To characterize metabolic and transcriptional alterations in diabetic kidney disease (DKD) and identify diagnostic biomarkers using a multi-omics approach. Mendelian randomization (MR) was used to assess causal relationships between metabolites and DKD. Renal transcriptomic datasets validated pathway and gene alterations. Machine learning models evaluated diagnostic performance, with SHAP for interpretation. Single-cell and spatial transcriptomics defined cell-specific expression patterns. In silico gene perturbation and in vitro validation in high-glucose–treated HK-2 cells were conducted. MR analysis identified 60 plasma metabolites whose genetically predicted levels showed evidence of association with DKD. These metabolites were enriched in one-carbon metabolism, histidine metabolism, and glycine, serine, and threonine metabolism, which showed consistent alterations in renal transcriptomic analyses. Machine learning models showed strong diagnostic performance (mean AUC = 0.963), with MAOA, CTH, and ALDH1L1 as key contributors. CTH was specifically expressed in proximal tubular cells and downregulated in injury-associated subpopulations. Functional analyses indicated that CTH affected epithelial integrity, mitochondrial metabolism, and immune responses, and was suppressed under high-glucose conditions. These findings provide insight into DKD pathogenesis and highlight CTH as a potential biomarker and therapeutic target.
To examine whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is associated with contrast-associated acute kidney injury (CA-AKI) after contrast-enhanced computed tomography (CE-CT) or computed tomographic angiography (CTA) in adults with type 2 diabetes and chronic kidney disease (CKD). We conducted a TriNetX retrospective cohort study of adults with type 2 diabetes and CKD who underwent CE-CT or CTA from January 2020 to January 2025. GLP-1 RA use was defined by a prescription within six months before imaging. The primary outcome was a new acute kidney injury diagnosis within three days. Separate 1:1 propensity score-matched analyses were conducted for CE-CT and CTA, with eGFR-stratified and sensitivity analyses. After matching, the CE-CT and CTA cohorts included 6,995 and 3,285 pairs, respectively. CA-AKI occurred in 3.8
Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with adverse maternal and neonatal outcomes. Nationwide real-world data describing characteristics , screening practices, clinical management, and quality of care of women with GDM attending diabetes clinics in Italy are limited. We conducted a retrospective observational study using data from the AMD Annals Initiative, a well-established large quality-of-care monitoring program. Anonymized clinical data from women with GDM attending participating centers during 2025 were analyzed. Study measures included demographic characteristics, risk factors, oral glucose tolerance test (OGTT) timing and results, therapeutic management, intermediate outcomes, and available maternal and neonatal outcomes.The analysis was descriptive. A total of 13,487 women with GDM were included. The mean age was 33.6±5.4 years, and 41.1
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for patients with type 2 diabetes (T2D) and obesity. However, their safety in patients with prior pancreatitis remains uncertain. This systematic review aims to evaluate the risk of recurrent acute pancreatitis (RAP) associated with GLP-1 RA therapy. We systematically searched for studies evaluating the safety of GLP-1 receptor agonists in adults with type 2 diabetes mellitus (T2DM) or obesity and a history of acute pancreatitis. The primary outcome was recurrent acute pancreatitis. We included studies of adults with prior acute pancreatitis treated with GLP-1 receptor agonists for type 2 diabetes, obesity, or related metabolic conditions. Studies without recurrent acute pancreatitis outcomes, pediatric populations, overlapping cohorts, insufficient data, or non-original publications were excluded. We included four studies comprising 10,624 patients, of whom 5,427 (51.0
This study aims to explore the effect of miR-142-3p on the endocytosis in human liver sinusoidal endothelial cells (HLSECs) induced by high glucose and to investigate the underlying mechanisms. Multi-database target prediction was performed to identify potential targets of hsa-miR-142-3p. HLSECs were cultured under 5.5 mmol/L glucose (normal) or 25 mmol/L glucose (high) conditions. qRT-PCR assessed the RNA expression levels of miR-142-3p and CLTA. Western blot assessed the protein expression levels of clathrin-mediated endocytosis(CME)-related genes. Immunofluorescence assay was used to observe the cellular localization of CLTA. A dual-luciferase assay investigated the targeting relationship between miR-142-3p and CLTA. DiI-LDL endocytosis assay was used to study the endocytosis in HLSECs. Bioinformatics analysis predicted CLTA as a potential target of miR-142-3p. The expression level of miR-142-3p was increased and the expression levels of CLTA, α-adaptin, AP2M1 and VPS35 were reduced in high glucose-induced HLSECs (P < 0.05). DiI-LDL endocytosis assay demonstrated that the endocytosis was weakend in HLSECs induced by high glucose. Dual-luciferase reporter assay confirmed that miR-142-3p directly targets CLTA. Compared with the negative control group, inhibition of miR-142-3p significantly increased the expression levels of CLTA, AP2M1, α-adaptin and VPS35, and improved the endocytosis in HLSECs (P < 0.05). In contrast, overexpression of miR-142-3p showed the opposite effects. miR-142-3p overexpression targets CLTA and impairs CME in HLSECs induced by high glucose. The concurrent changes in other CME-related genes further suggest a broader regulatory role of miR-142-3p on the endocytosis.
