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An Augmented Likelihood Approach Incorporating Error-Prone Auxiliary Data Into a Survival Analysis.3 weeks agoIn this big data era, we can readily access extensive clinical data from large observational studies or electronic health records (EHR). Data accuracy can vary according to the measurement method. For example, clinical variables extracted by automated computer algorithms or obtained from participant self-reported medical history can be error-prone. Precise data, such as those obtained from a chart review or a gold standard diagnostic test, may only be available on a subset of individuals due to cost or participant burden. We propose a method to augment a regression analysis of a gold standard time-to-event outcome with available error-prone disease diagnoses for the setting where the gold standard is observed on a subset. The proposed model addresses left-truncation and interval-censoring in time-to-event outcomes while leveraging information from the self-reported disease diagnosis in a joint likelihood for the gold standard and error-prone outcomes. The proposed model is applied to the Hispanic Community Health Study/Study of Latinos data to quantify risk factors associated with diabetes onset.DiabetesAccessCare/ManagementAdvocacy
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Clinical characteristics of Tolosa-Hunt syndrome in patients with diabetes mellitus.3 weeks agoDiabetes mellitus (DM), a globally prevalent metabolic disease, affects the nervous system through multiple mechanisms, leading to cranial neuropathies. Tolosa-Hunt syndrome (THS) is a rare disorder that, when occurring in diabetic patients, may present with clinical manifestations that overlap with diabetic cranial neuropathy (DCN), increasing the risk of misdiagnosis and delaying corticosteroid treatment. This study aims to systematically analyze the clinical characteristics of THS in diabetic patients and explore optimal management strategies.
This study conducted a retrospective analysis, integrating data from previously published cases and cases diagnosed at our center. Inclusion criteria were based on the diagnostic standards for THS outlined in the ICHD-3, while cases with other potential causes of headache and ophthalmoplegia were excluded. Data collected included baseline characteristics, clinical manifestations, treatment regimens, and therapeutic outcomes. Statistical analysis was performed using Fisher's exact test, t-test, and Wilcoxon rank-sum test.
A total of 19 cases of diabetes-associated THS were included (11 males, 8 females), with males presenting at a significantly younger age than females (P = 0.041). All patients experienced severe headaches, 89.47% had ptosis, 94.73% exhibited ophthalmoplegia, and 15.79% presented with facial sensory disturbances. Eight patients were initially misdiagnosed with DCN and received neurotrophic therapy without improvement, but they responded rapidly to corticosteroid treatment. All patients showed significant symptom improvement within six days of corticosteroid administration. Methylprednisolone and dexamethasone demonstrated therapeutic effects comparable to prednisone, though symptom resolution was slightly delayed in the prednisone group.
The clinical features of diabetes-associated THS include severe headache, ptosis, and ophthalmoplegia, which can be easily confused with DCN. Corticosteroid therapy demonstrated high efficacy in this cohort. Clinicians should consider the possibility of THS in diabetic patients presenting with ptosis and ophthalmoplegia to avoid misdiagnosis and ensure timely corticosteroid treatment, thereby improving patient outcomes.DiabetesCare/Management -
Noninvasive subterahertz glucose monitoring using a communication inspired eye diagram.3 weeks agoThe global prevalence of diabetes mellitus (DM) continues to rise, highlighting the need for noninvasive, painless continuous blood glucose monitoring to support disease management and reduce long-term complications. Here, we report noninvasive subterahertz (sub-THz) glucose monitoring using communication-inspired eye diagram (sub-THz GlucoEye). The method detects distortion in the modulation pattern of sub-THz carrier signals reflected from the fingertip, resulting from relaxation time variations in the hydration water surrounding glucose molecules. These distortions are analyzed using multivariate regression analysis, based on variations in the modulation pattern's performance parameters represented in the three-dimensional eye diagram. Compared to conventional THz spectroscopy, which only measures THz radiation absorption, the sub-THz GlucoEye system shows enhanced linear correlation (R2 = 0.98) between glucose-dependent features from modulation pattern changes and venous blood glucose concentrations. Results indicate strong consistency between glucose dynamics in venous blood and those at the fingertip during the mixed meal tolerance test, validated by 100% of glucose readings falling within Zones A and B based on Clarke's error grid analysis. This approach offers opportunities for real-time DM management and biomarker detection in future 6G integrated sensing and communication. Registry: Clinical Research Information Service, TRN: KCT0008820, Registration date: 17 June 2023.DiabetesCare/Management
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Diagnostic Value of Exome Sequencing in Isolated Polyhydramnios.3 weeks agoTo evaluate the diagnostic yield of exome sequencing (ES) in isolated polyhydramnios.
