Microvascular hypercoagulability is a primary driver of diabetic peripheral neuropathy (DPN). This study aimed to evaluate comprehensive whole-blood viscoelastic profiles using the Sonoclot analyzer across distinct clinical stages of DPN.

This cross-sectional study consecutively enrolled 289 hospitalized patients with type 2 diabetes mellitus (T2DM). Based on the Toronto Clinical Neuropathy Score (TCNS) and nerve conduction studies, participants were classified into non-DPN, subclinical DPN (sDPN), and confirmed DPN groups. Sonoclot-derived parameters were quantitatively assessed. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate diagnostic performance.

Among the 289 participants, 93 (32.2%) were diagnosed with sDPN and 70 (24.2%) with confirmed DPN. CR levels did not differ significantly between the non-DPN and sDPN groups, whereas markedly elevated CR levels were observed in patients with confirmed DPN. After adjustment for age, diabetes duration, HbA1c, BMI, and platelet count, CR remained independently associated with DPN (odds ratio 1.154, 95% CI 1.075-1.239). RCS analysis demonstrated a significant nonlinear association between CR levels and the presence of DPN. ROC analysis identified an optimal CR cutoff value of 31.1 (AUC = 0.729), with a sensitivity of 47.1% and a specificity of 98.9%. The moderate sensitivity suggests limited utility as a standalone screening marker.

Sonoclot-derived CR is independently associated with clinically confirmed DPN. Longitudinal studies are required to clarify the temporal nature of this association.

Diabetes mellitus (DM), which affects over 500 million individuals (7%) globally, is associated with male reproductive dysfunction in more than 15% of affected individuals. The preclinical mechanisms by which hypoglycemic phytochemical compounds alleviate reproductive dysfunction in this population are scattered. A detailed systematic review of the preclinical evidence, with a focus on mechanisms of action and application potential, is currently necessary. The objectives were to analyze preclinical evidence on the therapeutic potential and mechanistic pathways through which hypoglycemic phytochemicals improve male reproductive function in diabetes mellitus.

The protocol was registered in PROSPERO prior to screening, and PRISMA guidelines 2020 were followed. Papers included in the search were published from October 2010 to October 2025 and were identified using the PubMed, Connecting Repositories, and Google Scholar databases.

Only 35 studies published between 2012 and 2025 that investigated improvements in male reproductive dysfunction in preclinical settings were reviewed.

The hypoglycemic phytochemicals improved diabetes-induced reproductive dysfunction through their effects on oxidative stress, sperm parameters, spermatogenesis, testicular morphology, testosterone, follicle-stimulating hormone, and luteinizing hormone. There were variations in the outcomes measured and methodologies. The majority of hypoglycemic phytochemicals reduced reactive oxygen species, which may be inadequate in humans, where there is also a psychological impact on erection.

The review showed that hypoglycemic phytochemicals have the potential to improve male reproductive dysfunction in preclinical models of diabetes mellitus. The synthesis highlights the beneficial effects on glycemic control, sperm quality, hormonal regulation, oxidative stress, and testicular histology via integrated metabolic and reproductive mechanisms. Standardized phytochemicals should be used to study efficacy and safety before clinical trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251230781, identifier CRD420251230781.

Prior investigations have suggested a relationship in which vitamin D may be linked to distal symmetric polyneuropathy (DSPN), but these results are inconsistent. Moreover, few studies have examined the linear relationship between vitamin D levels and the severity of DSPN and no definitive clinical threshold has been identified. This study therefore investigated the connection between the level of serum 25-hydroxyvitamin D [25(OH)D] and the risk and severity of DSPN with special regard to the establishment of a clinically significant cutoff point to classify the risks.

This multicenter cross-sectional study included 569 adults with type 2 diabetes mellitus (T2DM) from four hospitals in Fujian Province, China, between June 2022 and May 2023. Serum 25(OH)D₂, 25(OH)D₃, and total 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). DSPN and its severity were assessed by using a standardized five-item neurological examination and the Michigan Neuropathy Screening Instrument (MNSI). Multivariable logistic regression was applied to examine the relationship between 25(OH)D and DSPN. Propensity score matching (PSM) was performed to minimize baseline imbalances and validate the robustness of the findings. Restricted cubic splines (RCS) were employed to construct a dose-response curve and identify a possible threshold.

