Search Results (2,444)

Background: Type 2 diabetes mellitus (T2DM) is one of the most complex metabolic disorders worldwide, with a continuously rising prevalence. T2DM is linked to multiple complications, among which metabolic dysfunction-associated steatotic liver disease (MASLD) has gained increasing recognition. MASLD is the leading cause of chronic liver disease and a major determinant of cirrhosis and hepatocellular carcinoma. This research aimed to estimate the prevalence of MASLD in a single-center outpatient diabetes clinic and explore the associated risk factors. Methods: The study included 170 adults previously diagnosed with T2DM. Data regarding disease duration, metabolic control, demographic characteristics, anthropometric parameters, and comorbidities were retrieved. Laboratory analyses and imaging investigations were conducted to assess liver status and MASLD presence. Results: The prevalence of MASLD was 76.47%. Patients with MASLD presented significantly higher body weight, waist circumference, and body mass index (all p < 0.0001). The MASLD population exhibited longer diabetes duration (p = 0.043) and poor metabolic control. The lipid profile showed higher LDL-cholesterol (p = 0.003) and triglycerides (p < 0.0001) and lower HDL-cholesterol (p = 0.0004). Insulin resistance indices illustrated significant differences, with higher METS-IR and lower eGDR in MASLD patients (both p < 0.0001). Conclusions: MASLD was highly prevalent in the evaluated population. Our findings suggest that MASLD occurrence is mainly associated with obesity, insulin resistance, inadequate glycemic control, and dyslipidemia. All these factors indicate an unfavorable metabolic profile in T2DM patients, underscoring the need for early liver function screening. Full article

Background/Objectives: Onychomycosis is a common fungal nail infection that may contribute to foot morbidity in adults with type 2 diabetes mellitus (T2DM), particularly when neuropathy, peripheral vascular disease, nail dystrophy, local trauma, tinea pedis, or poor glycaemic control coexist. This systematic review and meta-analysis aimed to estimate the prevalence of onychomycosis in adults with T2DM and to explore sources of between-study heterogeneity. Methods: MED-LINE/PubMed, Scopus, Web of Science, LILACS, and EMBASE were searched from 1 January 2000 to 31 January 2026. Observational studies reporting onychomycosis prevalence in adults with T2DM were included. Pooled prevalence was estimated using a random-effects model, and subgroup, sensitivity, and exploratory meta-regression analyses were performed according to diagnostic method, sampling type, geographic region, publication year, and mean age. Results: Eighteen studies, including 6764 participants, were included. The random-effects pooled prevalence was 31.4% (95% CI: 21.7–42.0%), with extreme heterogeneity (I² = 98.8%). Prevalence ranged from 3.8% to 71.7% across studies. Laboratory- or histology-confirmed studies showed a lower pooled prevalence than clinically diagnosed studies, suggesting that clinical diagnosis alone may overestimate onychomycosis prevalence. Exploratory meta-regression indicated that diagnostic method was the main methodological factor associated with prevalence differences, whereas publication year, sampling type, and mean age did not explain heterogeneity. Conclusions: Onychomycosis is frequent among adults with T2DM, but prevalence estimates vary substantially across studies. The pooled estimate should be interpreted cautiously because of extreme heterogeneity and differences in diagnostic definitions. Future studies should use standardised clinical and mycological or histological diagnostic criteria and report diabetes-related risk factors to improve comparability. Full article

