Interstitial fibrosis and tubular atrophy (IFTA) is an important pathological feature of diabetic kidney disease (DKD). Its prognostic value in biopsy-proven DKD remains incompletely understood.

In this retrospective study, 164 patients with type 2 diabetes and biopsy-confirmed pure DKD were followed for a median of 38 months. The primary composite kidney endpoint was initiation of kidney replacement therapy or kidney-related death. Predictors were selected using LASSO Cox regression. Random survival forest was used as an exploratory complementary analysis.

Thirty-four patients reached the composite kidney endpoint. After LASSO selection and multivariable adjustment, IFTA score 2/3 (vs. IFTA score 1, HR 3.96, 95%, CI 1.71-9.16, P = 0.001), 24-hour proteinuria (per 1 g/day increase; HR 1.52, 95%, CI 1.19-1.94, P < 0.001), and lower serum calcium (per 1 mmol/L increase; HR 0.140, 95% CI 0.041-0.481, P = 0.002) were independently associated with the composite kidney endpoint. In the random survival forest analysis, serum calcium, baseline eGFR, and IFTA were among the most important variables. Patients with IFTA 2/3 had significantly lower kidney survival than those with IFTA 1 (log-rank P = 0.0056).

In biopsy-proven DKD, IFTA 2/3 was associated with the composite kidney endpoint. Higher 24-hour proteinuria and lower serum calcium were associated with poor kidney outcomes. Further studies are needed to confirm these findings and clarify their clinical implications.

Type 2 diabetes mellitus (T2DM) remains difficult to manage due to progressive β-cell dysfunction and poor glycaemic control, while imeglimin, a novel oral agent with multimodal metabolic effects, has shown promising clinical results but limited real-world evidence, particularly in Indian populations. This study compared short-term glycaemic and metabolic outcomes in adults with T2DM receiving imeglimin versus standard antidiabetic therapy in routine clinical care.

A non-randomized, prospective observational cohort study was conducted among adults with type 2 diabetes mellitus between January and August 2025, comparing imeglimin (n = 88) with standard antidiabetic therapy without imeglimin (n = 100). Clinical and laboratory parameters were assessed at baseline and 3 months, with HbA1c as the primary endpoint. Baseline balance was assessed using standardized mean differences (SMDs). Outcomes were analyzed using multivariable linear regression, ANCOVA, and logistic regression (p < 0.05).

A total of 188 adults with type 2 diabetes mellitus were included (Imeglimin: n = 88; Non-Imeglimin: n = 100), with comparable baseline characteristics. At 12 weeks, the Imeglimin group showed greater reductions in HbA1c, fasting plasma glucose, postprandial glucose, and mean blood glucose (all p ≤ 0.011), and a greater increase in HDL cholesterol (p = 0.003). A higher proportion achieved ≥0.5% HbA1c reduction (52.27% vs 38.00%; adjusted OR: 1.82; 95% CI: 1.01-3.27). In multivariable analysis, imeglimin use was independently associated with lower Week-12 HbA1c (β = -0.29; 95% CI: -0.44 to -0.14; p < 0.001).

Imeglimin use was associated with greater reductions in HbA1c and other glycaemic parameters over 12 weeks compared with non-imeglimin therapy and remained significantly associated with lower Week-12 HbA1c after adjustment for baseline and clinical covariates. Most metabolic parameters remained stable, with a modest improvement in HDL cholesterol observed. Further large-scale studies with longer follow-up are needed to confirm these findings.

Medication adherence is critical for effective blood glucose control and reducing complication risks in patients with Type 2 Diabetes Mellitus (T2DM). However, improving it remains challenging in clinical practice and disease management. This study examined the relationships among social support, empowerment, health literacy, and medication adherence in T2DM patients to explore the multi-path associations underlying medication adherence.

Social support, empowerment, health literacy, and medication adherence constituted the theoretical model. A cross-sectional survey was conducted using convenience sampling at a Grade III Class A hospital in Guiyang City, China. Univariate analyses were performed using nonparametric rank-sum tests. Structural equation modeling (SEM) was applied to test the hypothesized model, and a bootstrap was performed to examine mediation effects.

A total of 261 T2DM patients were included, with a median medication adherence score of 6.75 (IQR 4.50, 7.63), indicating moderate adherence on the MMAS-8. In univariate analysis, educational level showed the strongest association with medication adherence (H = 67.452, p < 0.001). Social support was positively associated with medication adherence through both direct (53.5%) and indirect (46.5%) pathways. The indicators for affectionate support (β = 0.77) and emotional information support (β = 0.72) had the highest standardized factor loadings. Health literacy acted as a significant mediator (effect = 0.256, 95% CI: 0.133-0.460, 31.7%), and a small but significant sequential mediation pathway was observed (effect = 0.062, 95% CI: 0.018-0.147, 7.7%).

