Bon Jeong Ku

Background and Objectives: Sodium–glucose cotransporter-2 (SGLT2) inhibitors provide cardio-renal protection in type 2 diabetes, but tolerability-related discontinuation is common, creating a need for effective replacement therapy. Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as follow-on agents, yet the clinical course after such a switch has not been systematically characterized, and whether individual DPP-4 inhibitors differ in efficacy in this setting is unknown. Materials and Methods: We conducted a single-center retrospective cohort study at Chungnam National University Hospital (Daejeon, Republic of Korea) between January 2013 and January 2025, including 117 adults with type 2 diabetes who switched from an SGLT2 inhibitor to a DPP-4 inhibitor and met pre-specified criteria for medication stability and follow-up. The primary outcome was the change in glycated hemoglobin (HbA1c) from baseline to 3 months; secondary outcomes were changes in body weight, body mass index, blood pressure, and renal parameters. A pre-specified subgroup analysis compared teneligliptin (n = 60) with other DPP-4 inhibitors as a class (n = 57). Results: In the overall cohort, body weight rose by 0.7 kg and systolic blood pressure by 4.3 mmHg at 3 months (both p < 0.05), whereas HbA1c was unchanged (p = 0.157). In the subgroup analysis, HbA1c fell significantly with teneligliptin (−0.36%; 95% confidence interval, −0.62 to −0.10; p = 0.009) but not with other DPP-4 inhibitors (+0.13%). The between-group difference was −0.49% (95% confidence interval, −0.83 to −0.15; p = 0.005) and persisted after adjustment for baseline HbA1c and estimated glomerular filtration rate (p = 0.007). Conclusions: Switching preserved overall glycemic control at 3 months but produced modest, anticipated increases in body weight and blood pressure. Teneligliptin was associated with a greater HbA1c reduction than the pooled group of other DPP-4 inhibitors; this association persisted after adjustment for the two available baseline covariates but could not be adjusted for diabetes duration, medication adherence, diabetic complications, or other unmeasured factors. Because confounding by indication and other residual confounding cannot be excluded in this short-term, single-center analysis, this finding is hypothesis-generating only and requires confirmation in adequately powered prospective head-to-head trials. Importantly, this study evaluated only the glucose-lowering effect of the switch; because the cardio-renal protection of SGLT2 inhibition is not reproduced by DPP-4 inhibitors, a DPP-4 inhibitor should be regarded as an unavoidable substitute when an SGLT2 inhibitor cannot be maintained rather than a therapeutically equivalent replacement, and preserved HbA1c at 3 months does not establish clinical equivalence between the two strategies.

Introduction: Dyslipidemia accompanied by metabolic syndrome substantially elevates cardiovascular risk by clustering multiple risk factors, including abdominal obesity, hypertension, hyperglycemia, and atherogenic dyslipidemia. The prevalence of both conditions is rising in Korea, underscoring the need for effective and metabolically safe lipid-lowering therapy. LivaloZet ^® Tablet (pitavastatin/ezetimibe fixed-dose combination) addresses this need by combining complementary cholesterol-lowering mechanisms with the glucose-neutral profile of pitavastatin. Methods and analysis: The PIVOT study is a multi-center, non-interventional, prospective observational study enrolling up to 10,000 Korean adult patients with dyslipidemia accompanied by metabolic syndrome who have been prescribed LivaloZet ^® Tablets (pitavastatin/ezetimibe 2/10 mg or 4/10 mg) by their treating physician as part of routine clinical care. Metabolic syndrome is defined according to the modified NCEP-ATP III criteria for the Asian population. Assessments are conducted at baseline, Week 24, and Week 48. The primary endpoint is the percent change in low-density lipoprotein cholesterol (LDL-C) from baseline at Week 24. Secondary endpoints include LDL-C changes at Week 48, changes in the full lipid panel, and LDL-C target achievement rates by cardiovascular risk group. Exploratory endpoints encompass glucose metabolism parameters (HbA1c, HOMA-IR, HOMA-β), medication adherence and persistence, and high-sensitivity C-reactive protein. Safety is assessed through adverse events, laboratory tests, and vital signs, including systematic monitoring of AST, ALT, and creatine kinase for statin-related hepatotoxicity and myopathy. The study was approved by the Institutional Review Board of Chungnam National University Hospital (2025-07-065) and is registered at ClinicalTrials.gov (NCT07523971). Discussion: The PIVOT study will generate prospective large-scale real-world evidence on the LDL-C-lowering effectiveness and safety patterns associated with use of a pitavastatin/ezetimibe fixed-dose combination in Korean patients with dyslipidemia accompanied by metabolic syndrome. The inclusion of glucose metabolism and inflammatory markers will provide descriptive information on the metabolic safety profile of this regimen. As a non-randomized, single-arm observational study, this design cannot establish causal effects or comparative efficacy versus other lipid-lowering regimens. Findings should be interpreted descriptively, acknowledging potential confounding by indication, selection bias, and inter-laboratory variability.