Background: While nutritional interventions are pivotal for the prevention and management of gestational diabetes mellitus (GDM), the optimal nutritional strategy remains unclear. Methods: PubMed, EMBASE, Cochrane Library and Web of Science were searched for randomized controlled trials (RCTs). Eligible studies targeted both GDM-diagnosed patients and high-risk cohorts, comparing nutritional interventions with standard controls. Data were extracted and synthesized through network meta-analyses to estimate the standardized mean difference (SMD) or relative risk (RR). The primary outcomes were incidence of GDM, fasting blood glucose (FBG), HOMA-IR, glycated hemoglobin (HbA1c), gestational weight gain (GWG), and cesarean section rate (CSR). Results: A total of 59 trials involving 10,262 women evaluated 24 nutritional strategies. Among high-risk pregnant women, inositol was associated with a reduced incidence of GDM (RR = 0.50, 95% CI: 0.37, 0.68; SUCRA = 84.5%) and lower FBG levels (SMD = −0.42, 95% CI: −0.66, −0.18; SUCRA = 89.8%). For CSR in high-risk pregnant women, blueberry combined with dietary fiber showed a favorable ranking (RR = 0.30, 95% CI: 0.10, 0.90; SUCRA = 97.8%). Among patients with GDM, the Dietary Approaches to Stop Hypertension (DASH) diet showed a significant effect on HOMA-IR (SMD = −2.79, 95% CI: −4.49, −1.09; SUCRA = 95.9%). Plant sterols showed a favorable effect on HbA1c levels (SMD = −1.40, 95% CI: −2.00, −0.80; SUCRA = 95.7%). Fish oil was associated with reduced GWG (SMD = −0.44, 95% CI: −0.76, −0.12; SUCRA = 94.1%). Combined supplementation with magnesium, zinc, calcium, and vitamin D ranked favorably for CSR compared with the control group (RR = 0.44, 95% CI: 0.15, 1.29; SUCRA = 82.1%), but this finding was based on limited evidence. Conclusions: Current evidence suggests that inositol, the DASH diet, plant sterols, and fish oil may play a positive role in the prevention and management of gestational diabetes. However, the effects of interventions with very high SUCRA scores but limited supporting evidence—such as blueberries combined with dietary fiber and magnesium–zinc–calcium–vitamin D supplements—should be interpreted with caution. Well-designed, large-scale randomized controlled trials are needed in the future to further confirm these findings. Full article

Background: Accurate diagnosis and cause of death ascertainment are essential for effective disease surveillance and epidemiological research. This study aimed to validate prostate cancer diagnostic accuracy (PCa) and the accuracy of cause of death information among veterans with type 2 diabetes mellitus (T2DM). Methods: We conducted a retrospective cohort study of veterans with T2DM diagnosed during the baseline period (2008–2009) and followed from 2010 to 2019 using data from the Veterans Health Administration (VHA) Corporate Data Warehouse (CDW). Diagnostic codes and cause of death data were obtained from the Prostate Cancer Data Core (PCDC) and the National Death Index (NDI), which served as the gold standards for validating PCa diagnosis and mortality information in the CDW. Concordance between data sources was assessed using Cohen’s Kappa statistic. Results: Among 763,424 veterans with T2DM, 37,048 (4.9%) were diagnosed with PCa in the CDW and 36,861 (4.8%) in the PCDC, with a concordance rate of 36,361 (98.6% of patients diagnosed in the PCDC). Mortality data from the NDI identified 2723 deaths with PCa listed as the underlying cause of death, of whom 75.4% had a corresponding PCa diagnosis recorded in the CDW. For all-cause mortality, 328,165 veterans were identified as deceased in the CDW Vital Status File (VSF), compared with 326,707 deaths recorded in the NDI. Of these, 324,567 deaths were concordant between the two sources, representing 99.3% of NDI-recorded deaths. Compared with the PCDC, the CDW demonstrated high accuracy for identifying incident PCa diagnosis, with a sensitivity of 98.6% and a specificity of 99.9%. Conclusions: The findings demonstrated a high level of concordance in key outcomes, including PCa diagnosis between the CDW and PCDC, and all-cause mortality between the CDW VSF and NDI. Full article