Compared with non-DSPN individuals (n = 148), those with DSPN (n = 421) had significantly lower concentrations of 25(OH)D (23.95 ± 5.14 vs. 32.31 ± 5.97 ng/mL) and 25(OH)D₃ (22.88 ± 5.11 vs. 31.19 ± 5.70 ng/mL) (P < 0.001). By contrast, 25(OH)D₂ concentrations presented no evident intergroup difference (P = 0.645). Quartile analysis demonstrated a significant downward trend in the risk of DSPN with increasing 25(OH)D levels (P for trend < 0.001). After controlling for potential confounders, 25(OH)D continued to exert an independent protective effect, and this conclusion remained valid even after propensity score matching. RCS analysis revealed that 25(OH)D and DSPN risk had a linear negative relationship, and a nonlinear relationship was observed with the severity of neuropathy with an turning point at about 26.1 ng/mL. Additional examination revealed that the severity of DSPN increased significantly as the level of 25(OH)D dropped below this point.

25(OH)D was inversely associated with the risk of DSPN, and exhibited a nonlinear relationship with neuropathy severity. Notably, when 25(OH)D levels dropped below 26.1 ng/mL, the severity of DSPN appeared to accelerate markedly. Therefore, 25(OH)D levels have the potential to be a readily accessible and clinically useful indicator to screen and categorize DSPN risk in the early stages.

IgG4-related autoimmune pancreatitis (IgG4-AIP) is a rare autoimmune pancreatic disorder with non-specific clinical manifestations that is often misdiagnosed as acute pancreatitis (AP). Its coexistence with type 2 diabetes mellitus (T2DM) may further complicate recognition of the underlying pancreatic disease.

A 60-year-old male with a 4-year history of T2DM was admitted for diabetic complications manifesting as blurred vision and lower limb numbness. During hospitalization, he developed recurrent epigastric pain associated with elevated pancreatic enzymes and was initially diagnosed with AP. Conventional treatment for AP did not lead to sustained improvement, and amylase and lipase remained persistently elevated. Serum IgG4 was markedly elevated at 13.8 g/L. Imaging findings were unremarkable. Endoscopic ultrasound-guided fine-needle aspiration revealed chronic inflammatory changes. The diagnosis of IgG4-AIP was ultimately established based on the markedly elevated serum IgG4 level, supportive (though atypical) imaging findings, histopathological features, and a favorable response to glucocorticoid therapy. The patient's symptoms improved, accompanied by an overall decrease in serum IgG4 and pancreatic enzyme levels.

In T2DM patients with recurrent abdominal pain and persistently elevated pancreatic enzymes unresponsive to routine AP treatment, IgG4-AIP should be considered. Timely measurement of serum IgG4 and careful integration of imaging, histopathology, and treatment response are important for early diagnosis. Early recognition may prevent misdiagnosis and enable timely initiation of glucocorticoid therapy.

Abdominal pain and gastrointestinal symptoms are common in diabetic ketoacidosis (DKA) and are generally reversible with metabolic correction. However, persistent or worsening abdominal findings should prompt concern for an underlying intra-abdominal emergency. Intestinal ischemia is an uncommon complication of severe hyperglycemic crisis in young patients but may progress rapidly to transmural necrosis due to profound hypovolemia and compromised microvascular perfusion.

A 30-year-old woman with type 1 diabetes mellitus presented with a 3-day history of diarrhea, vomiting, and stupor following insulin omission. Laboratory evaluation demonstrated extreme hyperglycemia (1,869 mg/dL), severe metabolic acidosis (arterial pH 6.83; bicarbonate 2.2 mmol/L; anion gap 20.8 mmol/L), and acute kidney injury. She was managed for a mixed DKA and hyperosmolar hyperglycemic state with intravenous fluids, continuous insulin infusion, and electrolyte replacement. Although her anion gap narrowed, acidemia persisted, renal function deteriorated, and lactate levels increased. She subsequently developed hemodynamic instability requiring vasopressor support, along with progressive abdominal distension and rigidity. Non-contrast abdominal computed tomography revealed pneumatosis intestinalis extending from the ascending to the proximal transverse colon. She underwent emergency subtotal colectomy with end-loop ileostomy; histopathological examination confirmed transmural infarction of the ascending colon with subserosal abscess formation. Following intensive care management and continuous renal replacement therapy, she recovered and was discharged in stable condition.

