Diabetic retinopathy (DR) is the leading cause of vision loss among working-age adults worldwide. AI-assisted automated image reading has effectively alleviated the human resource challenges in large-scale remote screenings, yet there is limited analysis on the impact of complex ocular factors on the diagnostic efficacy of AI.

This study aimed to systematically analyze the impact of multiple ocular factors on the diagnostic efficacy of the EVisionAI system in detecting DR and vision-threatening diabetic retinopathy (VTDR) during large-scale screening of residents with diabetes in resource-limited regions.

This cross-sectional study used a multistage stratified random sampling method to screen residents with type 2 diabetes at primary health centers in resource-limited regions. Data collection involved structured questionnaires (for basic and disease information), hemoglobin A_1c testing, and comprehensive ophthalmic examinations (visual acuity, intraocular pressure, slit-lamp examination, axial length measurement, and fundus photography). Following data collection, 2 ophthalmologists independently graded fundus photographs according to the American Academy of Ophthalmology standards. The influence of various ocular factors on the diagnostic performance of EVisionAI was subsequently evaluated.

Between October 21 and November 12, 2024, 1847 participants with type 2 diabetes (aged 32-91 years) were enrolled, of whom 1748 (94.6%) completed the screening process and 3392 eyes were eligible for DR analysis. Participants had a mean age of 67.17 (SD 8.52) years and mean diabetes duration of 9.13 (SD 6.97) years, with 19.2% (335/1748) having DR and 7.4% (129/1748) having VTDR. Although EVisionAI's diagnostic efficacy was comparable to that of ophthalmologists (sensitivity: 90.61%, 95% CI 87.89%-92.79%; specificity: 98.99%, 95% CI 98.52%-99.31%), some ocular factors-including pupil size, refractive media opacity, and tessellated fundus (TF)-significantly impaired its efficiency. Severe refractive media opacity and TF reduced its sensitivity to 80.95% and 82.86%, respectively, and these factors interfered more with early-stage DR detection than VTDR (97.45% detected), particularly in eyes with severe TF changes (sensitivity decreased to 60.71%). Most notably, severe vitreous degeneration-induced opacity almost invariably led to VTDR misdiagnosis. Additionally, pupil dilation improved the sensitivity of EVisionAI for diagnosing DR (excluding early-stage DR) but had minimal impact on specificity.

EVisionAI achieved high diagnostic accuracy for large-scale DR screening in resource-limited regions, yet its performance for early-stage disease was diminished by severe ocular factors. Optimizing for these factors is therefore essential to maximize its clinical utility in primary care settings with limited specialist access.

Background Albuminuria is an important marker of diabetic kidney disease (DKD) and is associated with adverse renal and cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM). Although sustained hyperglycemia is a recognized contributor to DKD, glycated hemoglobin (HbA1c) does not fully capture short-term glycemic variability. Emerging evidence suggests that hypomagnesemia and altered thyroid function may be associated with albuminuria, but their combined relationships with albuminuria and the possible statistical mediating role of thyroid hormones remain unclear. This study was conducted to identify the associations of albuminuria with glycemic variability, serum magnesium, and thyroid function in T2DM patients. Materials and methods A cross-sectional study included 330 adults aged 30-84 years with T2DM of more than five years' duration. Continuous glucose monitoring (CGM)-derived measures, including mean glucose, glucose standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), were assessed alongside HbA1c, serum magnesium, free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and urinary albumin-to-creatinine ratio (UACR). Associations with albuminuria were examined using univariable and multivariable logistic regression, with additional correlation and exploratory regression-based mediation analysis. Ethical approval and written informed consent were obtained. Results Among 330 participants, 208 (63%) had normal UACR, 98 (29.7%) had microalbuminuria, and 24 (7.3%) had macroalbuminuria. Hypomagnesemia was associated with more than twofold higher odds of albuminuria in univariable analysis (odds ratio (OR)=2.26; 95% confidence interval (CI): 1.38-3.70; p=0.001). In Model IV, which was adjusted for demographic variables, higher HbA1c (OR=1.66; 95% CI: 1.34-2.05; p<0.001), SD (OR=1.63; 95% CI: 1.18-2.26; p=0.003), CV (OR=1.06; 95% CI: 1.01-1.10; p=0.016), and MAGE (OR=1.25; 95% CI: 1.07-1.45; p=0.005) were independently associated with higher odds of albuminuria. In contrast, higher FT3 was inversely associated with albuminuria (OR=0.46; 95% CI: 0.28-0.74; p=0.001). TIR, FT4, and TSH were not significantly associated with albuminuria in univariable analysis. HbA1c was negatively correlated with FT3 (ρ=-0.133; p=0.016). Similarly, SD was negatively correlated with FT3 (ρ=-0.227; p<0.001). Exploratory mediation analysis indicated that FT3 statistically accounted for 6.9% of the association between HbA1c and albuminuria and 21.4% of the association between glucose SD and albuminuria. Conclusion Greater glycemic variability and lower FT3 levels were independently associated with albuminuria in patients with T2DM, while hypomagnesemia was associated with albuminuria in univariable analysis. Exploratory mediation analysis suggested that FT3 statistically accounted for a modest proportion of the associations of HbA1c and glucose SD with albuminuria. These findings indicate that CGM-derived variability measures, alongside magnesium status and thyroid function, may provide complementary information in the assessment of DKD. Prospective multicenter studies are required to clarify the temporal relationships and clinical significance of these findings.