Background: Studies indicate that depression and cognitive functions are important issues of mental health, a serious health issue worth evaluating with possible alternative non-medical treatment options in MS patients. Aim: The aim of this study was to investigate the effect of practice on fatigue, respiratory closure, depression and cognition in patients diagnosed with MS and whether the benefit of Hatha Yoga training is affected by personality structure. Methods: The study included 25 participants between the ages of 18 and 70 who were diagnosed with MS, with an EDSS of 6 and below and who did not show symptoms of depression and did not use antidepressants. Any previous cerebrovascular disease, hypertension (HTN), diabetes mellitus (DM), thyroid dysfunction, or vitamin B12 deficiency was determined as an exclusion criterion. In the study, patients received Hatha Yoga practice 2 days a week for 8 weeks. The MOCA (Montreal Cognitive Assessment) and Beck Depression Scale, personality analysis test, pulmonary function test, and Fatigue Impact Scale were applied to all patients fulfilling the inclusion criteria at the beginning and after the completion of Yoga practice. Results: According to the results obtained, a statistically significant decrease in Beck Depression Inventory scores (p = 0.020) and a significant increase in MOCA Cognitive Test scores (p < 0.001) were detected following the yoga intervention. Although an increase was observed in respiratory capacity (FVC), this change did not reach statistical significance (p = 0.082). These findings demonstrate that yoga practice significantly improves depression levels and cognitive functions. The relationship between the benefits derived from yoga training and personality traits was evaluated using the participants’ Temperament and Character Inventory (TCI) profiles. Following the yoga intervention, a statistically significant increase was observed in novelty seeking (p < 0.001) and persistence (p < 0.001). Conversely, participants exhibited a significant decrease in harm avoidance post-yoga (p < 0.001). However, no statistically significant changes were found in reward dependence (p = 0.766) or cooperation (p = 0.181) scores after the intervention. Full article

Background/Objectives: Gallbladder emptying is primarily regulated by postprandial cholecystokinin release. In proteinuric glomerular diseases, renal loss of peptide hormones, hormone-binding proteins, or related regulatory proteins may affect biliary motility. However, gallbladder function has not been adequately investigated in individuals with proteinuric glomerular disease. This study evaluated the association between proteinuria and gallbladder emptying in patients with preserved kidney function and biopsy-proven glomerular disease. Methods: This single-center ultrasonographic case–control study with prospective participant enrollment and data collection included 106 participants: 52 patients with biopsy-proven proteinuric glomerular disease and 54 healthy controls without proteinuria. The proteinuric patient group consisted of individuals diagnosed with primary glomerulonephritis or amyloid A (AA) amyloidosis. Acute kidney injury, estimated glomerular filtration rate <60 mL/min/1.73 m², cholelithiasis, liver disease, diabetes mellitus, previous upper gastrointestinal surgery, pregnancy, oral contraceptive use, and recent rapid weight loss were considered exclusion criteria. After an overnight fast of at least 8 h, fasting gallbladder volume was measured by ultrasonography and recorded as baseline volume (V0). Gallbladder volume was measured again 45 min after stimulation with a standardized 40 g chocolate meal and recorded as postprandial volume (V45). Gallbladder volume was calculated using the ellipsoid formula, and gallbladder ejection fraction (GBEF) was calculated as [(V0 − V45)/V0] × 100. GBEF <40% was used as a predefined clinical threshold for impaired gallbladder emptying. In the primary analysis, the association between proteinuria status and GBEF as a continuous outcome was evaluated using a multivariable linear regression model adjusted for age, sex, body mass index, and family history of gallstones. Impaired gallbladder emptying, operationally defined as GBEF <40% for the supportive secondary binary outcome, was examined using multivariable logistic regression model adjusted for the same covariates. Results: Compared with controls, proteinuric patients had significantly higher postprandial gallbladder volume at 45 min: 15,614.04 ± 9148.35 mm³ versus 10,346.89 ± 5254.17 mm³ (p = 0.0003). GBEF was significantly lower in the proteinuria group than in healthy controls: 41.76% ± 19.64 versus 53.10% ± 20.22; mean difference, −11.34 percentage points (95% confidence interval, −19.02 to −3.66; p = 0.0042). Impaired gallbladder emptying was more frequently observed in the proteinuria group: 48.1% versus 27.8% (p = 0.031). In unadjusted analysis, the presence of proteinuria was associated with a 2.41-fold increase in the odds of impaired gallbladder emptying. This association remained statistically significant after adjustment for age, sex, and body mass index: adjusted odds ratio, 2.95 (95% confidence interval, 1.17–7.47; p = 0.022). Among proteinuric patients, GBEF did not differ significantly according to nephrotic versus non-nephrotic proteinuria, serum albumin level, serum total protein level, or histopathological diagnostic subgroup. Conclusions: In individuals with preserved kidney function and biopsy-proven glomerular disease, proteinuria was associated with impaired postprandial gallbladder emptying, and this association persisted after multivariable adjustment. These findings suggest that gallbladder dysmotility may represent a potentially relevant functional feature of proteinuric kidney disease; however, its biological basis and clinical consequences remain to be established. Prospective studies incorporating cholecystokinin measurements, duration of proteinuria, and longitudinal clinical follow-up are needed to clarify these issues. Full article