This retrospective study included 40 cases of isolated polyhydramnios. All patients underwent screening for gestational diabetes mellitus (GDM) and chromosomal microarray analysis (CMA). ES was performed in CMA-negative cases, along with targeted testing for spinal muscular atrophy, myotonic dystrophy type 1, and Prader-Willi syndrome.
Pathogenic or likely pathogenic variants were identified in 7 cases, yielding a 17.5% diagnostic rate. Diagnostic yield was 12% (2/17) in mild cases and 22% (5/23) in moderate-severe cases. Diagnoses included Bartter syndrome (KCNJ1, BSND, MAGED2), Noonan syndrome (RIT1), Osteopathia Striata with Cranial Sclerosis (AMER1), and AUTS2-related neurodevelopmental disorder. In addition, one case was diagnosed postnatally with myotonic dystrophy 1. Two ES-positive cases had concurrent GDM. Postnatal follow-up showed normal development in 85% of live-born infants, with a few cases of global or speech delay.
ES yields a substantial diagnostic benefit in isolated polyhydramnios, including mild cases and those with GDM. These findings support incorporating ES into the diagnostic approach for isolated polyhydramnios.DiabetesCare/Management -
Eleutheroside B liposomes ameliorate type 2 diabetes mellitus by modulating glucose and lipid metabolism: A metabolomic study.3 weeks agoEleutheroside B (EB), a bioactive compound from Acanthopanax senticosus, has notable hypoglycemic effects. However, its low solubility and limited bioavailability constrain clinical application.
This study aimed to develop novel Eleutheroside B liposomes (EB-LIP) to overcome these limitations and evaluate their therapeutic efficacy in a type 2 diabetes mellitus (T2DM) mouse model. We also examined the molecular mechanisms underlying the improved metabolic effects of EB-LIP, focusing on key signaling pathways in glucose and lipid metabolism.
EB-LIP was synthesized using the ethanol injection method, a process optimized to enhance EB solubility and stability. Therapeutic efficacy was assessed in a T2DM model induced by a high-fat, high-sugar diet in combination streptozotocin. Mice received varying doses of free EB or 100 mg/kg EB-LIP via gavage. We measured blood glucose, lipid profiles, and insulin sensitivity. Histopathological examination assessed tissue damage in major organs. Liver metabolomics identified differential metabolites and predicted altered regulatory pathways. Complementary in vitro studies using high glucose-induced C2C12 cells validated molecular effects, focusing on AMPK signaling pathway and GLUT4 expression.
EB-LIP achieved high encapsulation efficiency (85.90%) and may improve EB solubility and stability. Administration of EB-LIP at 100 mg/kg elicited a stronger hypoglycemic effect compared with the free EB administered at an equivalent dose, and also significantly improved lipid metabolism, and alleviated tissue damage associated with T2DM. Metabolomic analysis identified 303 differential metabolites and revealed that EB-LIP modulated key metabolic pathways, including the AMPK signaling pathway, PPAR signaling pathway, insulin resistance, and glycerophospholipid metabolism. In vitro experiments confirmed that EB-LIP enhances AMPK phosphorylation and GLUT4 expression, improving insulin resistance.
EB‑LIP may improve the bioavailability of EB and exert its antidiabetic effects via multi‑target and multi‑pathway mechanisms. This study supports developing phytochemical-based nanomedicines for complex metabolic diseases.DiabetesDiabetes type 2Care/Management -
CD38 knockout attenuates type 2 diabetic renal injury by downregulating p53 and Bax via the ERK/JNK signaling pathway.3 weeks agoDiabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD), imposes substantial burdens on patients' health and socioeconomic status. Although current therapies targeting blood pressure, glycemic control, and the renin-angiotensin system provide partial relief for DN, their efficacy remains limited. CD38, a 46-kilodalton type II transmembrane glycoprotein, is reported involved in the development of diabetes mellitus. However, the specific role and molecular mechanisms of CD38 in DN pathogenesis require further elucidation. This study aims to investigate these mechanisms.
Analyze the expression of CD38 in DN through the GEO database.Type 2 diabetic mouse models were established by using high-fat diet and streptozocin (STZ) injection. Four groups of mice were used in this experiment: WT group, DM group, CD38-/- group and CD38-/-+DM group. Body weight and fasting blood glucose were monitored longitudinally. After Post-euthanasia, kidney weight and body weight were weighed, then calculated kidney weight/body weight ratio. Renal tissues underwent histopathological evaluation (H&E, PAS, PAM staining) and molecular analyses (immunohistochemistry, RT-qPCR, Western blot).
