Obesity and type 2 diabetes mellitus (T2DM) are multifactorial disorders characterized by insulin resistance, chronic low-grade inflammation, adipose tissue dysfunction, and multi-organ metabolic impairment. MicroRNAs (miRNAs) act as post-transcriptional gene regulators and play critical roles in metabolic homeostasis, the modulation of insulin signaling, adipogenesis, inflammatory pathways, and energy balance in key insulin-target tissues, including liver, skeletal muscle, and adipose tissue. This review summarizes mechanistic and translational insights into miRNA regulation in obesity, insulin resistance, and T2DM, integrating data from human studies and experimental models on miRNA sequence codes and extracellular vesicle sorting pathways. We focus on the tissue-specific and systemic roles of miRNAs, highlighting their contribution to inter-organ communication and metabolic network regulation. In addition, we emphasize their emerging roles as predictive biomarkers, modulators of treatment response, and promising targets for RNA-based interventions. Advances in sequence-specific miRNA sorting and extracellular vesicle-mediated delivery may provide avenues for therapeutic intervention. However, challenges related to delivery efficiency, tissue specificity, off-target effects, and variability in miRNA quantification remain important barriers to clinical translation. Addressing these limitations may help define the clinical utility of miRNAs as biomarkers and therapeutic targets in metabolic disorders.

Type 2 diabetes (T2D) is often accompanied by chronic low-grade inflammation, with altered cytokine balance. Although cytokine profiles have often been compared between patients with T2D and healthy individuals, less is known about how they differ among patients with varying disease duration. The aim of this exploratory study was to compare selected pro-inflammatory and anti-inflammatory cytokines in patients with shorter and longer duration of clinically diagnosed T2D. Anonymized surplus serum samples from 18 patients with T2D were analyzed. Patients were divided into two groups according to disease duration: 1-7 years and 8-16 years post-T2D diagnosis. Serum concentrations of six pro-inflammatory cytokines (IL-1β, IL-5, IL-6, IL-8, TNF-α and IFN-γ), three cytokines with anti-inflammatory or immunoregulatory functions (IL-2, IL-4, IL-10), and pro- and anti-inflammatory ratios were measured. All tests were performed using MAGLUMI X8 (Snibe Diagnostics, Shenzhen, China) high-sensitivity chemiluminescent immunoassay according to the manufacturer's guidelines. Statistical analysis of the data obtained was performed using GraphPad Prism (Boston, MA, USA). The longer-duration T2D group showed higher median concentrations of several pro-inflammatory cytokines, particularly IL-6, IL-8, TNF-α, and IFN-γ, compared with the shorter-duration group. Several values in the longer-duration group exceeded the assay-specific reference intervals provided by the diagnostic platform. Anti-inflammatory and immunoregulatory cytokines showed less consistent differences between groups. Correlation analysis indicated stronger correlations among pro-inflammatory cytokines than among anti-inflammatory or immunoregulatory cytokines. This cross-sectional study suggests that cytokine profiles may differ between patients with shorter and longer durations of T2D, with a pattern consistent with a more pro-inflammatory profile in the longer-duration group. Because of the small sample size, absence of healthy controls, and limited availability of clinical covariates, these findings should be interpreted as descriptive rather than confirmatory and require validation in larger, longitudinal studies with detailed metabolic characterization.