Maternal uniparental disomy of chromosome 15 [UPD(15)mat] and imprinting defects account for about 30% of cases of Prader–Willi syndrome (PWS). Mosaic UPD(15)mat is rare and may escape routine testing. We describe a 45-year-old male patient in whom persistent clinical suspicion of PWS was not genetically confirmed by repeated methylation-based analyses. Clinical manifestations included neonatal hypotonia with low birth weight, early hyperphagia, severe obesity, short stature, growth hormone deficiency, type 2 diabetes mellitus, dyslipidemia, and MASLD/MASH with compensated cirrhosis. He presented with very mild neurodevelopmental impairment. Following the detection of proteinuria and microalbuminuria from age 22 years, focal segmental glomerulosclerosis was diagnosed upon renal biopsy. A family history of cerebrovascular events was recorded. Combined SNP-array and MS-MLPA analyses across tissues established a diagnosis of PWS due to mosaic UPD(15)mat. The mosaic fraction, estimated by SNP-array, was approximately 10% in peripheral blood and 40% in buccal cells; MS-MLPA detected abnormal methylation only in buccal cells, explaining the previous negative blood-based results. Exome sequencing identified the paternally inherited pathogenic NOTCH3 variant NM_000435.2:c.3016C>T, p.(Arg1006Cys). Subsequent brain MRI showed chronic vascular-type leukoencephalopathy consistent with CADASIL, despite the absence of overt ischemic events in the proband. Collectively, these investigations established a dual molecular diagnosis of PWS due to mosaic UPD(15)mat and NOTCH3-related CADASIL. This report highlights the pivotal role of clinical genetics in assessing the precise diagnosis in rare diseases. With respect to PWS, it demonstrates that mosaicism can lead to a missed diagnosis when the genetic investigation is limited to peripheral blood. In addition, following the diagnosis of CADASIL, and based on the available evidence linking NOTCH3 to renal physiology and disease, we discuss whether NOTCH3-related renal microangiopathy may have contributed to the renal phenotype. However, given the patient’s multiple renal risk factors, FSGS was considered most likely multifactorial, and a causal association with CADASIL cannot be established from this single case. Full article

Background/Objectives: Ultra-processed foods (UPFs) are linked to cardiometabolic disease, but cross-sectional surveys often underestimate or invert these associations due to age structure, diagnosis-related dietary changes, and reporting bias. This study explores the potential influence of these biases and examines cross-sectional associations between dietary proxies and prevalent cardiometabolic conditions using the most recent national data from Spain. Methods: We analyzed the 2023 Spanish Health Survey (n = 21,032). Body Mass Index (BMI) was derived from self-reported weight and height. Hypertension and diabetes were defined as self-reported medical diagnoses. Dietary items were mapped as UPF-rich proxies, processed-meat exposure, protective dietary markers, and beverage comparators. Weighted logistic models were adjusted for sociodemographic and lifestyle factors. Bias-probing analyses included stratification by self-rated health, exclusion of severe chronic comorbidities (n = 4107), and model-based beverage contrasts. Results: Prevalence reached 53.6% for excess weight, 23.9% for prevalent hypertension, and 7.4% for prevalent diabetes. Weekly fast-food consumption was consistently associated with excess weight (OR 1.20, 95% CI 1.07–1.35), obesity (OR 1.28, 95% CI 1.09–1.50), prevalent hypertension (OR 1.18, 95% CI 1.02–1.37), and prevalent diabetes (OR 1.33, 95% CI 1.10–1.61). Excluding participants with severe chronic comorbidities strengthened the fast-food association with prevalent diabetes (OR 1.46, 95% CI 1.17–1.81). Conclusions: Fast food emerged as the most consistent adverse dietary marker co-occurring across all prevalent outcomes, whereas processed meat was specifically associated with prevalent excess weight and obesity rather than prevalent cardiometabolic diagnoses. Stratified and sensitivity analyses provided empirical patterns consistent with age confounding and possible post-diagnosis dietary changes influencing cross-sectional associations, highlighting the need for cautious interpretation in public health surveillance. Full article