Necrotizing soft tissue infections (NSTIs) are rapidly progressive, life- and limb-threatening emergencies requiring immediate surgical source control. Group B Streptococcus (GBS; Streptococcus agalactiae) is a rare cause of NSTIs in adults. We present a 44-year-old woman with poorly controlled diabetes who developed progressive right foot pain and swelling after minor ankle trauma. Examination showed spreading erythema, crepitus, dusky discoloration, malodor, and a deep plantar wound, accompanied by marked leukocytosis and diabetic ketoacidosis. Computed tomography demonstrated infection extending from the forefoot through the ankle into the anterior compartment of the leg, prompting emergent exploration that confirmed extensive NSTI. Two wound specimens obtained before antibiotics yielded heavy GBS growth, whereas deep intraoperative ankle and leg specimens collected after starting antibiotics grew heavy Streptococcus anginosus and moderate Prevotella species. Despite broad-spectrum antibiotics and debridement, transtibial amputation was required. This case highlights a rare GBS-associated polymicrobial NSTI and emphasizes early recognition of progressive soft-tissue findings despite an apparently minor musculoskeletal injury.

Diabetes Mellitus Type 2 (T2DM) is a significant health concern for Hajj pilgrims, with glycaemic control crucial for their well-being during the pilgrimage. Physical health is key to determining istithaah, including HbA1c and fasting blood glucose tests for prospective Hajj pilgrims with type 2 diabetes mellitus.

This study describes HbA1c and fasting blood glucose levels as indicators of glycaemic control among Indonesian prospective Hajj pilgrims diagnosed with T2DM based on laboratory results from medical check-ups for the 2024 departure in Tangerang City, and assesses their association with demographic factors.

A cross-sectional study analyzed HbA1c from 125 pre-departure medical check-ups of 75 female and 50 male prospective Hajj pilgrims. Data were collected from medical records at a public hospital in Tangerang City and from the Hajj Integrated Computer Health System (SISKOHATKES) application in 2024. Statistical analysis was performed using the Chi-square test or Fisher's exact test, as appropriate.

This study showed that most subjects were female, with the most common age group being 18-59 years (adult). The most prevalent health eligibility (istitaah) status was eligible with assistance. More than 50% of Hajj pilgrims with T2DM had comorbid conditions such as hypertension, cardiomegaly, and hyperlipidaemia. The mean HbA1c level was 9.82 ± 2.2%, with most participants exhibiting uncontrolled glycaemic status (HbA1c >7.5%). Similarly, the mean fasting blood glucose level was 197.0 ± 67.8 mg/dL, with the majority also falling within the uncontrolled range (fasting blood glucose >126 mg/dL). There was no significant correlation between HbA1c levels and age or sex.

