Vitamin D deficiency has been implicated in metabolic dysregulation, including insulin resistance and inflammation, commonly observed in patients with type 2 diabetes mellitus (T2DM) and obesity. Evidence on the metabolic impact of vitamin D supplementation in this population remains inconsistent.

To evaluate the effects of high-dose vitamin D3 supplementation on anthropometric and selected metabolic parameters in ambulatory obese patients with T2DM treated with metformin monotherapy.

This 12-week prospective cohort study included 200 patients with T2DM, allocated to a supplementation group (n = 100; vitamin D3 - 4,000 IU/day) or a control group (n = 100; no supplementation). Primary outcome was change in serum 25-hydroxyvitamin D [25(OH)D] concentration. Secondary outcomes included fasting serum glucose (FSG), glycated hemoglobin (HbA1c), blood pressure (BP), serum calcium, and body mass index (BMI). Predictors of failure to achieve target HbA1c ≤ 6.5% were identified using logistic regression.

After 12 weeks, serum 25(OH)D significantly increased in the supplementation group compared with controls (Δ +23.7 vs +1.3 ng/mL; p < 0.001). FSG and HbA1c decreased significantly in the intervention group (Δ -0.4 mmol/L, p = 0.02; Δ -0.6%, p = 0.01, respectively), while no significant changes were observed in systolic or diastolic BP, serum calcium, or BMI. Logistic regression identified higher baseline FSG (OR 1.34, 95% CI 1.12-1.61), longer diabetes duration (OR 1.28, 95% CI 1.07-1.54), and higher BMI (OR 1.21, 95% CI 1.01-1.47) as independent predictors of suboptimal glycemic response.

High-dose vitamin D3 supplementation significantly improved vitamin D status and was associated with modest improvements in glycemic control in obese patients with T2DM, without affecting blood pressure, calcium, or body weight. These findings support vitamin D repletion as a potential adjunctive strategy in diabetes management, while not allowing causal inference, and warrant further confirmation in randomized controlled trials with longer follow-up.

Lower extremity ulcers are a major complication of diabetic disease, often leading to a source of infection for patients. Due to delayed wound healing, ulcers quickly develop into extensive lesions leading to infections that are polymicrobial in nature and highly likely to acquire antibiotic resistance. We present the case of a 44-year-old man with poorly controlled type 2 diabetes mellitus who developed an ulcer on the left lower extremity after an episode of mild pruritus. Failure of early patient presentation to the office resulted in the propagation of infection, including areas of depth and necrosis. The ulcer was initially treated with trimethoprim-sulfamethoxazole (SXT) until cultures revealed a polymicrobial infection of Bacteroides fragilis, group B Streptococcus, and Staphylococcus aureus, with resistance to SXT observed exclusively in S. aureus. Furthermore, the ulcer continued to show signs of infection. As a result, medications were adjusted to metronidazole and ciprofloxacin, combined with meticulous wound care, lifestyle modifications, and optimization of glycemic and lipid control. After treatment modifications, the ulcer showed full-thickness healing. This case highlights the evolving challenge of antimicrobial resistance in skin and soft tissue infections. While SXT is commonly used for infected diabetic ulcers, the increasing prevalence of resistant S. aureus strains emphasizes the importance of culture-guided therapy, careful empiric antibiotic selection, and close patient follow-up. With this holistic, patient-centered approach in managing diabetic ulcers, physicians can catch antibiotic resistance early, preventing serious adverse outcomes and improving quality of life.

