This letter builds on a recent study by Fan et al , demonstrating that electroacupuncture (EA) at the Zusanli acupoint can alleviate diabetic gastroparesis by suppressing macrophage pyroptosis via cyclic GMP-AMP synthase-stimulator of interferon genes pathway inhibition. While the authors convincingly demonstrated an immune-inflammatory mechanism underlying the therapeutic effects of EA, we argue that the most important implication of this work lies in how stimulation frequency may encode biologically distinct neuromodulatory information. In this view, EA is not merely a nonspecific peripheral intervention. We propose a hypothesis-driven, non-exclusive framework in which high-frequency EA preferentially engages afferent sensory fibers and autonomic neural circuits, thereby reshaping gastric immune tone and inflammatory thresholds in the diabetic state. Local tissue activation and vascular or perfusion-related dynamics may also operate in parallel. From this perspective, attenuation of macrophage pyroptosis and downstream cyclic GMP-AMP synthase-stimulator of interferon genes signaling can be viewed as secondary consequences of broader neuroimmune and immunometabolic reprogramming initiated by frequency-dependent neural inputs. Recognizing stimulation frequency as an informational variable rather than as a simple intensity parameter offers a rational framework for optimizing EA protocols, improving reproducibility, and extending neuromodulation-based strategies to other diabetes-associated complications characterized by immune and metabolic dysregulation.
Correction to “Zhang GL, Liu Y, Liu YF, Huang XT, Tao Y, Chen ZH, Lai HL. Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome. World J Diabetes 2024; 15: 724-734 [PMID: 38680706 DOI: 10.4239/wjd.v15.i4.724]”. In the original publication, the bands of p-AMPK and AMPK in Figure 8A were placed wrongly. This error has now been corrected. In addition, the statistical symbol for the last group on the graph on the right side of Figure 8A has been corrected to “c”; “&” was incorrect.
We read with great interest the recent opinion review by Goyal et al on the cardiovascular implications of glycated hemoglobin (HbA1c) beyond its conventional role as a glycemic monitoring tool. This review argues that visit-to-visit HbA1c variability (usually quantified as the standard deviation, coefficient of variation, or variability independent of the mean across serial measurements) provides independent cardiovascular risk information beyond mean glycemia. To this, we would like to add a plausible endocrine mechanism that may partly explain this variability. We propose a two-tier model centered on dysregulation of the hypothalamic-pituitary-adrenal axis. First, sustained cortisol excess, as occurs in mild autonomous cortisol secretion from adrenal incidentalomas or in subclinical Cushing’s syndrome, acts across successive erythrocyte lifespans and may measurably shift mean HbA1c between clinic visits. Second, hyperglycemia-driven hypothalamic-pituitary-adrenal axis hyperactivity, mediated by pro-inflammatory cytokines, establishes a feed-forward loop that further perturbs the glycemic set point. We suggest that unexplained HbA1c variability, after exclusion of common causes such as medication changes, intercurrent illness, anemia, or altered erythrocyte lifespan, could prompt targeted hypothalamic-pituitary-adrenal axis screening in selected patients with additional clinical features of cortisol excess.
The recent study published in World Journal of Diabetes by Casillas et al provides compelling evidence that a high waist-to-height ratio (WtHR) cutoff of 0.5 in 39 young adults is associated with insulin resistance and endoplasmic reticulum (ER) stress in platelets. This association is characterized by elevated SERCA expression and increased protein kinase PERK and JNK phosphorylation. The work highlights the value of WtHR as an early marker of metabolic dysfunction. It also establishes platelets as a minimally invasive model for studying systemic ER stress. However, 2 critical aspects warrant further discussion. The first is the dynamic nature of SERCA regulation during disease progression, particularly given the small sample size. The second is the clinical significance of metabolic dysfunction in young adults with elevated WtHR, regardless of their body mass index classification. These findings provide novel perspectives for translational research regarding early metabolic risk stratification.