The majority of prospective Hajj pilgrims with T2DM are uncontrolled in terms of glycaemic status. These findings require comprehensive assessment and management strategies before, during, and after the Hajj pilgrimage to minimize risk and prevent complications.

Mitochondria are central regulators of cellular metabolism, redox homeostasis, and stress adaptation. Mitohormesis refers to an adaptive response in which mild or transient mitochondrial perturbation activates stress-response pathways that subsequently enhance mitochondrial or cellular resilience; however, persistent or excessive stress can overwhelm adaptive capacity and promote mitochondrial dysfunction and tissue injury. Metabolic diseases, including obesity and type 2 diabetes mellitus, are major risk factors for cognitive decline and dementia, and clinical studies have demonstrated associations between metabolic dysfunction, structural brain abnormalities, accelerated brain aging, and impaired cognitive function. However, direct evidence linking mitochondrial dysfunction to neurodegeneration in humans remains limited, with most mechanistic insights derived from experimental animal models and cultured neuronal systems. Experimental evidence indicates that chronic metabolic stress can disrupt mitochondrial quality control and proteostasis, increase mitochondrial reactive oxygen species production, and promote neuroinflammation and neuronal dysfunction. Conversely, adaptive mitochondrial stress responses can preserve mitochondrial integrity and cellular resilience through coordinated regulation of the integrated stress response, mitochondrial quality-control mechanisms, lysosomal-mitochondrial crosstalk, extracellular vesicle-mediated communication, and inter-organ signaling. In Alzheimer's disease, mitochondrial dysfunction and amyloid-β/tau pathology may interact bidirectionally, potentially generating self-reinforcing cycles of neuronal injury. Lifestyle and pharmacological interventions-including exercise; caloric restriction; nutritional ketosis; and the use of metformin, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists-have been associated with adaptive mitochondrial and metabolic responses involving AMP-activated protein kinase, nuclear factor erythroid 2-related factor 2, mitochondrial biogenesis, mitophagy, and redox signaling. However, evidence that mitohormesis directly mediates their beneficial effects varies substantially across interventions and remains predominantly indirect or hypothesized in humans. Moreover, the discrepancy between encouraging preclinical findings and clinical outcomes highlights important translational barriers, including the lack of validated biomarkers, uncertainty regarding optimal stress intensity and timing, and tissue- and disease-specific differences in adaptive capacity. Collectively, current evidence supports mitohormesis as a conceptual framework for integrating mitochondrial stress adaptation, metabolic dysfunction, and neuronal resilience rather than as an established unifying mechanism underlying neurodegeneration. Defining the conditions under which mitochondrial stress is adaptive, identifying reliable biomarkers of mitohormesis, and determining whether these responses can be safely and effectively modulated in humans will be essential for establishing its therapeutic relevance in metabolic and neurodegenerative diseases.

Gestational diabetes mellitus (GDM) is commonly diagnosed at 24-28 weeks of gestation; however, metabolic susceptibility that precedes dysglycemia may emerge earlier. We examined whether the rate of early pregnancy body mass index (BMI)-derived estimated body fat percentage (eBFP) change was associated with subsequent GDM, and whether this association differed according to an early hepatic-metabolic phenotype defined by the natural log-transformed fatty liver index (FLI_Ln). This secondary analysis used de-identified data from a prospective Korean pregnancy cohort and included 583 singleton pregnant women without pregestational diabetes, of whom 37 developed GDM. eBFP was estimated from BMI and maternal age, and the early-pregnancy eBFP change rate was calculated from pre-pregnancy to 10-14 weeks of gestation and scaled so that each one-unit increase represented a 0.1 percentage-point/week higher change rate. Multivariate logistic regression, restricted cubic splines, threshold analysis, subgroup interaction testing, exploratory mediation analysis, and propensity score-matched sensitivity analyses were also performed. After adjustment for maternal age, parity, pre-pregnancy BMI, a higher eBFP change rate was associated with increased odds of subsequent GDM (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.14-2.21; P = 0.006), with an approximately linear dose-response pattern. The FLI_Ln showed a nonlinear association with GDM, with a data-derived threshold of 2.90. The eBFP change rate-GDM association was evident among women with FLI_Ln ≥2.90 (OR, 1.82; 95% CI, 1.22-2.71; P = 0.004), but not among those with FLI_Ln <2.90 (OR, 0.51; 95% CI, 0.22-1.20; P = 0.123; P for interaction = 0.018). Exploratory mediation analyses suggested that FLI_Ln partially accounted for the observed association, although the magnitude of this mediation was imprecisely estimated. In this secondary cohort analysis, a faster early-pregnancy BMI-derived adiposity change was associated with a higher risk of GDM, particularly among women with an elevated composite hepatic-metabolic phenotype. These findings support an early adiposity-hepatic metabolic susceptibility framework for GDM risk enrichment but require external validation before clinical application.

