Ji Hu

Background: Elderly patients with type 2 diabetes mellitus (T2DM) often experience cognitive decline and physical function degradation. However, whether cognitive function mediates the association between T2DM and physical performance in older adults has not been previously examined. This study aimed to explore whether cognitive function was statistically associated with the relationship between T2DM and physical performance in older adults using mediation analysis. Methods: We conducted a cross-sectional study, and a total of 102 participants aged ≥60 were included (46 patients with T2DM and 56 non-diabetes controls). Cognition was assessed using standardized neuropsychological tests (global cognition, as assessed by the MoCA total score; and domain-specific measures). Physical performance was quantified by walking speed and handgrip strength. Mediation analyses were performed to test whether the cognitive function statistically accounted for part of the association between the T2DM state and the physical performance. Results: Participants with T2DM had poorer cognitive performance and lower physical performance than controls. In mediation models, the MoCA total score statistically accounted for approximately 18% of the association between T2DM and gait speed (ACME −5.19 cm/s, 95% CI −8.73 to −2.32; proportion mediated 0.18, 95% CI 0.08–0.32). For grip strength, the corresponding proportion was estimated at 60% (ACME −2.16 kg, 95% CI −3.78 to −0.81; proportion mediated 0.60, 95% CI 0.23–1.81), although this estimate should be interpreted cautiously because of the wide confidence interval. Conclusions: This study suggests that poorer cognitive performance may partially account for the observed relationship between T2DM and the decline in physical performance of the elderly. The results support the presence of concurrent cognitive and physical impairment among older adults with T2DM. Given the cross-sectional design, these findings should be regarded as exploratory and hypothesis-generating, and longitudinal studies are required to establish temporal relationships.

Background: Gait impairment is common in older adults with type 2 diabetes mellitus (T2DM). This complication increases risk of falls, disability, and mortality. Although gait disorders are often associated with peripheral deficits, emerging evidence suggests that central mechanisms may play an important role. The relative contributions of central and peripheral factors across gait parameters remain unclear. Methods: In this cross-sectional study, gait parameters were assessed using wearable inertial sensors in 41 older adults with T2DM and 55 age-matched controls. Central factors included medial temporal atrophy (MTA) on magnetic resonance imaging (MRI) and global cognition (MoCA/MMSE). Grip strength was used as the index of peripheral function. Hierarchical regression quantified the incremental variance explained by central versus peripheral factors after adjusting for demographic and vascular confounders. Results: Compared with the control group, the T2DM group showed significantly worse gait performance, including a reduction in gait speed of about 35% ( p < 0.001). For gait speed, central factors (MTA and cognition) explained most of the model’s explained variance, whereas grip strength explained little and was not an independent predictor. Both central and peripheral factors contributed independently to cadence. Conclusion: Hippocampal atrophy and cognitive dysfunction are independently associated with slowed gait speed in the elderly with T2DM. Cadence reflects combined effects of central and peripheral influences. These findings suggest that future intervention research should explore a shift toward from traditional peripherally focused approaches to brain-centered strategies for maintaining motor ability in the future. These findings are cross-sectional and associative; causal inferences require longitudinal validation.

Background Rheumatoid arthritis (RA) has long been observed to co-occur with Hashimoto’s thyroiditis, a condition characterized by the presence of thyroid peroxidase antibody (TPOAb); however, the specific contribution of TPOAb to RA pathogenesis remains unclear. Therefore, we aimed to investigate the association between TPOAb and RA. Methods We performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data from East Asian and European population. This analysis was complemented by functional enrichment analyses and validation using cross-sectional data from 12,014 and 5,270 participants in the National Health and Nutrition Examination Survey (NHANES). Results In East Asian populations, both TPOAb concentration and TPOAb positivity were significantly associated with RA (OR = 1.447, P < 0.001; OR = 1.198, P < 0.001) and seropositive RA (OR = 1.349, P < 0.001; OR = 1.166, P = 0.002). In European populations, TPOAb concentration was significantly associated with RA, seropositive RA, and seronegative RA, while TPOAb positivity was significantly associated with RA and seropositive RA (all P < 0.05), but not seronegative RA. In the NHANES III dataset, TPOAb positivity remained significantly associated with RA and seropositive RA (OR = 1.358, P = 0.045; OR = 1.95, P = 0.046). Functional annotation further revealed enrichment of genes involved in immune regulation, immune cell differentiation, and activation. Conclusion Collectively, these findings provide genetic and observational evidence supporting an association between TPOAb and RA. However, the potential role of TPOAb in rheumatoid arthritis risk prediction requires further investigation. Key Points • TPOAb were associated with rheumatoid arthritis. • The clinical value of TPOAb for rheumatoid arthritis risk prediction requires further validation.