In this hospitalized sample of Chinese T2DM patients, empowerment and health literacy sequentially mediated the association between social support and medication adherence. These findings suggest that social support and health literacy may be relevant targets for future intervention research, although longitudinal studies are needed to establish their temporal and causal roles.

Orforglipron (OFG), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RAs), showed potential benefits for type 2 diabetes mellitus (T2DM) and obesity. Its dose-response effects on body weight-related parameters and glycemic outcomes remain incompletely analysed. This network meta-analysis aims to address this gap across multiple doses of OFG (3, 12, 24, 36 and 45 mg) in adults with or without T2DM at 12, 26 and 36 weeks.

PRISMA guidelines were followed in our study. Embase, PubMed, Web of Science and Scopus were searched for randomised controlled trials. Random-effects models expressed OFG effects as odds ratios (OR), mean difference (MD) and standardised mean difference (SMD) with 95% confidence intervals (95% CI). RStudio software (version 4.5.1) was used for analysis.

Six RCTs comprising 4878 participants were included. OFG demonstrated reductions in body weight, BMI and waist circumference across all follow-ups. OFG 45 mg dose produced the greatest effects in body weight (SMD: -1.71 kg at 12 weeks, MD: -8.81 kg at 26 weeks and MD: -12.13 kg at 36 weeks vs. placebo). Categorical weight-loss analyses showed that individuals receiving 24-45 mg increased the odds to achieve ≥ 5%, ≥ 10% and ≥ 15% weight loss at 26 weeks. Glycemic outcomes improved across all doses, with the greatest HbA1c reduction at 45 mg (-1.65%; 95% CI -1.98 to -1.32) and greatest fasting glucose improvement at 36 mg dose. Treatment-emergent adverse events increased with dose.

OFG demonstrated improvements in weight-related outcomes and glycemic outcomes. Adverse events increased with dose, consistent with expected class tolerability.

There is a lack of knowledge on the registration of body mass index (BMI) and prevalence of obesity-related complications in the Belgian healthcare system. We therefore evaluated these in Belgians living with overweight or obesity. BMI registration and obesity-related complication prevalences were determined using cross-sectional data from a Belgian general practitioners' morbidity registry (Intego) with 208 891 personal records and from 3605 visitors to an obesity clinic. Two Intego data subsets were used: 53 555 individuals with and 84 017 individuals without registered BMI. Groups were compared using chi-square tests (p-value of < 0.05). For Intego data, BMI was registered in 25.6% of cases. Individuals with registered BMI (mean BMI 27.1 ± 5.5 kg/m²) had a higher prevalence of hypertension (30.1% vs. 17.0%), dyslipidemia (26.9% vs. 14.7%), prediabetes (17.0% vs. 7.9%), type 2 diabetes (12.7% vs. 4.4%) and sleep apnea (3.8% vs. 1.5%) compared to people without registered BMI. People assessed at the obesity clinic (mean BMI 39.0 ± 6.5 kg/m²) had higher prevalences of hypertension (43.1% vs. 37.5%), dyslipidemia (44.4% vs. 32.9%) and sleep apnea (37.9% vs. 5.5%) compared to Intego individuals with BMI ≥ 25 kg/m²(mean BMI 30.3 ± 4.3 kg/m²). BMI is registered only in 25% of patient files in general practice, and people with a registered BMI in general practice have a substantially higher prevalence of the five obesity-related complications than people without registered BMI. When registered, mean BMI is substantially lower than in the obesity clinic, but the prevalence of complications is already substantial, though lower than in the obesity clinic.

Leptospirosis has been infrequently associated with persistent kidney dysfunction fulfilling the criteria for chronic kidney disease (CKD). However, the entity remains poorly characterised. This study aimed to describe the clinical profile, laboratory findings, treatment requirements, and kidney outcomes of patients without recognised CKD risk factors who had persistent kidney dysfunction fulfilling CKD criteria at three-month follow-up after leptospirosis-associated Acute Kidney Injury (AKI).