This case highlights a critical diagnostic challenge: apparent biochemical improvement during a hyperglycemic crisis, such as the narrowing of the anion gap, does not exclude evolving intestinal ischemia. Endocrinologists and critical care physicians must recognize that disproportionate or progressive abdominal signs require prompt imaging and early surgical consultation, even when contrast-enhanced studies are contraindicated.

Native septic arthritis (SA) is rare, with an estimated annual incidence of 2 per 100,000 individuals. It poses a significant clinical burden due to rapid joint destruction and long-term functional impairment. This study presents a retrospective review of native knee, hip, and shoulder SA treated at a single academic medical center. The primary objective was to characterize the clinical, demographic, and microbiologic features of affected patients and to evaluate associations between patient-specific factors and the need for repeat surgical irrigation and debridement (I&D).

This retrospective case series included patients with native SA of the knee, hip, and shoulder treated at a single academic institution between January 1, 2014, and December 31, 2022. Demographics, comorbidities, laboratory data, and culture results were collected for all cohorts. The analysis focused on identifying predictors for reoperation in the knee, hip, and shoulder cohorts.

Among the 62 knee cases, 48% had diabetes, with culture positivity observed in 54%. A formal I&D was performed in 97%, with 32% requiring repeat procedures. Multivariate analysis identified culture positivity (odds ratio [OR] 9.43, P = 0.02) and diabetes (OR 8.0, P = 0.03) as independent predictors of reoperation. Male gender was associated with decreased odds of reoperation (OR 0.18, P = 0.02). In the hip and shoulder cohorts, no significant predictors were found.

Native SA at our institution is associated with significant comorbidities and treatment failure. In this study, diabetes mellitus and culture positivity were independently associated with increased odds of reoperation, whereas male gender was independently associated with decreased odds of reoperation in knee infections. Staphylococcus aureus was the most common pathogen across all joints. These findings highlight the importance of host and microbiologic factors in determining reoperation risk. Further studies are needed to validate these predictors across larger cohorts.

Co-existing asthma and diabetes mellitus (DM) are common, and there has been a debate on whether glucagon-like peptide-1 (GLP-1)-based therapies, such as GLP-1 receptor agonists (GLP-1RA) and inhibitors of dipeptidyl peptidase-4 (DPP-4i), confer benefits in these patients due to their anti-inflammatory effects in chronic inflammatory diseases.

A territory-wide retrospective cohort study was conducted in Hong Kong among adult patients with co-existing asthma and DM to examine the impact of add-on GLP-1RA or DPP-4i on asthma exacerbations, ranging from mild exacerbations managed in outpatient settings to severe exacerbations requiring hospitalization. Adult patients were prescribed DPP-4i or GLP-1RA in year 2018 and for at least 6 months in Hospital Authority of Hong Kong were included. These patients were followed till 31st December 31, 2023. Propensity score matching was performed using optimal full matching, which is a sub-classification-based approach in which treated and control subjects are assigned to matched subclasses.

A total of 3295 patients with both asthma and DM, 3193 treated with DPP-4i and 102 treated with GLP-1RA, were included in the study. There were 1191 (36.1%) male patients with a mean age of 68.0 ± 14.2 years. There were 2531 (76.8%) patients with moderate-to-severe asthma according to Global Initiative for Asthma (GINA) Steps 3 to 5. GLP-1RA-treated patients had significantly lower risks of hospitalized asthma exacerbation (Average Treatment Effect on the Treated (ATT) Mean Ratio of 0.513, p < 0.001), ad hoc outpatient visits with OCS (ATT Mean Ratio of 0.343, p = 0.005), emergency visits (ATT Mean Ratio of 0.378, p = 0.009), and all asthma exacerbations (ATT Mean Ratio of 0.419, p < 0.001) compared with the DPP-4i group.

GLP-1RA, compared with DPP-4i, as an add-on treatment for patients with co-existing DM and asthma was associated with a lower risk of asthma exacerbation. The use of GLP-1RA among diabetic patients with comorbid asthma may be considered though validation in clinical trials is needed.