BACKGROUND Many biomarkers have been developed to facilitate early gestational diabetes mellitus (GDM) diagnosis, but they have multiple limitations, including low accuracy and constraints in detection methods. The majority of biomarkers are influenced by gestational age, sample sizes and types, and analytical methodologies. Thus, there is a need of more accurate biomarkers for early diagnosis. AIM To investigate the expression of the peroxiredoxin (PRDX) family in early pregnancy and its clinical value for predicting subsequent GDM. METHODS Plasma samples and clinical data were collected at < 12 weeks of gestation from 222 women who subsequently developed GDM (confirmed by the 75 g oral glucose tolerance test at 24-28 weeks) and 222 women who remained normoglycemic throughout pregnancy, using random sampling at our hospital between January 2019 and December 2025. Participants were assigned to the observation group and control group accordingly. Plasma PRDX (PRDX1-PRDX6) levels were measured by ELISA. Receiver operating characteristic curves were applied for the assessment of the diagnostic value of PRDXs for early GDM. Univariate and multivariate logistic regression analyses were performed to identify related independent risk factors. RESULTS Baseline characteristics [age, pre-pregnancy body mass index (BMI), mid-pregnancy BMI] and biochemical indicators (triglycerides, low-density lipoprotein-cholesterol, fasting blood glucose, glycated hemoglobin) were markedly higher in the GDM group (P < 0.05). Expression levels of all PRDX family members in plasma showed obvious elevations in the observation group (P < 0.05). PRDX1, PRDX4, and PRDX5 displayed high diagnostic value for early GDM, with areas under the curve of 0.757, 0.776, and 0.742, respectively, and a combined diagnostic area under the curve of 0.836. Univariate analysis identified 15 significant risk factors, and multivariate analysis revealed age, pre-pregnancy BMI, triglycerides, low-density lipoprotein-cholesterol, fasting blood glucose, glycated hemoglobin, PRDX1, and PRDX3 as independent risk factors for early GDM (P < 0.05). CONCLUSION All PRDX family members showed significantly elevated expression in early GDM. PRDX1, PRDX4, and PRDX5 exhibited substantial diagnostic value, while PRDX1 and PRDX3 were identified as independent risk factors.
BACKGROUND Adults presenting with ketosis or diabetic ketoacidosis at diabetes onset pose a diagnostic challenge because ketosis-prone (KP) type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADAs) share overlapping clinical features but require fundamentally different long-term management strategies. In many clinical settings, limited access to islet autoantibody testing further complicates early classification. AIM To characterize the clinical, metabolic, and endocrine features of ketosis-onset diabetes in adults and to identify potential non-antibody biomarkers to differentiate LADA from KP-T2DM and distinguish ketosis-onset from nonketotic diabetes. METHODS A total of 294 newly diagnosed adult patients were classified into LADA, KP-T2DM, and nonketotic T2DM groups. Clinical and metabolic characteristics were compared. Multivariable logistic regression was performed to identify factors associated with ketosis onset and LADA classification, and receiver operating characteristic analysis was used to evaluate the discriminatory performance of candidate biomarkers. RESULTS LADA accounted for 27.3% of ketosis-onset cases. Compared with patients with KP-T2DM, those with LADA exhibited significantly impaired β-cell function and lower insulin resistance. Multivariable analysis identified postprandial C-peptide as the strongest independent discriminator between LADA and KP-T2DM. Receiver operating characteristic analysis demonstrated that 2-hour C-peptide showed good discriminatory performance for differentiating LADA from KP-T2DM (area under the curve = 0.852). Other metabolic parameters, including high-density lipoprotein cholesterol, gamma-glutamyl transferase, alkaline phosphatase, free triiodothyronine, fasting plasma glucose, and homeostasis model assessment of insulin resistance, showed additional but more limited discriminatory value. CONCLUSION Among adults presenting with ketosis at diabetes onset, LADA represents a substantial proportion of cases and should be considered in the differential diagnosis. Readily available non-antibody biomarkers, particularly 2-hour postprandial C-peptide, demonstrated promising discriminatory performance for differentiating LADA from KP-T2DM, whereas other metabolic markers provided supplementary information. These findings may support the clinical evaluation of atypical diabetes in settings where autoantibody testing is unavailable; however, independent validation is required before routine clinical application.