Background/Objectives: Lower gastrointestinal bleeding (LGIB) is a common and potentially life-threatening emergency that disproportionately affects elderly, comorbid patients, yet evidence-based risk stratification tools remain underused. The Oakland Score was developed to identify patients who can be safely discharged. This study aimed to determine prognostic factors in patients presenting with LGIB and to evaluate the relationship between the Oakland Score and adverse clinical outcomes. Methods: In this single-centre, retrospective, descriptive study, patients aged 18 years and older who presented to the emergency department with LGIB between 2015 and 2024, and who were evaluated, treated and followed up by the Department of Gastroenterology at Dokuz Eylül University, and who underwent endoscopic evaluation were reviewed. A total of 890 patients who met the inclusion criteria and had complete medical records, defined as full availability of all Oakland Score variables and primary outcome data, were included in the final analysis. The Oakland Score was calculated for every patient, and its association with mortality, intensive care unit (ICU) admission, blood-product transfusion, early and late rebleeding, and the need for emergency surgery was analysed. Receiver operating characteristic (ROC) analysis was used to assess discriminative performance. Results: The mean age was 69.8 ± 15.6 years, and 50.4% of patients were female. The most frequent comorbidities were hypertension (56.2%), coronary artery disease (28.9%) and diabetes mellitus (25.1%). Diverticular bleeding was the most common aetiology (25.1%). Red blood cell transfusion was required in 52.8% of patients, and the in-hospital mortality rate was 6.1%. The Oakland Score was significantly associated with mortality, ICU admission, blood-product transfusion, early and late rebleeding, and emergency surgery (all p < 0.05). On ROC analysis the score performed best for ICU admission (AUC 0.754) and mortality (AUC 0.706), and was significantly associated with red blood cell, platelet and fresh frozen plasma transfusion requirements (p < 0.001). On multivariable logistic regression, the Oakland Score was an independent predictor of one-month rebleeding (OR 1.082; 95% CI 1.032-1.133; p = 0.001) but did not retain independent significance for mortality or ICU admission after adjustment for malignancy, serum albumin and BUN. Conclusions: The Oakland Score is significantly associated with major adverse outcomes in LGIB and is particularly sensitive for predicting mortality and ICU admission. It is a useful adjunct to clinical judgement for risk stratification, although it should be interpreted alongside the patient's overall clinical status.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), represents a major global health challenge, driven by the increasing prevalence of obesity and sedentary lifestyles. T2DM is characterized by insulin resistance and progressive β-cell dysfunction, leading to chronic hyperglycemia and multiple complications. Among the molecular targets investigated for therapeutic intervention, protein tyrosine phosphatase 1B (PTP1B) has emerged as a key negative regulator of insulin signaling. By dephosphorylating the insulin receptor and its downstream substrates, PTP1B attenuates insulin action and contributes to metabolic dysfunction. In addition to its role in glucose homeostasis, PTP1B is implicated in obesity, diabetic complications, neurodegenerative disorders, and cancer, highlighting its relevance as a multifunctional therapeutic target. However, the development of PTP1B inhibitors remains challenging due to the highly conserved and polar nature of its catalytic site, which limits selectivity and cell permeability. Recent research has focused on alternative strategies, including allosteric modulation and multi-site inhibition, to overcome these limitations. This review provides a comprehensive overview of PTP1B inhibitors from both synthetic (2019-2025) and natural sources, with particular emphasis on natural products reported from 2022 onwards, while including selected earlier studies to provide historical context and illustrate representative structural classes and inhibition mechanisms. Although PTP1B remains an attractive therapeutic target, its clinical validation for diabetes treatment has yet to be achieved. Continued advances in medicinal chemistry and allosteric modulation may help overcome the current translational barriers.

This study aimed to evaluate the long-term effects of lobeglitazone on renal function, glycemic control, metabolic parameters, and safety in Korean patients with type 2 diabetes mellitus (T2DM) treated for over 1 year.

This retrospective, non-interventional, multicenter observational study was conducted at 30 institutions in South Korea. Patients with T2DM who had received lobeglitazone for at least 1 year and had available estimated glomerular filtration rate (eGFR) data were included. Primary outcomes were changes in eGFR and urinary albumin-creatinine ratio (UACR). Secondary outcomes included changes in HbA1c, body weight, lipid profiles, insulin resistance, β-cell function, and adverse events (AEs).

Of the 2743 enrolled patients, 2648 and 2500 were analyzed for safety and efficacy, respectively. Of 2648 patients analyzed for safety, 1655 (62.5%) were male and 993 (37.5%) were female. Baseline eGFR (82.0 ± 22.0 ml/min/1.73 m²) remained stable over 6 years across all chronic kidney disease (CKD) stages. UACR was unchanged in 77-83% of patients throughout follow-up. HbA1c significantly decreased from baseline (- 0.99% at year 1 to - 0.93% at year 6; all p < 0.0001), indicating sustained glycemic control. Lipid profiles and HOMA-IR improved, while HOMA- β remained stable. Overall, 1165 AEs occurred in 531 patients (20.05%), mostly consistent with the established safety profile; events of special interest were rare (< 1%).

Long-term lobeglitazone treatment was not associated with deterioration of renal function or worsening of albuminuria status across all CKD stages, while demonstrating sustained glycemic efficacy and a favorable safety profile in real-world clinical practice. These findings support lobeglitazone as a clinically relevant long-term treatment option for patients with T2DM, including those with pre-existing CKD.