Gestational diabetes mellitus (GDM) is associated with placental dysfunction, which contributes to adverse pregnancy outcomes. This study aimed to compare transcriptomic profiles and immune signatures in placentas from pregnancies with and without GDM. Placental tissues from 22 participants (12 GDM and 10 controls) were analyzed using ribonucleic acid sequencing. Differentially expressed genes were identified and subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. X-cell analysis was used to assess immune cell composition. Western blotting validated the expression of selected genes. A total of 1045 differentially expressed genes were identified. Among these, COL22A1 , COL8A2 , ACTC1 , PAX6 , PPP2R2C , G6PC were significantly upregulated. In contrast, LEP and ERBB2 were downregulated in GDM placentas. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that extracellular matrix organization, muscle contraction, and calcium signaling pathways were upregulated. Pathways involved in glucose import, amino acid transport, and the endoplasmic reticulum (ER) stress response were downregulated. X-cell analysis suggested alterations in stromal and immune cell composition, with increased myocytes and fibroblasts and reduced M2 macrophages in GDM placentas. We found that various molecular signatures, including composition, metabolism, ER stress, and immune cells, were altered in GDM placentas compared to controls. This study demonstrates that the GDM placentas exhibit significant transcriptomic alterations, including changes in metabolic, ER stress-related, and immune pathways. These findings highlight the role of placental remodeling in the pathophysiology of GDM and may provide insights for future research and potential therapeutic strategies.

Diabetic microvascular complications, including nephropathy, retinopathy, and neuropathy, are major causes of morbidity in diabetes. Increasing evidence highlights neutrophils as key contributors to the chronic inflammatory processes underlying these complications. In the diabetic environment, neutrophils exhibit impaired recruitment, defective phagocytosis, dysregulated degranulation, and excessive production of reactive oxygen species and neutrophil extracellular traps (NETs). These dysfunctions not only reduce pathogen clearance but also exacerbate tissue injury through persistent low-grade inflammation. Furthermore, neutrophils interact with other immune cells, such as macrophages, dendritic cells, T cells, and B cells, perpetuating immune imbalance and tissue damage. Various neutrophil-derived cytokines and granular proteins also influence vascular permeability and endothelial dysfunction. In recent years, neutrophil-related biomarkers—such as absolute neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-neutrophil ratio, and systemic immune-inflammation index—have gained attention as accessible and cost-effective tools for predicting and monitoring diabetic microvascular complications. This review summarizes the multifaceted roles of neutrophils in the pathogenesis of diabetic microvascular disease and highlights emerging clinical applications of neutrophil-based inflammatory biomarkers. A better understanding of neutrophil-driven mechanisms may open new avenues for early diagnosis, therapeutic intervention, and personalized care in diabetic patients.