CD38 expression was significantly higher (P < 0.05) in DN than in normal humans. And CD38 deletion ameliorated renal histopathological injury in type 2 diabetic mice in H&E staining, glycogen staining, PAM staining. RT-qPCR and Western blot results showed expressions of p53 and Bax in kidney tissues of CD38-/-+DM group mice was significantly decreased (P < 0.05) and Bcl-2 was significantly increased (P < 0.01) compared with that of the DM group mice. Bax expression was decreased and Bcl-2 expression was increased in the renal tissues of mice of CD38-/-+DM group when compared with mice in the DM group in immunohistochemical staining. CD38 deletion could alleviate ERK, JNK and p38 of MAPK signaling pathway(P < 0.05). Inhibition of ERK and JNK in high glucose condition ameliorated apoptosis by down-regulating p53 and Bax (P < 0.05).
CD38 deletion regulated body weight and fasting blood glucose, improved renal histopathological injury and apoptosis by inhibiting MAPK signaling pathway; CD38 deficiency alleviates diabetic nephropathy by inhibiting MAPK/p53-mediated apoptosis, highlighting its role as a potential therapeutic target.
Not applicable, and this study does not yet involve clinical data.DiabetesCare/Management -
Thermosensitive porcine acellular dermal matrix hydrogel loaded with umbilical cord mesenchymal stem cell-derived exosomes for diabetic wound healing repair.3 weeks agoPatients with type II diabetes mellitus (DM) often experience severely impaired skin wound healing due to hyperglycemia-induced microvascular dysfunction, peripheral neuropathy, and persistent inflammation, creating an urgent need for new therapeutic strategies. Here, we combined extracellular exosome technology and sol-gel technology to construct a thermosensitive porcine decellularized extracellular matrix (dECM) hydrogel loaded with umbilical cord mesenchymal stem cell-derived exosomes (EXO) for achieving effective type II diabetic wound healing. Results showed that EXO exhibited a typical cup-shaped morphology (average size:122.3 nm) and specific protein expression. Porcine acellular dermal matrix (ADM) had a 94.3 % decellularization rate. The prepared hydrogel demonstrated good injectability, thermosensitive gelation (rapid at 37 °C), porous structure, controllable degradability, and sustained EXO release (≈90.65 % within 72 h). In vitro, the dECM contained EXO (dECM@EXO) hydrogel was non-cytotoxic, promoting L929 cell survival, HaCaT cell proliferation/migration (24-h rate: 85.38 %), and tube formation of endothelial cells. In type II diabetic rats with full-thickness skin wounds, its 14-day healing rate was 97.4 ± 2.6 % (significantly higher than other groups). Immunohistochemical results revealed that dECM@EXO increased the density of CD31+ blood vessels and the proportion of CD206+ M2-type macrophages, decreased the expression of CD68+ macrophages and HSP70, and enhanced the proliferation rate of Ki67+ cells. Transcriptome sequencing analysis demonstrated that dECM@EXO upregulated genes related to pathways such as PI3K-Akt and ECM-receptor interaction to promote cell proliferation and angiogenesis, while downregulating genes related to insulin resistance and glucose metabolism to improve the local microenvironment. Through the synergistic effect of "extracellular matrix hydrogel carrier - exosomes", this study promotes diabetic wound healing from multiple dimensions including anti-inflammation, angiogenesis, and metabolic regulation, providing a new strategy for the clinical treatment of DM wounds.DiabetesCare/ManagementPolicy
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Risk factors of metabolic dysfunction-associated fatty liver disease in people living with HIV receiving antiretroviral therapy.3 weeks agoThis study aimed to identify risk factors associated with the onset and progression of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in People Living with Human Immunodeficiency Virus (PLWH).
Clinical and laboratory data were retrospective collected at 6 months, 1, 1.5, 2, and 3 years after ART initiation. Multivariable logistic regression was employed to identify MAFLD risk factors and evaluate ART's influence.