This descriptive case series was nested within a prospective cohort of hospitalised patients with leptospirosis admitted to a tertiary care hospital in coastal Karnataka, India, between April 2025 and March 2026. Patients with leptospirosis-associated AKI who fulfilled Kidney Disease: Improving Global Outcomes (KDIGO) criteria for CKD at three-month follow-up were included. Leptospirosis was confirmed by immunoglobulin M (IgM) enzyme-linked immunosorbent assay or polymerase chain reaction (PCR). Patients with known CKD or recognised clinical risk factors for CKD, including diabetes mellitus, hypertension, family history of kidney disease, structural renal abnormalities, or other identifiable causes of kidney disease, were excluded. Clinical features, laboratory parameters, treatment details, organ support requirements, and kidney outcomes were recorded.

Among 101 hospitalised patients with leptospirosis, 67 (66.3%) developed AKI. Of these, 7 (10.4%) died in hospital, and 17 (28.3%) of the 60 survivors did not undergo serum creatinine testing at three-month follow-up. Among the remaining 43 evaluable survivors without known CKD or recognised CKD risk factors, 6 (14.0%) fulfilled criteria for CKD at three-month follow-up. All six patients had KDIGO Stage 3 AKI during admission. Admission serum creatinine ranged from 3.19 to 8.63 mg/dL, while peak serum creatinine ranged from 4.92 to 11.84 mg/dL. Jaundice was present in 4/6, 66.7%, of patients, leukocytosis was observed in all patients, and thrombocytopenia was present in all patients. Pulmonary complications were common, with pleural effusion in 4/6, 66.7%, patients, acute respiratory distress syndrome in 1/6, 16.7%, and diffuse alveolar haemorrhage in 1/6, 16.7%. Myocarditis was noted in 2/6, 33.3%, of patients. Three patients required haemodialysis, and three required mechanical ventilation. At discharge, serum creatinine remained elevated in all six patients, ranging from 1.85 to 5.15 mg/dL. At three-month follow-up, estimated glomerular filtration rate (eGFR) ranged from 44 to 59 mL/min/1.73 m²; five patients were classified as CKD Stage 3a and one as CKD Stage 3b.

Severe leptospirosis-associated AKI may be followed by persistent kidney dysfunction at three months despite improvement in serum creatinine from peak values. Persistent creatinine elevation at discharge may be an important clinical warning sign. Patients with severe leptospiral AKI, particularly those with KDIGO Stage 3 AKI, dialysis requirement, persistent discharge creatinine elevation, or multiorgan involvement, may benefit from structured post-discharge kidney follow-up, including eGFR reassessment, urinalysis, proteinuria assessment, blood pressure monitoring, and, where feasible, tubular function testing.

With the advancement of proteomics technologies, an increasing number of studies have begun to examine semaglutide-associated protein expression changes and pathway alterations across different biological contexts. However, existing evidence remains fragmented across different disease backgrounds, sample types, and research platforms, lacking systematic integration.

This review searched PubMed, Embase, and Web of Science for relevant studies published as of April 2026, including population-based, animal, and in vitro model studies that implemented semaglutide interventions and reported proteomic results.

A total of 16 studies were ultimately included, comprising 4 population-based studies and 12 animal and in vitro model studies. The included studies examined both circulating samples and tissue-level specimens, including serum, plasma, adipose tissue, myocardium, aorta, lung, kidney, hippocampus, and skeletal muscle. Common proteomics platforms utilized included SomaScan, TMT-LC-MS/MS, DIA proteomics, phosphorylation proteomics, and mitochondrial proteomics. Multiple studies identified the PPAR signaling pathway, oxidative phosphorylation, and fatty acid metabolism as frequently occurring pathways, while ECM remodeling, complement/inflammatory pathways, and mTORC1 signaling were also observed in some studies. These results suggest that semaglutide is associated with proteomic changes across metabolic, cardiovascular, hepatic, pulmonary, renal, and nervous systems, with recurring signals involving fatty acid metabolism, mitochondrial function, inflammatory protein networks, and extracellular matrix-related pathways.

Overall, proteomic evidence provides a useful molecular framework for describing semaglutide-associated biological responses across multiple tissues. However, existing studies still have limitations such as small sample sizes, high subject heterogeneity, significant differences in proteomic platforms, and limited population studies. Therefore, future research will require larger sample sizes, standardized designs, and multi-omics integration studies to further determine which proteomic signatures are reproducible, biologically meaningful, and clinically translatable.

Cardiovascular risk factors (RFs) are commonly used in clinical practice to predict future adverse cardiovascular outcomes, including acute coronary syndromes (ACS). A recent study reported an association between RFs and plaque vulnerability in patients with ACS.

