, known DM 386, steroid-induced HG 133 and stress HG 16). The HG group has significantly higher levels of inflammatory markers and worse outcomes. Blood glucose levels were higher in patients with known DM. The ROC cut-off of total steroids to predict mortality in the HG group was 84 mg versus 60 mg in the normoglycaemia group. The ROC cut-off of FBS to predict mortality in the overall HG group was 165, with AUC 0.58 (95% CI 0.52, 0.63, P = 0.005), whereas that for pre-existing DM and steroid HG were 232 and 166, which were also significant. There was a wide variation in mean glucose levels against time.
UNASSIGNED: HG is an independent predictor of mortality, with the highest significance in the steroid-induced category. COVID-19 morbidity and mortality can be minimised by identifying the blood glucose range for best results and instituting appropriate treatment guidelines.

Diabetes is a chronic medical condition that causes high glycaemic levels, leading to damage to vital organs over time. It is a common disease worldwide, affecting around 422 million individuals living in middle- and low-income countries, which make up most of the population. Unfortunately, diabetes results in 1.5 million deaths annually. Diabetic patients are at a higher risk for developing cardiovascular conditions. Diabetic heart disease constitutes multiple genres, including diabetic cardiomyopathy, coronary artery disease, and heart failure. Hypoglycaemic agents aim to prevent these metabolic issues however some of these are cardiotoxic in nature. In contrast, other hypoglycaemic agents work beyond controlling glycaemic levels with their cardioprotective properties. Given that there is an alarming increase in diabetic heart disease cases universally, we have attempted to review the existing data on the topic and the effects of hypoglycaemic drugs on heart diseases.