Diabetic cardiomyopathy (DCM) is a cardiac condition characterized by various structural and functional abnormalities that are associated with diabetes mellitus. Its development involves multiple factors, among which endothelial dysfunction plays a significant role. To fully describe the relationship between DCM and endothelial dysfunction, we conducted a literature search across several databases, including PubMed, Web of Science, and EMBASE. Our review of DCM research focused on understanding its mechanisms, exploring the methods used to diagnose it, and potential treatment options. Although researchers have made significant progress in DCM diagnosis and treatment in recent years, considerable challenges persist as well. Artificial intelligence (AI)-based multimodal approaches may provide new opportunities for cardiovascular risk stratification and early DCM screening, but DCM-specific models still require external validation before clinical implementation. Regarding treatment options, emerging evidence suggests potential benefits of medications that enhance mitochondrial function and antioxidant properties, as well as anti-inflammatory therapies and lifestyle modifications. Future research should focus on combining different relevant data types, such as genetic and molecular information, to improve the AI tools utilized in medical environments. This study aims to identify novel markers for diagnosing DCM and to devise tailored treatment approaches. These advancements have the potential to improve the prognosis of DCM patients and enhance the identification and management of this condition. Full article

Background/Objectives: Diet is recognized as an important determinant of cardiometabolic health, yet evidence from Middle Eastern populations remains scarce. This cross-sectional study investigated the association between a Prudent dietary pattern and multiple indicators of obesity, type-2 diabetes, and cardiovascular disease in a metabolically healthy Qatari cohort. Methods: Data were obtained from 6919 Qatari adults from the Qatar Biobank study. Participants with diagnosed metabolic disorders, pregnancy, or non-fasting blood samples were excluded. Anthropometric, biochemical, and clinical measurements were collected using standardized protocols. Dietary intake was assessed using a 102-item food frequency questionnaire, and a Prudent dietary pattern was derived through factor loadings analysis. Participants were categorized into low and high intake groups of the Prudent dietary pattern. Associations between the Prudent dietary pattern and cardiometabolic markers were examined using generalized linear models adjusted for age, sex, adiposity, and physical activity with Bonferroni correction applied for multiple testing. Results: After correction for multiple testing, greater adherence to the Prudent dietary pattern was significantly associated with lower fat mass index (β = −0.02, p = 0.0001), fasting insulin (β = −0.05, p = 0.0021), and higher fat-free mass (β = 0.01, p = 5.7 × 10⁻⁵). Conclusions: Overall, in a metabolically healthy Qatari population, greater compliance to a Prudent dietary pattern was favorably associated with fat and muscle mass, and insulin regulation after adjusting for age, sex, BMI and physical activity. These findings support the role of dietary habits in greater cardiometabolic health in Middle Eastern Arab populations. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a sleep condition characterized by intermittent hypoxia, systemic inflammation, and metabolic dysfunction. Contemporary diagnosis criteria depend on polysomnography (PSG), a procedure that is limited by cost and accessibility. Identifying reliable circulating biomarkers may facilitate disease diagnosis and treatment monitoring. Methods: Insulin-like growth factor binding protein-7 (IGFBP-7) has been implicated in pathways relevant to OSA, although its precise role remains elusive. While we previously identified IGFBP-7 as a candidate of interest, in this report, we assessed circulating IGFBP-7 levels in a single-cohort study of 164 participants (124 with OSA, 40 controls) at the Dasman Diabetes Institute. A Type I PSG test was performed in a level 1 sleep laboratory to diagnose sleep apnea. Among the 124 patients with OSA who underwent multilevel sleep surgery (MLS), 67 completed the 3-month postoperative follow-up and were included in the longitudinal analyses. In these participants, we evaluated the apnea–hypopnea index (AHI) at baseline and 3 months after surgery and examined the associations between circulating IGFBP-7 levels, OSA severity indices, and metabolic parameters. Results: Our data revealed a significant increase in IGFBP-7 levels in people with OSA compared to controls (p < 0.001). Importantly, the increase in IGFBP-7 was positively correlated with AHI (r = 0.272, p < 0.001), indicating a potential link with this condition. IGFBP-7 levels declined significantly following MLS (p < 0.001), paralleling improvements in AHI and suggesting responsiveness to therapeutic intervention and a reduced hypoxic burden. IGFBP-4 levels increased significantly in patients with OSA (p = 0.006) but were not correlated with IGFBP-7. The receiver operating characteristic (ROC) analysis identified IGFBP-7 with a cut-off value of 14,003.21 pg/mL as a potential biomarker for OSA, with moderate performance (AUC = 0.722, 95% CI: 0.636–0.808; sensitivity 73%, specificity 84%). Notably, combining IGFBP-7 with IGFBP-4 resulted in a modest improvement (AUC = 0.755). Conclusions: Our data suggest that IGFBP-7 shows a modest association with OSA severity and may have exploratory value as part of a multi-marker or risk-stratification approach. Further large-scale and longitudinal studies are warranted to extensively explore the potential utility of IGFBP-7 within multi-marker approaches. Full article