This study aimed to investigate the association between RFs (modifiable and non-modifiable) and pan-coronary plaque burden, plaque phenotype, and features of vulnerability.

In patients undergoing 3-vessel optical coherence tomography imaging, modifiable (dyslipidemia, hypertension, diabetes mellitus, obesity, smoking) and non-modifiable (age, sex, family history) RFs were recorded. Plaque number, plaque phenotype, and vulnerable features were analyzed.

A total of 534 plaques from 131 patients (36.6% ACS) were analyzed. As the number of RFs increased, the number of plaques (P trend = 0.001) as well as plaques with a vulnerable phenotype (thin-cap fibroatheromas [TCFAs], P trend = 0.001) increased. An increasing number of RFs was also associated with a higher number of vulnerable features (P trend < 0.001), including more thin fibrous caps (P trend = 0.001), lipid-rich plaques (LRPs), macrophages, microvessels, and cholesterol crystals (all P trend ≤ 0.001). In multivariable analyses, only modifiable RF burden was associated with increased pan-coronary vulnerability (incidence rate ratio [IRR]: 1.36; 95% CI: 1.18-1.57; P < 0.001), including a higher prevalence of TCFAs (IRR: 1.48; 95% CI: 1.20-1.83; P < 0.001), LRPs (IRR: 1.35; 95% CI: 1.15-1.59; P < 0.001), and cholesterol crystals (IRR: 1.50; 95% CI: 1.21-1.87; P < 0.001).

As the number of cardiovascular RFs increased, the number of plaques, plaques with a high-risk phenotype, and vulnerable features also increased. Only increasing modifiable RF burden was associated with greater pan-coronary vulnerability, including more TCFAs and LRPs.

ClinicalTrials.gov NCT01110538.

Lipid-based Nanoparticles (LNPs) have emerged as promising carriers for enhancing the efficacy, safety, and patient adherence of antidiabetic therapies. These systems, including Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), liposomes, and nanoemulsions, exhibit unique physicochemical and pharmacokinetic advantages. Their biocompatibility, ability to protect labile drugs from degradation, and capacity to improve oral bioavailability make them especially valuable for delivering poorly soluble antidiabetic agents. This review comprehensively evaluates various lipid-based platforms, comparing their structural characteristics, drug loading efficiencies, release profiles, and targeting capabilities. SLNs offer excellent stability and controlled release, while NLCs improve drug loading and flexibility. Liposomes provide versatile encapsulation of both hydrophilic and lipophilic drugs, and nanoemulsions are ideal for enhancing rapid absorption. Collectively, these systems outperform conventional formulations by enhancing therapeutic outcomes and reducing systemic side effects. Current challenges, such as large-scale manufacturing and regulatory complexity, are discussed alongside future directions to inform translational research. Lipid-based nanoparticles represent a transformative strategy in the evolution of antidiabetic drug delivery.

Ectopic Cushing syndrome (ECS) is a severe paraneoplastic complication of neuroendocrine neoplasms (NENs), but its association with survival and clinically relevant outcomes remains insufficiently defined in matched real-world cohorts.

To assess the association of code-defined Cushing syndrome compatible with ECS with OS and clinical outcomes in patients with NENs using a large propensity score-matched cohort.

Retrospective cohort study with 1:1 propensity score matching.

Electronic medical records from TriNetX Global Collaborative Network, a federated database aggregating clinical data from international healthcare organizations.

Adult patients (≥18 years) with NEN (n = 105,854), including 265 in the ECS-compatible cohort. After matching, 264 patients in the ECS-compatible cohort were compared with 264 patients without documented Cushing syndrome.

Primary outcome was OS. Secondary outcomes included hospitalization, emergency care use, severe infections, venous thromboembolism, metabolic complications, organ failure, and metastatic progression.

ECS was associated with significantly reduced OS compared with non-ECS patients (8-year survival: 55.3% vs 71.2%; hazard ratio [HR] 1.848 [95% confidence interval 1.348-2.534]; P < 0.001). ECS patients had increased risks of hospitalization, severe infections, venous thromboembolism, and metabolic complications including hypertension, diabetes mellitus, and hypokalemia, as well as organ failure (kidney and liver failure). No significant increase in metastatic progression was observed.

ECS-compatible Cushing syndrome was associated with worse survival and substantially higher morbidity in patients with NENs, mainly reflected by hypercortisolism-related complications rather than tumor progression. Early recognition and treatment of hypercortisolism may be critical to improve outcomes.