Among the 740 participants (95% male, mean age 36.58 ± 13.93 years), with an average ART duration of 3.33 ± 4.56 years. Laboratory data at 6 months showed a CD4 count of (356.95 ± 98.76) cells/mm3, body mass index (BMI) of (22.87 ± 7.47) kg/m2, triglycerides (TG) of (1.53 ± 0.98) mmol/L and low-density lipoprotein cholesterol (LDL-c) of (2.45 ± 0.71) mmol/L. MAFLD detection rates by Hepatic Steatosis Index (HSI) and Zhejiang University indices (ZJU) increased with longer ART duration. Patients with>10% weight gain showed a notable rise from 48.80% at baseline to 87% after 3 years of ART. Independent risk factors for MAFLD included female, type 2 diabetes mellitus (T2DM) prior MAFLD, baseline BMI>24 kg/m2 and TG≥1.7 mmol/L, weight gain of 5-10% or >10% within one year, BMI≥24 kg/m2 and TG≥1.7 mmol/L at year 1. Protective factors included age>65 years, AZT and 3TC-based therapies.
The prevalence of MAFLD as assessed by the HSI and ZJU indices increases steadily with ART and is strongly related to weight gains. These findings validate the effectiveness of these non-invasive tools for identifying key risk factors and underscore the necessity of continuous weight monitoring in contemporary ART-treated patients.DiabetesDiabetes type 2Care/Management -
Prevalence and predictors of ambulatory blood pressure monitoring-detected hypertension in children and adolescents with type 1 diabetes.3 weeks agoHypertension accelerates both microvascular and macrovascular complications in patients with diabetes. Despite the growing burden of diabetes and cardiovascular risk, data from low-resource countries on 24-h ambulatory blood pressure monitoring (ABPM)-detected hypertension in children and adolescents with type 1 diabetes mellitus (T1DM) remain limited.
This cross-sectional study enrolled Thai children and adolescents with T1DM aged 8-18 years to perform 24-h ABPM. Clinical data included current diabetes status (HbA1c level and insulin regimen) and metabolic parameters (body mass index [BMI], waist-to-height ratio, and lipid profiles). Historical diabetes data and glycemic control over the previous year were retrospectively reviewed. Hypertension was defined according to the 2022 American Heart Association guidelines. Logistic regression analysis was used to identify independent predictors of ABPM hypertension.
A total of 100 patients were included, with a median age of 13.9 years (interquartile range [IQR]: 11.7-15.9) and a median diabetes duration of 5.1 years (IQR: 2.1-7.3). ABPM detected hypertension in 37% of patients. The majority (78.4%) exhibited hypertension during nighttime, and isolated nocturnal hypertension was present in 32.4% of ABPM hypertension cases. Multivariable analysis identified male sex (adjusted odds ratio [aOR] 3.00; p = 0.02), and obesity (BMI Z-score > 2) (aOR 2.72; p = 0.04) as independent predictors of ABPM hypertension.
ABPM-detected hypertension is common among Thai children and adolescents with T1DM. In resource-constrained environments, ABPM screening should be considered in high-risk patients, male sex or obese, to facilitate early detection and targeted interventions aimed at reducing long-term cardiovascular risk.DiabetesDiabetes type 1Care/Management -
Hospitalizations during the 30-day period preceding admission with pulmonary embolism: insights from the national readmission database.3 weeks agoWe aim to determine the frequency and causes of hospitalizations prior to an admission with a diagnosis of pulmonary embolism (PE).
We conducted a retrospective cohort study using the United States National Readmission Database (NRD) from 2018 to 2020 to evaluate hospitalizations with a primary diagnosis of PE and in-hospital outcomes. We identified the number and causes of hospital admissions occurring within the 30 days preceding the PE hospitalization. Factors associated with prior hospitalization and in-hospital mortality during PE admission were examined. This analysis describes the characteristics of PE patients with prior hospitalization but does not assess risk.
A total of 2,651,870 hospital admissions for PE were included in the analysis, of which 16.3% (n = 431,700) had a prior hospitalization within the preceding 30 days. The most common reason for prior admission was sepsis (10.9%). Other notable but less frequent causes included orthopedic conditions associated with reduced mobility, cancer, and cardiovascular diseases. The strongest predictor of prior hospitalization was elective admission (OR 2.89, 95% CI 2.82-2.95). Additional factors associated with increased odds of prior hospitalization included cancer (OR 1.60, 95% CI 1.57-1.63), prior myocardial infarction (OR 1.24, 95% CI 1.20-1.28), and diabetes mellitus (OR 1.19, 95% CI 1.17-1.21). Prior hospitalization was associated with increased odds of in-hospital mortality during the PE admission (OR 1.95, 95% CI 1.89-2.00).
Approximately one in six patients admitted with PE had a hospitalization in the preceding 30 days, and these patients experienced higher in-hospital mortality. Common reasons for prior admissions included sepsis, orthopedic conditions related to immobility, cancer, and cardiovascular disease.DiabetesCardiovascular diseasesCare/Management