Laryngeal tuberculosis (TB) is a rare extrapulmonary manifestation of TB. Patients often present with non-specific laryngeal complaints and may not have pulmonary TB, which was previously almost always associated with laryngeal TB. This case report describes a patient who initially presented with non-specific symptoms of chronic voice hoarseness and dry cough, who was initially diagnosed with pneumonia. Subsequent otorhinolaryngological evaluation was performed, which showed exudative laryngeal lesions with edema and narrowing of the supraglottis and glottis. The patient underwent urgent fiberoptic intubation to secure the airway, followed by a panendoscopy and biopsy of the laryngeal lesions. Microbiological testing and histopathological examination confirmed the diagnosis of laryngeal TB. The patient was also noted to have pulmonary TB involvement on chest radiographs. The patient was noted to have poorly controlled diabetes mellitus that was newly diagnosed, which is a significant risk factor for laryngeal TB. This case report highlights the ease of misdiagnosis and provides clinicians with a review of the epidemiology, clinical characteristics, diagnostic evaluation, and management of laryngeal TB. Additionally, it draws attention to the possibility of acute airway compromise in laryngeal TB, which is not widely reported in the literature. Laryngeal TB remains a relevant differential diagnosis for patients with chronic laryngeal symptoms, and clinicians should not exclude TB as a diagnosis even in developed or non-endemic regions.

Introduction The oral glucose tolerance test (OGTT), though valuable, is underutilized in outpatient settings for the diagnosis of type 2 diabetes mellitus (T2DM). Our study aimed to confirm prediabetes and assess the risk of developing T2DM in individuals with elevated risk, comparing the diagnostic utility of OGTT with fasting plasma glucose (FPG), post-prandial plasma glucose (PPPG), and HbA1C. Methods A hospital-based cross-sectional study was conducted in the Department of General Medicine of a tertiary care hospital in South India, including adults over 18 years with elevated random plasma glucose (RPG) (≥140 mg/dl), FPG (110-125 mg/dl), and HbA1C (5.7-6.4%). After an overnight fast, participants received 75 g of glucose, and venous blood samples were collected at fasting, one hour, and two hours to measure plasma glucose. Results Of the 113 participants, 55.8% (63) were males and 57.5% (65) were overweight or obese (BMI ≥ 23 kg/m²). FPG classified 44.3% (50) as prediabetic and 9.7% (11) as diabetic. While HbA1C categorized 63.7% (72) as prediabetic and 18.6% (21) as diabetic (cutoff >200 mg/dl), the one-hour OGTT categorized 32.7% (37) as prediabetic (cutoff: 155-199 mg/dl) and 44.2% (50) as diabetic. The one-hour OGTT showed greater sensitivity for detecting at-risk individuals. Conclusions The one-hour OGTT, compared to FPG, PPPG, and HbA1C, offers enhanced sensitivity in confirming prediabetes and unmasking T2DM in the prediabetic population. Incorporating the one-hour OGTT into routine screening may improve early diagnosis and intervention, especially in at-risk populations.

The growing burden of type 2 diabetes mellitus among young adults is a global public health problem. This study aimed to explore risk perception of type 2 diabetes mellitus among university students in Jordan and to identify predictors of perceived susceptibility.

A cross-sectional study that used proportional stratified sampling to recruit 496 third year university students in all fields of study at the University of Jordan. Participants answered online self-administered validated Arabic questionnaire that was designed based on the constructs of the health belief model. Data was analyzed using Statistical Package for Social Sciences (SPSS) software.

The participants in this study evidently underestimated their risk of developing T2DM. Only 25% of students believed that they have high potential of developing T2DM in the future. Perceived susceptibility was low to moderate; it scored lowest among all dimensions of risk perception (mean = 2.86 out of 5). Results of t-test and ANOVA showed that perceived susceptibility was higher among students in engineering and science (p = 0.001), males (p = 0.019), with higher income (p = 0.008), overweight (p = 0.026), and students with little knowledge of T2DM (p = 0.027). Results of logistic regression indicated that high income level was the only significant predictor of higher perceived susceptibility (OR = 2.7. 95%CI 1.35, 3.4). Likelihood of taking preventive action was high (mean = 4.15 out of 5).

Results of this study highlight the need for health system governance to commit to integrate national efforts to design culturally sensitive interventions to raise awareness about the risk of T2DM in Jordan, especially among young adult population.

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.