Charcot neuroarthropathy (CN) can result in severe destruction of the foot and the ankle. Additional episodes of acute CN in the same or contralateral foot cause additional burden. This study aimed to explore Australian high-risk foot podiatrists' understanding of recurrent and contralateral CN in individuals with diabetes.

Semi-structured online interviews were conducted. Interviews were audio-recorded and transcribed. Thematic content analysis was used.

Five themes were identified in relation to recurrent and contralateral CN-two were related to potential risk factors: patients and systems and addressing clinical complexity, two were related to preventive interventions: protection as prevention and knowledge and surveillance and one was related to barriers to implementing preventive interventions: financial and personal endurance. The most reported risk factors were reduced adherence to management and lack of knowledge. Many preventive interventions were reported, but there was a lack of consensus on standardised care, and due to significant barriers, these interventions were not frequently used.

This study found that participants perceived a range of potential risk factors for recurrent and contralateral CN. They also reported a variety of preventive interventions; however, due to associated barriers, these were not frequently applied. Further rigorous research is needed to develop evidence-based guidelines.

Diabetic nephropathy (DN) is one of the most prevalent microvascular complications of diabetes mellitus. In the present study, the effects of PLCG1 DN, as well as its underlying molecular mechanisms associated with ferroptosis, were investigated. Single-cell RNA sequencing data and bioinformatic analyses were employed to support these experimental findings. For in vivo experiments, a DN model was established in C57BL/6 mice via streptozotocin injection. For in vitro investigations, NRK-52E cells were exposed to 20 mmol/L d-glucose to induce a DN-like cellular phenotype. PLCG1 mRNA expression levels were upregulated in DN patients, compared with the normal group. Elevated serum PLCG1 mRNA expression in DN patients correlated with increased urinary creatinine (Cre), blood urea nitrogen (Bun), and 24 h urinary microalbuminuria (mAlb) levels. The mRNA and protein expression levels of PLCG1 m in tissues were significantly upregulated in the mouse DN model and high glucose-induced NRK-52E. Single-cell analysis was performed to detect PLCG1 expression in renal cells of the DN model. Additionally, high glucose exposure induced PLCG1 histone acetylation in the DN model. Sh-PLCG1 alleviated DN progression and reduced oxidative stress in the mouse model. Mechanistically, PLCG1 increased mitochondria-dependent ferroptosis in the DN model. PLCG1 is interlinked with LAMP2A and facilitates the ubiquitination of LAMP2A. Specifically, PLCG1 upregulation enhanced K48-linked ubiquitination of LAMP2A protein in high glucose-induced NRK-52E cells. Ultimately, PLCG1 inhibited the LAMP2A/HSPA8 signaling pathway in the DN model. Our study identifies PLCG1 as a novel regulatory target that inhibits the LAMP2A/HSPA8 signaling pathway. This inhibition promotes mitochondrial oxidative stress, which in turn increases cellular ferroptosis and accelerates the progression of DN. Importantly, PLCG1 holds promise as a critical clinical biomarker for diagnosing DN. It may serve as a potential therapeutic target to mitigate glucose-induced ferroptosis, with implications for the management of not only DN but also other diabetes-related complications.

Dupuytren disease (DD) is a benign fibroproliferative disorder affecting the hand. Although diabetes mellitus is a known risk factor, the underlying mechanisms behind this association remain unclear. This study aimed to examine the relationship between glycemic control and DD in type 1 (T1D) and type 2 diabetes (T2D), and to identify other metabolic risk factors influencing DD risk.

In this retrospective registry study, data from the Swedish National Diabetes Register and the Skåne Healthcare Register were cross-linked. In total, 96,039 individuals aged 18 years or older with T1D or T2D were included. Sex-stratified, multivariable logistic regression models calculated associations between HbA1c levels and DD risk. Interaction analyses evaluated whether diabetes duration modified the association between HbA1c levels and DD risk.

Longer diabetes duration consistently increased the risk of DD in both T1D and T2D groups. A trend toward increased DD risk with higher HbA1c levels was seen in T1D (P > 0.05). Higher body mass index was inversely associated with DD in men and women with T2D (P < 0.05). No interaction was observed between HbA1c levels and diabetes duration.