Background: Non-group 1 pulmonary hypertension, also known as secondary pulmonary hypertension (SPH), is predominantly observed among females. However, there is a significant lack of data concerning factors associated with hospitalization among patients diagnosed with SPH. This study aims to provide clinicians with vital insights for the identification of high-risk groups and for the more effective management of contributory risk factors within the female population affected by SPH. Methods: Using the 2019 National Inpatient Sample, we identified female admissions with SPH (n = 648,190), accounting for 3.8% of the total 17,236,228 female admissions. An Artificial Neural Network (ANN) analysis was conducted to evaluate predictive factors. We randomly allocated 3,319,543 patients into training and testing datasets at a ratio of 70:30, comprising 2,323,696 (70%) for training and 995,847 (30%) for testing, to calibrate and validate the performance of the ANN algorithm. Model performance was assessed by comparing misclassification rates between training and testing sets and by the area under the receiver operating characteristic curve (AUC); only internal validation was performed. Results: Females hospitalized with SPH were generally of older age, with a median of 75 years compared to 58 years, and more frequently identified as White (67.7% versus 65.5%) or Black (20.5% versus 15.5%) relative to those without SPH. They also demonstrated a higher prevalence of most atherosclerotic cardiovascular disease (ASCVD) risk factors or their equivalents, including complicated hypertension (50.6% versus 17.8%), diabetes with chronic complications (30.6% versus 13.7%), and hyperlipidemia (50.8% versus 29.2%), as well as other comorbidities such as COPD (43.4% versus 20.2%) and CKD (43.3% versus 14.0%), and exhibited increased all-cause mortality (4.5% versus 1.8%) (p < 0.001). Our ANN model achieved an AUC of 0.823, indicating good predictive capability. The rates of incorrect predictions were comparable in both the testing and training cohorts, at 3.8% each. The factors most strongly associated with a coded SPH diagnosis included age at admission, complicated hypertension, chronic kidney disease, chronic obstructive pulmonary disease, uncomplicated hypertension, prior VTE, race, arthropathies, and AIDS. Conclusions: Our ANN model identified demographic and comorbidity factors associated with a coded SPH diagnosis among hospitalized females, with good discrimination (AUC = 0.823). Because the model classifies the presence of an existing diagnosis rather than predicting future hospitalization, and was validated only internally, external and prospective validation is required before clinical application. Once validated, these factors could support individualized, sex-specific risk stratification for high-risk female populations, consistent with the goals of personalized medicine. Full article