Aims: The purpose of this study was to explore the molecular mechanism of circRNA mediated colonic hypersensitivity in rats with diabetes. Methods: Intraperitoneal injection of streptozocin female rats was used to induce Type 1 Diabetes Mellitus. A combination of molecular biology and behavioral approaches was used to investigate the role of circRbfox1 in the pathogenesis of colonic hypersensitivity in diabetic rats. Results: A new circular RNA‐Rbfox1, derived from the host gene encoding RNA‐Binding Protein Fox1, as a mechanism of visceral pain is identified. We confirmed that circRbfox1 remarkably upregulated in T13‐L2 dorsal root ganglions in rats with diabetes, and could interact with the RNA‐binding protein HuC to promote its transition from the cytosol into the nucleus to promote the translation level of RBFOX1. In addition, the increased expression of Rbfox1 could further promote colonic hypersensitivity in diabetic rats by regulating the expression of Cav1.3. Conclusions: We conclude that circRbfox1 serves as pain regulator in diabetic colonic hypersensitivity and provides a potential therapeutic target in clinic.

Background: Diabetes-related gait disorders are important drivers of falls and functional decline in older adults. Gait variability, as an indicator highly sensitive to fluctuations between steps, remains underexplored in diabetic populations. Compared with the average gait parameters, gait variability may better reflect impaired neuromuscular control and the risk of falling. This study aimed to evaluate the diagnostic accuracy of gait variability parameters, and test whether cognitive function plays an intermediary role between type 2 diabetes mellitus (T2DM) and gait variability. Methods: A total of 56 non-diabetic older participants and 37 T2DM patients (aged 60 years or older) were enrolled in this study. We used wearable inertial sensors to evaluate the gait parameters (including the variability in stance time, gait speed, stride length and turn duration) during straight walking and turning tasks. Standardized tools were used to evaluate cognitive functions, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and other verified measures. Results: Our results showed that T2DM patients exhibited significantly higher gait variability across all indicators. All gait variability indices were significantly negatively correlated with cognitive function (r = −0.20 to −0.53, P < 0.05). After adjusting for demographic characteristics and cognitive functions, the T2DM status was still an independent predictor of gait variability. The receiver operating characteristic (ROC) curve analysis showed that the stance time variability had good diagnostic accuracy (area under the curve [AUC] = 0.813, 95% CI 0.727–0.898, p < 0.001, sensitivity 94.6%), and gait speed variability also demonstrated good diagnostic performance (AUC = 0.801, 95% CI 0.705–0.897, p < 0.001). Mediation analysis showed that cognitive function mediated the effect of T2DM on stance time variability, and the mediated effect accounted for 31.9% of the total effect. Conclusion: This study showed that T2DM patients demonstrated a significant increase in gait variability. This variation was closely associated with cognitive decline. Stance time and gait speed variability could be used as a sensitive and non-invasive screening method to identify gait dysfunction related to diabetes. T2DM may affect gait stability through dual pathways, involving both cognitive decline and non-cognitive mechanisms. Comprehensive intervention strategies (including blood sugar control, neuropathy management and cognitive training) could improve the gait stability of T2DM elderly people and mitigate the risk of falling.