Osteoarthritis (OA), characterised by cartilage destruction, is the most common degenerative joint disease. However, no effective disease-modifying OA therapy is currently available. Herein, we report orphan nuclear receptor small heterodimer partner (SHP, NR0B2) as a novel catabolic regulator of OA pathogenesis. NR0B2 expression was markedly downregulated in cartilage from patients with OA. Global or chondrocyte-specific Nr0b2 deletion in male mice exacerbated OA-related pain and structural changes following surgical destabilization of the medial meniscus, accompanied by increased matrix metalloproteinase (MMP)-3 and MMP-13 expression in chondrocytes. Conversely, adeno-associated virus-mediated Nr0b2 overexpression in knee joints of male mice protected against accelerated knee OA caused by Nr0b2 deficiency. Mechanistically, NR0B2 inhibited IKKβ kinase activity via IKK complex interaction, downregulating NF-κB signalling. Our results demonstrate that NR0B2 has a chondroprotective role in OA progression by regulating matrix-degrading enzymes in an IKKβ/NF-κB-dependent manner, and gene therapy targeting Nr0b2 may be a promising therapeutic strategy for OA.

Background: Insulin resistance is a hallmark of type 2 diabetes mellitus (T2DM) and is associated with metabolic disorders. Adipose tissue plays a crucial role in regulating whole-body energy balance and glucose homeostasis. Mitogen-inducible gene 6 (Mig-6) is a negative feedback regulator of receptor tyrosine kinases, including epidermal growth factor receptor (EGFR). This study aims to evaluate the role of Mig-6 in white adipose tissue (WAT) and its impact on systemic glucose homeostasis using Mig-6 transgenic mice. Methods: Human visceral fat samples were obtained from four obese and three lean women undergoing hysterectomy. Adipocyte-specific Mig-6 knock-in (Mig-6^AdKI) mice were generated and maintained on either a high-fat diet (HFD) or normal chow diet (NCD). Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed. We conducted histological examinations to observe tissue morphology and used quantitative PCR to assess adipokine mRNA expression. Results: Mig-6 expression was significantly reduced in the adipose tissue of obese mice and humans. Mig-6^AdKI mice exhibited improved glucose tolerance and insulin sensitivity under both NCD and HFD conditions, without changes in body weight or fat mass. The improvement in glucose homeostasis under NCD conditions was particularly noteworthy. Increased adiponectin mRNA levels were observed in the WAT of Mig-6^AdKI mice. Meanwhile, histological analysis did not observe any changes in adipose tissue morphology that could explain the improvement in systemic glucose homeostasis, although there were tendencies towards increased adipocyte size and inflammation in HFD-fed Mig-6^AdKI mice. Conclusion: Adipose-specific overexpression of Mig-6 improves systemic glucose tolerance and insulin sensitivity, suggesting its potential as a target for both the treatment and prevention of diabetes. These findings provide a reference for further research targeting EGFR or Mig-6 in adipose tissue, highlighting the metabolic role of Mig-6 in glucose homeostasis.

Background: Uteroglobin is a multifunctional protein with anti-inflammatory properties. Studies have revealed the importance of inflammation in type 2 diabetes mellitus (T2D) pathogenesis. Here, we investigated the relationship between uteroglobin and T2D.Methods: We performed diagnostic tests for diabetes in subjects who had not been diagnosed with or treated for T2D. We established three groups, containing those with normal glucose tolerance (NGT), prediabetes and T2D, consisting of 80 people each, and compared their uteroglobin levels. In addition, 28 patients newly diagnosed with T2D were treated with metformin for 12 weeks, and 63 patients newly diagnosed with dyslipidaemia during the treatment for T2D were treated with statin for 12 weeks.Results: This study showed that uteroglobin levels were significantly lower in prediabetes and T2D groups than in the NGT group. Uteroglobin levels were not significantly correlated with other metabolic parameters, except BMI, HOMA-β and eGFR. In the group treated with metformin or statin, uteroglobin levels increased after treatment compared to before treatment.Conclusions: Uteroglobin is a sensitive factor that was decreased even in prediabetes and increased upon treatment with drugs with anti-inflammatory effects. Uteroglobin is a potential early biomarker that reflects a chronic inflammatory condition in T2D.