Diabetes duration seems to be a strong and independent risk factor for DD in T1D and T2D. Although a trend toward higher DD risk with elevated HbA1c was observed in T1D, no interaction with diabetes duration was found. A higher body mass index was associated with a lower risk of DD in individuals with T2D.

The saphenous vein (SV) remains one of the most widely used grafts in coronary artery bypass grafting (CABG), and the integrity of the endothelium-a complex structure susceptible to deleterious effects from proinflammatory comorbidities-is a critical factor for graft patency. A 75-year-old patient with hypertension, dyslipidemia, insulin-dependent Type 2 diabetes mellitus, gout, peripheral arterial occlusive disease, and active smoking presented with unstable angina and cardiogenic shock, exhibiting severe coronary artery disease refractory to medical treatment. Emergency CABG was indicated due to the patient's clinical deterioration. During the procedure, the SV was harvested using skin-bridged incisions in an atraumatic manner with minimal handling. Immediately after excision, the SV was maintained at room temperature (∼20°C), and a venous cannula was attached to the distal portion of a 3-cm segment, which was perfused with a fixation solution containing 2.5% glutaraldehyde, 4% paraformaldehyde, and 0.1 M sodium cacodylate buffer (pH 7.4). It was then stored in an isothermal container and transported for scanning electron microscopy (SEM) analysis. SEM revealed significant endothelial damage, with extensive areas of endothelial cell detachment and loss, exposure of the basement membrane and collagen fibers, and-particularly in areas of endothelial denudation-the presence of fibrin aggregates and microthrombi. This case suggests that, in critically ill patients with multiple comorbidities, the SV may exhibit substantial endothelial damage, including microthrombi formation, immediately after surgical excision. These findings are associative and speculative; further studies are needed to explore whether such changes contribute to an increased risk of early venous graft failure. Upon identifying patients at high risk, intensive therapeutic measures should be promptly implemented to address comorbidities and minimize their deleterious effects on the endothelium.

The aim was to carry out a preliminary investigation to identify new biomarkers and test the suitability of the pro-inflammatory nuclear protein, HMGB1, as a potential diagnostic or treatment target for DCM.

Diabetic cardiomyopathy (DCM) is a complex metabolic disease group which manifests in persons diagnosed with poorly managed Diabetes mellitus. This study investigates whether HMGB1 is capable of attenuating the inflammation that manifests from DCM in pre-clinical models of mouse and rat combined.

A systematic review and a meta-analysis were performed by searching 5 electronic databases and retrieving 2979 articles from which 29 qualified as included studies for reporting 37 biomarkers that were grouped into 8 preclinical DCM biomarker models. The standardized mean difference (SMD or the effect size), non-parametric Mann Whitney U test, ROC, correlation coefficient and coefficient of determination were carried out in this evaluation.

28 heterogeneous proinflammatory biomarkers were identified as carrying a significantly high risk of developing DCM out of the total of 37 biomarkers evaluated in forest plots in which, the highest SMD was produced by cardiac troponin (CTPN). 8 significantly high biomarkers (HMGB1, HW/BW, EF%, FS%, BG, TC, TG, NF-kB) were identified out of 37 in the non-parametric Mann Whitney U test in the DCM group compared to the HC. The correlation coefficient between HMGB1 as the independent variable produced a significant negative (ecological) correlation with HR, EF% and TLR4 at p < 0.05.

The ability of HMGB1 in downregulating inflammation or the direct inhibition of HMGB1 using small molecules or blocking of HMGB1/TLR4/NF-kB signalling pathway could be a novel potential mechanism to resolving DCM which requires further investigations.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024597641.