Type 1 diabetes (T1D) is a T cell‑mediated autoimmune disorder characterized by the destruction of insulin‑producing β‑cells. Sialic acid‑binding Ig‑like lectin 15 (Siglec‑15) could inhibit T‑cell activation and suppress immune responses. However, the association between Siglec‑15 expression levels and T1D is largely unknown. Serum concentrations of soluble Siglec‑15 were quantified in a cohort comprising 34 individuals newly diagnosed with T1D and 21 healthy control subjects. A murine mesenchymal stem cell (MSC) line, C3H10 T1/2, was genetically engineered to stably express SIGLEC15 through lentiviral transduction. Non‑obese diabetic (NOD) mice were administered treatments with Siglec15‑expressing MSCs, control MSCs, or phosphate‑buffered saline. The present study evaluated diabetes incidence, blood glucose concentrations, the severity of insulitis and the composition of immune cell populations in the pancreatic lymph nodes and spleens. In the present study, measurement of human serum specimens by ELISA revealed a positive association between new‑onset T1D and soluble Siglec‑15 levels. In NOD mice, treatment with Siglec15‑MSCs resulted in a significant reduction in diabetes incidence, preservation of insulin‑positive islets and mitigation of insulitis. Flow cytometric analysis demonstrated an increase in CD4⁺effector memory T cells within the pancreatic‑draining lymph nodes of mice treated with Siglec15‑MSCs, while no significant alterations were observed in splenic T cell populations or the frequencies of regulatory T cells. The findings of this study underscore the potential of Siglec‑15‑overexpressing MSCs as a promising cell‑based therapeutic approach for T1D, primarily through the localized modulation of memory T cells within the pancreatic lymph nodes.

Aim: The aim of this study was to explore the clinical characteristics and associated factors of constipation in patients with type 2 diabetes (T2DM). Here, we focus on the correlation between time in range (TIR) and coefficient of variation (CV) of glucose and constipation in patients with T2DM. Methods: In the exploratory, cross-sectional study, a total of 120 patients diagnosed with T2DM in the department of Endocrinology and Gastroenterology of Liqun hospital from 2023 to 2024 were recruited. Patients with concurrent constipation were included in the constipation group, and those without concurrent constipation were included in the non-constipation group. Fasting blood indicators of patients were detected, including fasting blood glucose (FBG), 2 hours postgrandial blood glucose (2hPBG), glycosylated hemoglobin type A1C (HbA1c), fasting C-peptide (FCP), homeostasismodel assessment-insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Blood Glucose was monitored by a silicon-based dynamic system for 14 days, and TIR and CV were calculated by a continuous glucose monitoring system (CGM). In addition, the symptoms of constipation, gastroparesis cardinal symptom index (GCSI), patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) and patient assessment of quality-of-life index (PAGI-QOL) were evaluated by questionnaires. The impact of TIR and CV for constipation risk was evaluated using receiver operating characteristic (ROC) curves. Results: 1. More serious condition in constipation symptoms, GCSI, VSI, PAGI-SYM and PAGI-QOL scores in the constipation group. 2. Compared with the non-constipation group, the constipation group had longer courses, and higher probabilites of complications of autonomic neuropathy, diabetic nephropathy and hyperlipidemia; 3. Compared with the non-constipated group, FCP was significantly decreased, and HbA1c, TC and LDL-C were significantly increased in the constipation group. 4. TIR and CV were significantly correlated with constipation in patients with T2DM. Conclusions: Lower TIR and higher CV were associated with constipation in T2DM patients. These findings suggest that CGM-derived metrics may be useful markers of constipation risk and warrant investigation in prospective studies to determine whether improving these parameters can prevent constipation development.

Diabetic encephalopathy (DE), a severe complication of diabetes, is characterized by cognitive decline and neuroinflammation, in which astrocytes play a critical role. YTHDF2, an m⁶A reader protein, has been implicated in regulating inflammatory processes. This study investigated the role of astrocytic YTHDF2 in DE pathogenesis. In a mouse model of high-fat diet-induced DE, we observed significant cognitive impairment and hippocampal inflammation. Astrocyte-specific overexpression of YTHDF2 alleviated these deficits, reducing cognitive dysfunction and the levels of pro-inflammatory cytokines IL-1β and IL-6. Both in vivo and in vitro high-glucose models confirmed that YTHDF2 overexpression suppressed astrocyte activation. YTHDF2 negatively regulated SIGMAR1 expression by promoting SIGMAR1 mRNA degradation, which inhibited astrocyte activation and inflammation. Mechanismly, SRAMP, a sequence-based predictor of m⁶A modification sites, identified four high-confidence m⁶A sites (P828, P916, P938 and P979) in SIGMAR1 mRNA. Mutation of P916 m⁶A site could inhibit SIGMAR1 mRNA degradation induced by YTHDF2 overexpression. Our findings demonstrate that astrocytic YTHDF2 attenuates astrocyte activation and neuroinflammation by promoting SIGMAR1 mRNA degradation in DE progression, which may provide a novel treatment strategy for neuroinflammation and cognitive dysfunction in DE.