Background: This study aimed to determine the prevalence of osteosarcopenia and evaluate the diagnostic performance of phase angle, derived from bioelectrical impedance analysis, in identifying osteosarcopenia among older adults with type 2 diabetes mellitus. Method: A cross-sectional study was conducted with 147 participants aged 60 years or older, recruited from an outpatient clinic in Thailand between during 2024. Osteosarcopenia was diagnosed when criteria for both sarcopenia, defined by low skeletal muscle mass and either reduced handgrip strength or impaired physical performance, and osteoporosis, defined by a T-score of −2.5 or lower on dual-energy X-ray absorptiometry, were met. Participant characteristics, physical function, laboratory values, and body composition data were collected. Univariable Firth’s penalized logistic regression identified low body mass index and a lower phase angle as independent predictors of osteosarcopenia. Results: The overall prevalence of osteosarcopenia was 7.5 percent. Receiver operating characteristic curve analysis showed strong diagnostic performance of phase angle, with an area under the curve of 0.865. A cutoff value of less than 4.0 degrees achieved 100% sensitivity, 62.5% specificity, and 100% negative predictive value. These findings suggest that phase angle may be a practical, noninvasive screening tool for identifying older adults with type 2 diabetes mellitus who are at risk for osteosarcopenia. Its application in routine clinical settings could enable earlier intervention and reduce long-term complications associated with musculoskeletal decline in this vulnerable population. Full article

Background: Type 1 diabetes (T1D) is a complex autoimmune disease demonstrating substantial heterogeneity in age of onset, residual C-peptide levels, clinical outcomes, and therapeutic response. Although the autoimmune classification of T1D has traditionally relied on detection of autoantibodies indicating B-cell involvement, studies targeting total CD3⁺ T cells have underscored the importance of T-cell regulation. Th40 cells, a pathogenic subset of CD3⁺ T cells, first identified in NOD mice, become significantly increased during diabetogenesis. Human subjects with T1D exhibit variable but significantly elevated Th40 levels in peripheral blood. Methods: To target pathogenic effector Th40 cells, we developed OPT101, a 15-mer peptide, and found that it interacts with CD40 in association with an activated integrin, identifying a novel inflammatory receptor complex. We conducted a phase 1b, double-blind, first-in-human clinical trial to evaluate OPT101 and met the primary objectives of safety and tolerability. Results: OPT101 generated only Grade 1 and 2 adverse events. Across eight doses, administered over six weeks, no product-related immune suppression was observed. Secondary objectives included immunologic outcomes and potential efficacy. Subjects with higher Th40 levels had low or undetectable C-peptide, higher (>7.0%) HbA1c, and elevated inflammatory cytokines. Th40 levels were significantly higher in subjects diagnosed before age eighteen. OPT101 treatment significantly reduced Th40 percentages without cell ablation, increased Treg levels, and decreased inflammatory cytokines. Serum blood glucose levels and HbA1c were significantly reduced by visit 8 in treated subjects. In two subjects, 11 and 13 years post-diagnosis, with undetectable C-peptide at screening, C-peptide became detectable post-treatment. Conclusions: OPT101 proved safe and effective in human T1D subjects with only mild and a few moderate adverse events. In this short-term study, OPT101 improved beta cell functions thus warranting further exploration. Full article

Background: Functional impairment is common among older adults with diabetes, but multidimensional machine learning classification in this population remains underexplored. This study compared machine learning algorithms for identifying concurrent functional impairment among older adults with self-reported physician-diagnosed diabetes. Methods: This cross-sectional study included 1213 adults aged ≥ 65 years from the nationally sampled 2015 China Health and Retirement Longitudinal Study cohort. Functional impairment was defined as limitations in ≥2 activities of daily living or instrumental activities of daily living. Training set feature selection yielded 18 input features. Eight algorithms were evaluated in a held-out internal test set. Repeated stratified nested 10-fold cross-validation with five repeats assessed stability conditional on the locked feature set. SHAP assessed feature contributions and ranking stability. Results: Functional impairment was present in 34.21% of participants. Random forest achieved the numerically highest test-set AUC (0.774; 95% CI, 0.714–0.833), with sensitivity of 0.512 and a Brier score of 0.181. Its advantage over other models was modest. Under repeated nested cross-validation, random forest achieved a mean AUC of 0.808 ± 0.043 and a mean Brier score of 0.166 ± 0.016. SHAP rankings were stable (Kendall’s W = 0.901); leading contributors included depressive symptoms, self-rated health, 2.5-m walking test completion time, distance vision, history of falls, executive function, and bilateral grip strength. Excluding direct physical performance inputs retained most discrimination but modestly reduced threshold-dependent performance. Conclusions: Random forest provided the most favorable overall internal performance for classifying concurrent functional impairment, although sensitivity remained modest. External and prospective validation is required before clinical implementation. Full article