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.

Type 1 diabetes mellitus (T1DM) is characterized by autoimmune β-cell destruction and absolute insulin deficiency. While insulin remains the cornerstone of treatment, the adjunctive use of oral hypoglycemic agents (OHAs) has been explored, though clinical evidence in T1DM remains sparse. Mitochondrial dysfunction is increasingly recognized in the pathogenesis and complications of T1DM, and some OHAs are known to modulate mitochondrial pathways, primarily studied in type 2 diabetes mellitus. This review aimed to synthesize existing evidence regarding the roles of OHAs in T1DM, with a specific focus on their potential impact on mitochondrial function. Following PRISMA guidelines, eligible studies investigating mitochondrial dysfunction in T1DM or the effects of OHAs on mitochondrial function in T1DM were included. Of 997 articles screened, 24 studies met inclusion criteria. Twenty studies described the mechanisms of mitochondrial dysfunction in T1DM, highlighting oxidative stress, impaired ATP production, disrupted proteostasis, apoptosis, and altered mitochondrial dynamics. Four preclinical studies suggested that metformin and empagliflozin may improve mitochondrial quality control in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner by enhancing biogenesis and preventing mitochondrial fission in T1DM. Certain OHAs may modulate mitochondrial dysfunction in T1DM, but clinical translation remains speculative and requires further investigation regarding their potential as adjunctive therapy.

Acromegaly is a chronic endocrine disorder caused mainly by GH-secreting pituitary adenomas, leading to excess GH and elevated IGF-1. Although surgery is first-line therapy, many patients require medical treatment, and remission is often not achieved with first-generation somatostatin receptor ligands (SRLs). Pasireotide, a second-generation SRL, offers superior biochemical and tumor control but is associated with hyperglycemia. This study aimed to evaluate real-world outcomes associated with pasireotide treatment in patients with acromegaly inadequately controlled on first-generation SRLs, with IGF-1 normalization as the primary endpoint. Secondary outcomes included GH control, tumor response, and glycemic safety.

We conducted a historical cohort study of adults with acromegaly treated at Clínica Imbanaco (Cali, Colombia) between 2017 and 2024. Eligible patients had residual tumors and persistently elevated GH and/or IGF-1 levels above the age-adjusted upper limit of normal despite treatment with clinically adequate doses of first-generation SRLs, as well as 12 months of continuous pasireotide treatment and follow-up after pasireotide initiation. Demographic, biochemical, imaging, and glycemic data were collected. Statistical analysis included paired and independent Student's t-tests, Wilcoxon signed-rank tests, McNemar's test, and Fisher's exact test, with significance set at p < 0.05.

Fourteen patients (50% female; mean age 52.1 ± 14.5 years) were included. After 12 months, mean IGF-1 decreased from 2.73 ± 0.73 to 0.99 ± 0.56 × ULN, and 50% achieved IGF-1 normalization. Additionally, 35.7% achieved GH < 1 ng/mL, and 14.3% achieved combined control. Mean tumor diameter decreased by -3.26 mm (95% CI -4.56 to -1.95; p < 0.001). HbA1c increased from 5.56% to 6.05%, while type 2 diabetes mellitus prevalence rose from 14.3% to 35.7%. No patient discontinued pasireotide due to metabolic adverse events.

Pasireotide was associated with favorable biochemical and tumor responses in patients with acromegaly inadequately controlled on first-generation SRLs under real-world conditions. Although treatment was associated with higher HbA1c and increased diabetes incidence, proactive monitoring and early management of hyperglycemia may have supported treatment persistence.

The introduction of respiratory multiplex PCR in the post-pandemic world has improved the detection of viral infections, whose clinical relevance is still being characterized. Patients with diabetes mellitus (DM) exhibit altered innate immune responses, yet the effect of concurrent viral infection on their inflammatory trajectory and clinical outcomes remains poorly characterized. This study examined whether diabetes is associated with a more pronounced inflammatory response, delayed resolution, and worse multi-organ outcomes during viral respiratory infections. A prospective, longitudinal cohort of 430 hospitalized adults (DM: n = 211; non-DM: n = 219) with PCR-confirmed viral respiratory infections was stratified into four groups by diabetes and co-infection status using a respiratory multiplex PCR panel. Serum IL-6, CRP, NLR, procalcitonin, and urea were measured at admission (Day 1) and at clinical stabilization (Day 6). All variables failed normality testing (Shapiro-Wilk p < 0.0001); non-parametric methods were applied. Receiver operating characteristic (ROC) analysis was used to identify candidate biomarker cutoffs for mortality prediction. SARS-CoV-2 was the predominant pathogen (29.1%). In an exploratory comparison limited by small subgroup sizes (n = 8 vs. n = 14), co-infected diabetic patients had higher baseline inflammatory markers than co-infected non-diabetic patients: median IL-6 32.87 vs. 6.20 pg/mL (Mann-Whitney p = 0.0006) and median CRP 103.83 vs. 23.03 mg/L (p = 0.0012). At the Day 6 checkpoint, co-infected diabetic survivors had higher IL-6 (12.01 vs. 6.13 pg/mL, p = 0.0183) and showed little within-group NLR change (Wilcoxon p = 0.2367); these Day 6 estimates are subject to survivor selection and should be interpreted accordingly. In-hospital mortality was 25.6% in diabetic vs. 3.7% in non-diabetic patients (p < 0.0001). Diabetic patients more frequently required orotracheal intubation (6.4% vs. 1.0%, p = 0.0207) and high-flow nasal oxygen (HFNO) support (7.9% vs. 1.8%, p = 0.0166). In an internal ROC analysis, baseline IL-6 showed the highest discriminatory performance for in-hospital mortality (AUC 0.812, 95% CI 0.772-0.848), with a candidate cutoff of > 55.78 pg/mL (sensitivity 71.0%, specificity 79.1%); IL-6 outperformed CRP (AUC 0.706, DeLong p = 0.0029) and NLR (AUC 0.656, DeLong p = 0.0001). As this cutoff was derived and evaluated in the same cohort, it is reported as exploratory and requires external validation. In this single-center cohort, diabetes was associated with a more pronounced baseline inflammatory profile, slower resolution of the neutrophil-to-lymphocyte ratio, and greater multi-organ involvement during viral respiratory infection, including in the small co-infected subgroup. In the full cohort, diabetes remained associated with higher mortality, IL-6, and CRP after adjustment for age, sex, and BMI; however, the small co-infected subgroups could not be adjusted, so those specific comparisons should be regarded as hypothesis-generating and need confirmation in larger, adequately powered multi-center cohorts.