Vitamin D deficiency is a global health issue linked to musculoskeletal disorders, including osteoporosis and arthritis. Despite its critical role in bone and immune health, large-scale comparisons of vitamin D status between outpatient and inpatient populations remain limited.

This study aimed to compare vitamin D levels in patients with and without arthritis or osteoporosis across outpatient and inpatient settings and evaluate their associations with clinical outcomes.

We performed a retrospective cross-sectional analysis of 37800 adults treated at the Department of Orthopedics in Nanjing Drum Tower Hospital from 2015 to 2020. Serum 25(OH)D concentrations were categorized as normal, low, or deficient. Patients were stratified by diagnosis (arthritis and osteoporosis) and care setting (outpatient vs. inpatient). Statistical comparisons were made using t-tests, Chi-square tests, and log-binomial regression adjusted for age, sex, the alternate musculoskeletal diagnosis, and osteocalcin. Diabetes mellitus was only consistently available for inpatients and was therefore handled as a descriptive inpatient characteristic rather than in the outpatient characteristic and regression models.Adjusted relative risks (RRs) for arthritis and osteoporosis were estimated according to vitamin D status, with normal vitamin D as the reference category, using log-binomial regression adjusted for age, sex, osteocalcin, and the alternate musculoskeletal diagnosis where applicable.

Suboptimal vitamin D status (low or deficient levels) was widespread across both settings, affecting 52% of outpatients and 41% of inpatients. The overall mean 25(OH)D was 26.25 ± 7.14 ng/mL in outpatients and 27.38 ± 6.58 ng/mL in inpatients. Among outpatients, those with arthritis exhibited higher deficiency rates (16.2% vs. 13.6% in non-arthritis) and significantly elevated arthritis risks (RR ranging from1.24 to 1.32). Among inpatients, however, the arthritis analysis was limited by the small number of cases (n=176) and wide confidence intervals (RR for deficiency=1.08, 95% CI 0.65-1.70), so the finding is inconclusive and does not support the association. Deficiencies were particularly pronounced in osteoporosis cases: 26.3% of osteoporotic outpatients were deficient (vs.12.8% controls; RR = 2.79), while inpatients with osteoporosis also showed higher deficiency (13.7% vs. 10.2%; RR = 1.50), with both differences statistically significant (p<0.001).

Vitamin D deficiency was common, particularly among osteoporosis patients in outpatient settings. Associations were strongest for outpatient osteoporosis, while the inpatient arthritis estimates were limited by the small number of cases. These findings suggest that targeted assessment of vitamin D status in patients with osteoporosis or arthritis, rather than universal screening, may help identify individuals at higher risk of deficiency and related musculoskeletal complications.

Prediabetes is increasingly prevalent, and women transitioning through menopause may face a particularly elevated risk of progressing to type 2 diabetes (T2DM). Estrogen deficiency promotes adiposity, insulin resistance, and inflammation, potentially amplifying the metabolic burden of aging. However, the determinants of T2DM in these women remain insufficiently characterized.

This retrospective study included 229 prediabetic women evaluated at a tertiary-care hospital and followed for up to 5.5 years. Prediabetes was defined according to ADA criteria and women were classified as premenopausal (< 51 years), early postmenopausal (51-60 years), or late postmenopausal (> 60 years). Clinical and biochemical variables were analyzed for hazard ratios (HR) of T2DM using Cox regression, and Kaplan-Meier curves.