Type 1 diabetes begins as an autoimmune disease and can already be diagnosed in the presymptomatic early stage by detecting at least two positive islet autoantibodies (stage 1, International Classification of Diseases, 10th Revision, German Modification [ICD-10-GM]: R76.80; stage 2, ICD-10-GM: R73.00). Immunomodulatory therapies can slow disease progression and delay the clinical manifestation of type 1 diabetes. In parallel, cell therapy for β‑cell replacement is gaining increasing importance as a strategy to restore endogenous insulin production.

This article provides an overview of the current status of immunotherapies and cell therapies in type 1 diabetes.

The review "The future of type 1 diabetes therapy" by Ziegler et al. (2025) served as the basis. In addition, current guidelines, original articles, and selected studies on immunotherapies and β‑cell replacement therapies were considered.

With teplizumab, the first disease-modifying therapy for stage 2 type 1 diabetes is available. It delays the transition to clinically manifest type 1 diabetes (stage 3) by an average of 2-3 years. Other immunomodulatory therapeutic approaches show preservation of residual β‑cell function in stage 3 type 1 diabetes but are not yet approved for this indication. Stem-cell-based β‑cell replacement therapies are currently being clinically investigated in people with advanced diabetes and impaired awareness of hypoglycemia.

Immunotherapies and cell therapies mark a paradigm shift in the treatment of type 1 diabetes. In the future, combination therapies will be particularly important to improve the durability of therapeutic effects, as will strategies to protect transplanted cells from alloimmunity and autoimmunity.

In Germany, 9.3 million people are affected by type 2 diabetes mellitus [27, 29]. Diabetic foot syndrome encompasses the structural and functional damage to the foot that occurs as a result of this underlying condition and can progress to Charcot foot in advanced stages. This complex clinical condition requires specialized, experienced treatment, with the preservation of the limb and its function as the primary therapeutic goal. Conventional open surgical procedures have so far been only moderately successful due to high complication rates. In contrast, minimally invasive surgery (MIS) offers significant advantages, particularly for patients with increased peri- and postoperative risk. Through precise correction of deformities using minimally invasive surgery (MIS) and the appropriate selection of internal and/or external osteosynthesis techniques based on the specific indication, favorable postoperative outcomes can be achieved and the amputation rate reduced.

Background Patients with diabetes mellitus (DM) are at increased risk of adverse cardiovascular outcomes. Current risk scores for DM rely solely on clinical risk factors and ignore parameters that directly reflect cardiac structure and function such as imaging biomarkers. Purpose To develop a cardiac MRI-based predictive model for cardiovascular outcomes among participants with type 2 DM and evaluate the model in comparison with established clinical risk models. Materials and Methods This study prospectively and retrospectively enrolled participants with DM who underwent cardiac MRI between January 2016 and December 2023, comprising a training set, internal test set, and external test set, in which the risk model was developed and evaluated. The primary outcome was heart failure hospitalization or cardiovascular death. Multivariable Cox regression analysis was performed to develop the risk model. Results Among 1388 participants with DM (mean age, 57 years ± 12.3 [SD]; 955 men), 145 of 810 participants in the training set experienced the primary outcome during a median follow-up of 37.6 months (IQR, 26.5-58.6 months). The MRI-based risk model demonstrated good discrimination (C index, 0.73) and acceptable calibration. On the basis of eight identified risk predictors, an integer-based SCAN-MRI (sex, coronary artery disease, age, atrial fibrillation, N-terminal pro-B-type natriuretic peptide, and MRI variables) risk score was created to predict 3-year outcome incidence. Compared with established WATCH-DM (weight [body mass index], age, hypertension, creatinine, high-density lipoprotein cholesterol, diabetes control [fasting plasma glucose], electrocardiography QRS duration, myocardial infarction, and coronary artery bypass grafting; area under the receiver operating characteristic curve [AUC], 0.66) and Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes risk models (AUC, 0.65), the SCAN-MRI risk model showed better predictive performance (AUC, 0.76; both P < .001). Adding cardiac MRI markers into these risk models improved the discriminative ability to predict adverse outcomes (AUC, WATCH-DM: 0.66 to 0.74 [P < .001]; Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes: 0.65 to 0.73 [P < .001]). In the external test set, the risk model showed good performance in predicting adverse outcomes (C index, 0.71). Conclusion A cardiac MRI-based multivariable risk model, integrating clinical factors and MRI parameters, demonstrated good discrimination and better performance than current established risk models in predicting adverse outcomes in participants with DM. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Varga-Szemes and Emrich in this issue.