Tuberculosis remains a prevalent and serious chronic bacterial infection worldwide. Despite significant advancements in TB treatment in recent years, it continues to pose a major public health challenge. The onset and progression of TB are closely associated with individuals who are immunocompromised, as most patients also present comorbidities such as HIV, diabetes mellitus, and nutritional deficiencies. Consequently, the development of new, non-toxic immunomodulatory drugs or treatment strategies may offer viable solutions to these issues. Vitamin D not only plays a crucial role in regulating calcium and phosphate metabolism while maintaining bone health but is also a key regulator of the innate immune response against microbial infections. Furthermore, many tuberculosis patients exhibit low levels of vitamin D; thus, vitamin D may represent an important resource for enhancing immune responses against Mycobacterium tuberculosis infections. This review discusses the immune response mechanisms, vitamin D synthesis processes, and metabolic pathways activated in hosts following infection with M. tuberculosis. It emphasizes how vitamin D contributes to immune regulation and its potential role in combating M. tuberculosis infections within the human body. This literature review aims to provide theoretical support for developing new drugs and treatment strategies for clinical management of anti-M. tuberculosis infections.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in T2DM management due to their ability to lower HbA1c, promote weight loss, and offer cardiovascular and renal protection. However, inter-individual variation in therapeutic response has been observed, potentially influenced by gut microbiota composition. A brief review was conducted to explore current evidence on the interaction between GLP-1RAs and gut microbiotatermed the "pharmaco-gut axis." Literature was examined to understand how specific microbial populations affect drug efficacy and insulin sensitivity. Studies suggest that certain gut microbes, including Bacteroides species, Akkermansia muciniphila, and those producing short-chain fatty acids (SCFAs), enhance GLP-1RA efficacy by improving insulin sensitivity and stimulating endogenous GLP-1 secretion. Conversely, dysbiosis characterized by reduced microbial diversity and increased lipopolysaccharide (LPS)-producing pro-inflammatory bacteria correlates with poor therapeutic response. Furthermore, GLP-1RAs may exert beneficial modulatory effects on the gut microbiota itself, indicating a bidirectional relationship. The interaction between GLP-1RAs and gut microbiota introduces a novel pharmaco-gut interface, emphasizing the role of microbial composition in drug response. This emerging concept has the potential to enhance precision medicine in diabetes care by utilizing microbiome profiling to guide GLP-1RA therapy and improve clinical outcomes.

We report a 55-year-old female who presented with choreiform movements in the right upper and lower limbs and uncontrolled blood sugar levels. Magnetic resonance imaging (MRI) of the brain revealed hyperdense lesions, without diffusion restriction or blooming on gradient echo, in the left lentiform and caudate nuclei. The clinical presentation and MRI brain findings pointed towards a diagnosis of diabetic striatopathy (DS). DS, an underrecognized and underdiagnosed condition, primarily affects older women with poorly-managed diabetes mellitus. Effective management of this disorder chiefly depends on maintaining optimal blood glucose levels. After rigorous glycemic control using insulin therapy, the patient's symptoms started to improve, achieving complete remission of symptoms in about a month.

The OMED2 (Optimization of Medication in Elderly with Diabetes) study addresses the effect and implementation of integrating a deprescribing programme (DPP) in general practice. The aim of the DPP is to reduce glucose-lowering medication (SU/insulin) in overtreated older patients. The protocol for this study has been published previously. This statistical analysis plan (SAP) contains a more elaborate outline of the (statistical) methods we plan to use for data analysis.

The OMED2 study is a randomized mixed-methods study with a 2-year follow-up period that compares the effect of the implementation of a DPP in general practice to regular care (control). In this SAP, we report on the (statistical) approaches that we plan to use to address the study objectives. The main objective of the OMED2 study is to examine the effect of the implementation of the DPP on diabetes complications, whereby the total number of diabetes complications related to undertreatment and overtreatment will be summed. Generalized linear mixed models with a Poisson distribution and the DPP as the main determinant will be used to test whether the total number of diabetes complications occurring from the start of the 2-year follow-up until the end of follow-up differs between intervention and control. The incident rate of the number of diabetes complications will be calculated to correct for possible differences in follow-up duration. The model will also include a random effect variable to allow for possible clustering effects by general practice. We will perform intention-to-treat analyses, which include all patients eligible for deprescribing, as well as per protocol analyses, which omit patients who were not deprescribed in the intervention arm. Additionally, approaches to study the implementation of the DPP and the cost-effectiveness of the implementation are outlined in the SAP.

ISRCTN Registry ISRCTN50008265. Registered on 1 November 2024.