During follow-up, 18% of premenopausal and 35% of postmenopausal women developed T2DM. Higher BMI predicted T2DM in both groups. In postmenopausal women, IGT (HR: 2.59), hypertension (HR: 3.91), lower HDL-C (HR: 0.96), lower vitamin D (HR: 0.93), and reduced eGFR (HR: 0.97) were independently associated with T2DM. Stratification revealed that early post-menopause carried the highest incidence of T2DM. In early post-menopause, higher BMI and uric acid, and lower vitamin D were independent predictors, whereas in late post-menopause, hypertension and reduced eGFR were the strongest determinants.

Risk Factors associated with progression to T2DM in prediabetic women appear to differ across age-defined menopausal stages. Excess adiposity remains a key factor, whereas early post-menopause is characterized by additional associations with hyperuricemia and vitamin D deficiency. In late post-menopause, hypertension and declining renal function appear to be more prominent. These findings support stage-specific risk assessment and tailored preventive strategies in prediabetic women.

Telehealth can enable supplemental care to young people with type 1 diabetes (T1D) in need of frequent guidance or treatment changes. However, the relative benefits of different telehealth modalities (e.g., synchronous video visits versus asynchronous remote patient monitoring [RPM]) for specific populations remain unclear. We conducted a three-arm randomized controlled trial comparing supplemental monthly video visits or monthly RPM versus usual care over 6 months among young people aged 5-18 years with established T1D and hemoglobin A1c (HbA1c) > 8%. The study cohort of 65 participants was 57% publicly insured, with 54% White and 26% Hispanic/Latino, a mean age of 13.4 years, a T1D duration of 5.8 years, a baseline HbA1c of 9.7%, and high baseline use of continuous glucose monitoring (98%) and insulin pumps (77%). Both study arms experienced high rates of attrition (45% among video participants, 35% among RPM participants). Compared with RPM encounters, video visits were longer (mean: 29.8 vs 17.2 min, p < 0.001) and more likely to cover topics beyond insulin dose adjustments, such as diabetes behaviors, technology use, and emotional support. Intention-to-treat analysis demonstrated a trend (p = 0.06) toward 1.0% lower mean HbA1c at study completion among video participants compared with usual care, adjusting for baseline factors; no significant difference was seen for RPM. Feedback about both interventions was highly positive. These findings suggest that among young people with elevated HbA1c despite using diabetes technology, supplemental synchronous, individualized interactions may be more effective at reducing HbA1c than supplemental data review with asynchronous outreach.

Effective diabetes management in adolescents with Type 1 diabetes is crucial to reduce the risk of long-term complications. However, adolescents show the poorest glycemic outcomes of all age groups. A bihormonal fully closed-loop (FCL) system, which requires no user input, may help address these challenges. In this trial, the performance and safety of a bihormonal FCL system (Inreda® AP) was evaluated in adolescents. The trial was a single-center, randomized, crossover trial in adolescents with Type 1 diabetes aged 12-18 years. The FCL system was compared with the participants' usual diabetes treatment in a home healthcare setting. The trial consisted of two study periods of 2 weeks, separated by a 2-week washout period. The primary endpoint was time in range (TIR; 3.9-10.0 mmol/L). In total, 20 individuals were enrolled and the data from 15 of them were analyzed. Glucose outcome parameters showed significant improvements during the FCL treatment period. Median TIR was 61.3% [interquartile range (IQR): 53.7%-68.2%] in the control period compared with 74.9% (IQR: 73.1-81.0) during the FCL period (p < 0.001). Additionally, other glucose outcomes including time above range (> 10.0 mmol/L) and median blood glucose were significantly improved in the FCL treatment period. To conclude, this trial provides preliminary evidence that treatment with the bihormonal FCL system may improve glucose outcome parameters, with no safety concerns observed in adolescents with Type 1 diabetes over the short study duration. However, future research should focus on long-term trials with larger study populations to confirm these findings and evaluate the long-term effects of bihormonal FCL treatment in adolescents.