The oral cavity frequently harbors the earliest clinical manifestations of systemic diseases, yet a persistent knowledge gap exists between dental and medical training programs regarding oral-systemic correlations. Simultaneously, pre-treatment dental evaluation before oncologic therapy and cardiac surgery remains an underutilized step that, when omitted, can lead to osteoradionecrosis, infective endocarditis, treatment delays, and increased morbidity. This narrative review aimed to catalog oral diagnostic clues, organized by organ system, and to synthesize current pre-treatment dental protocols for oncologic and cardiac surgical patients, targeting interdisciplinary trainees in dentistry and internal medicine. A literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library. Clinical studies, systematic reviews, guidelines, and consensus statements published between 2000 and 2025 were included. Oral lesions may precede systemic symptoms in conditions including pemphigus vulgaris, Crohn's disease, leukemia, and Addison's disease. The bidirectional relationship between periodontitis and diabetes mellitus is supported by evidence demonstrating increased rates of type 2 diabetes among affected individuals. Current pre-treatment dental protocols endorsed by major professional organizations recommend comprehensive oral evaluation, elimination of active infection, and defined healing intervals before radiation therapy. Integrating oral examination into systemic disease screening and embedding standardized dental evaluation into oncologic and cardiac surgical pathways may improve early diagnosis, reduce complications, and enhance patient outcomes. Interdisciplinary education and standardized medical-dental consultation templates remain important priorities.

Central nervous system (CNS) fungal infections are associated with significant morbidity and mortality globally, especially in immunocompromised patients. This narrative review aimed to characterise the spectrum of CNS fungal infections in Pakistan. Overall, 14 studies with histologically confirmed diagnoses of CNS fungal infection were included, comprising data on 140 patients. The average age was 38.7 years with male predominance. The most common presenting symptom was headache in 58 (41.42%), followed by visual disturbance in 27 (19.28%) and limb weakness in 22 (15.71%). Among all patients, 31 (22.14%) had a history of diabetes mellitus. Aspergillus was the most frequently isolated pathogen in 46 (32.85%) patients, followed by Mucorales in 42 (30%) patients. Combined medical and surgical management was used in 113 (80.71%) cases. The primary antifungal treatment administered was amphotericin B and voriconazole in 82 (58.57%) and 41 (29.28%) patients, respectively. The surgical management included neuronavigation-guided biopsy in 29 (20.71%), endoscopic debridement in 16 (11.42%), and subtotal resection in 15 (10.71%). The combined medical and surgical management resulted in clinical improvement in 57 (50.44%) patients and mortality in 41 (36.28%) patients. Among the patients given only medical therapy, mortality occurred in 17 (65.38%) patients, and resolution occurred in 2 (7.69%) patients. This review demonstrates that CNS fungal infections in Pakistan often present with nonspecific symptoms. Diabetes mellitus was the most commonly reported comorbidity. The management is multimodal, with combined medical and surgical management required in the majority of patients. Despite treatment, mortality remains high, emphasising the need for earlier diagnosis.

Type 2 diabetes and hypertension frequently coexist and substantially elevate the risk of cardiovascular complications due to interconnected metabolic and vascular mechanisms. The combined presence of these conditions accelerates atherosclerosis, endothelial dysfunction, and inflammatory processes, leading to an increased incidence of adverse cardiovascular events. Existing literature primarily emphasizes individual therapeutic interventions, while limited evidence explores the combined impact of pharmacological treatments and system-level strategies in real-world clinical settings. This study evaluates evidence on therapeutic approaches and integrated care models in relation to cardiovascular outcomes among affected populations. A systematic review with narrative synthesis was conducted without meta-analysis, incorporating 10 studies identified through structured database searches, screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and evaluated using the Newcastle-Ottawa Scale where appropriate. Across the included studies, evidence clustered around three main themes: pharmacological cardioprotection, cardiometabolic risk-factor stability, and integrated care delivery. The findings indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists were associated with more favorable cardiovascular profiles compared to conventional glucose-lowering therapies. Stable glycemic control and reduced hemoglobin A1c (HbA1c) variability were consistently associated with improved cardiovascular outcomes. Hypertension-related findings showed that SGLT2 inhibitors were associated with a lower risk of incident hypertension compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, while multifactorial risk-factor control involving blood pressure, glycemia, lipid parameters, and smoking reduction was associated with fewer cardiovascular events. At the care-delivery level, integrated care frameworks, including HEARTS-aligned approaches, may support healthcare delivery through standardized protocols, multidisciplinary coordination, and continuous monitoring; however, protocol-level HEARTS evidence should be interpreted as implementation-planning evidence rather than proof of improved cardiovascular outcomes. These observations reinforce the importance of adopting a comprehensive, patient-centered approach that integrates both therapeutic advancements and structured healthcare systems for optimal disease management.