Prolonged hyperglycemia, increasing beta-cell loss, and therapeutic inertia are common outcomes of the conventional stepwise approach to treating newly diagnosed type 2 diabetes mellitus (T2DM). In order to quickly achieve glycemic objectives and alter the course of the disease, recent guidelines recommend early combination therapy. However, putting this paradigm into practice necessitates careful assessment of diverse pharmacological profiles. The goal of this review is to assess the available data on early combination therapy for newly diagnosed T2DM, with an emphasis on safety profiles, clinical efficacy, and patient care strategies.

Recent clinical trials (RCTs), meta-analyses, and significant international guidelines evaluating initial triple therapy against sequential monotherapy were identified by searching online databases such as Web of Science, PubMed, and Scopus. Medical Subject Headings (MeSH) terms such as "triple combination therapy," "newly diagnosed diabetes mellitus," "T2DM," and "cost-effectiveness" were included in the search strategy. RCTs, real-world observational studies, and health-economic evaluations were all included in the review.

In terms of achieving and sustaining HbA1c objectives, promoting weight loss, and preserving beta-cell activity, early combination therapy shows higher efficacy. Additionally, compared with earlier secretagogue-based regimens, contemporary combinations have superior safety profiles, reducing the incidence of hypoglycemia and adverse effects. Importantly, the choice of agents needs to be customized. The optimal therapy combination is determined by patient- specific factors, such as the presence of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), baseline HbA1c, weight management objectives, and socioeconomic factors.

A proactive transition from sequential add-on therapy to initial combination regimens is necessary to optimize the management of newly diagnosed T2DM. Clinicians can optimize cardiometabolic benefits, guarantee long-term safety, and enhance overall quality of life by using a patient-centered, customized approach.

Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) frequently present to emergency departments (EDs) with acute metabolic or renal complications. Nutritional risk may coexist with disease severity in this population, but its relationship with hospital admission remains insufficiently characterized. This study aimed to compare the nutritional status between admitted and discharged ED patients with DM and/or CKD.

This single-center prospective observational comparative study included 101 adult ED patients with documented DM and/or CKD. Nutritional status was assessed during the ED encounter using the Nutritional Risk Screening-2002 (NRS-2002) and Mini Nutritional Assessment (MNA). Clinical, anthropometric, and laboratory variables were compared between admitted and discharged patients. Logistic regression was used to explore factors associated with hospital admission.

Of 101 patients, 51 were admitted, and 50 were discharged. NRS-2002-defined nutritional risk was more frequent among admitted than discharged patients (64.7% vs. 30.0%; risk difference: 34.7 percentage points, 95% CI: 16.4-53.0; p = 0.001). MNA-defined malnutrition was also more frequent among admitted patients (45.1% vs. 12.0%; risk difference for malnutrition alone: 33.1 percentage points, 95% CI: 16.7-49.5), and the overall MNA category distribution differed significantly between groups (p < 0.001). Admitted patients had higher C-reactive protein and urea concentrations and lower lymphocyte counts (p = 0.001 for all), while creatinine showed a borderline between-group difference (p = 0.049). In the exploratory adjusted model, hospital admission was associated with serum urea (OR: 1.018, 95% CI: 1.007-1.029; p = 0.001), CRP (OR: 1.022, 95% CI: 1.008-1.036; p = 0.002), female sex (OR: 0.307, 95% CI: 0.098-0.965; p = 0.043), and MNA-defined malnutrition compared with normal nutritional status (OR: 7.926, 95% CI: 1.482-42.391; p = 0.016), although estimates were limited by the number of admission events.

Among ED patients with DM and/or CKD, nutritional risk was substantially more common in those requiring hospital admission. This association likely reflects confounding by indication and possible reverse causation, as disposition decisions may incorporate frailty, general appearance, functional decline, and clinical vulnerability, which are also partly captured by nutritional screening tools. Nutritional screening should therefore be interpreted as a marker of clinical vulnerability rather than as an isolated determinant of disposition.