The discovery of the incretin system and the subsequent development of pharmacotherapeutic agents to manipulate incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, as well as glucagon, with various drugs, have revolutionised the management of type 2 diabetes mellitus (T2DM) in the 21st century. The first few drug molecules in this group were the GLP-1 receptor agonists (GLP-1RA), which have been used for treating patients with T2DM in the past 2 decades, and newer molecules, including incretin polyagonists, are being added to the growing list of incretin-based drugs in recent years. Generally, these newer molecules possess longer biological half-lives and dosing intervals, better weight loss potentials, higher efficacy in glycemic control and possibly improved disease-modifying properties such as a higher chance for T2DM remission and better cardiometabolic outcomes. Therefore, newer incretin-based medications are currently preferred by many diabetologists and switching from older molecules to the newer ones is not uncommon in day-to-day clinical practice. However, outside the remit of randomised controlled trial settings, there is only limited evidence emerging from real-world data. A study by Kassem et al published in the World Journal of Diabetes provides us with robust evidence from a large real-world study of 18047 patients with T2DM from Israel on the benefits of switching from an old GLP-1RA to a newer agent, with a remarkable improvement in glycemic control. With the most up-to-date evidence, we update the rationale for switching GLP-1RA molecules in managing T2DM with a detailed review of the therapeutic benefits, including the anticipated cardiometabolic outcomes and cost benefit analysis from such switching in this editorial.
Glycated hemoglobin (HbA1c) remains the cornerstone biomarker for long-term glycemic control in diabetes mellitus, reflecting average plasma glucose over approximately three months. Beyond its diagnostic and monitoring utility, HbA1c has emerged as a robust predictor of cardiovascular disease, the leading cause of morbidity and mortality in individuals with diabetes. Epidemiological studies, including the United Kingdom Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications Trial, have consistently demonstrated a graded, near-linear relationship between HbA1c levels and macrovascular risk. However, the translation of glycemic control into cardiovascular benefit has proven complex. While early intensive glycemic control confers long-term cardiovascular protection, a phenomenon termed “metabolic memory” later trials such as ACCORD, ADVANCE, and VADT have highlighted the limitations and potential risks of aggressive HbA1c lowering, particularly in high-risk populations. Emerging evidence suggests that HbA1c variability, rather than mean levels alone, may independently contribute to cardiovascular outcomes through mechanisms involving oxidative stress, endothelial dysfunction, and inflammation. Furthermore, contemporary glucose-lowering therapies, including sodium-glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, reduce cardiovascular events largely independent of HbA1c reduction, challenging the primacy of HbA1c as a surrogate endpoint. This review critically appraises the evolving role of HbA1c in cardiovascular risk stratification, emphasizing the need for individualized glycemic targets and a broader, multifactorial approach to cardiovascular risk reduction in diabetes.
Chronic diabetic wounds represent a significant burden on global healthcare, characterized by their refractory nature and high risk of lower-limb amputation, which is mainly attributed to impaired angiogenesis and persistent endothelial dysfunction in a hostile hyperglycemic microenvironment. Mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as promising cell-free therapeutic options; however, their baseline bioactivity is often insufficient to achieve consistent clinical efficacy. Chen et al recently published a study in World Journal of Diabetes showing that fractional carbon dioxide (CO2) laser-based photothermal preconditioning of adipose-derived MSCs enhances the pro-angiogenic activity of Exos by enriching sphingosine-1-phosphate (S1P) cargo and activating endothelial S1P receptor 1/protein kinase B/hypoxia-inducible factor-1α signaling. In this editorial, we position these findings within the broader context of Exo engineering and preconditioning strategies for diabetic wound repair. We also highlight the conceptual distinction among physical, pharmacological and genetic preconditioning approaches, and discuss the specific advantages of fractional CO2 laser as a drug-free, dose-tunable and clinically familiar platform to enhance the functional potency and cargo composition of Exos rather than simply increase total Exos yield. We further outline key translational issues that remain to be addressed, including donor heterogeneity, parameter and dose standardization, and the integration of laser preconditioning into scalable good manufacturing practice compliant Exo production workflows. Overall, clinically available fractional CO2 laser systems offer a uniquely controllable preconditioning modality that can bridge the gap between promising preclinical data and real-world applications of MSC-Exos in diabetic wound healing, provided that their safety, reproducibility and long-term vascular effects are rigorously evaluated.
In this editorial, we discuss a significant recent study published in World Journal of Diabetes by Shao et al . Diabetic osteoporosis (DOP) is a severe skeletal complication of diabetes. Emerging evidence indicates that ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in osteoblast dysfunction and bone loss under hyperglycemic conditions. However, the precise mechanisms through which osteoblast ferroptosis can be effectively targeted for the treatment of diabetic osteopenia remain elusive. The study by Shao et al advances our understanding of DOP by demonstrating that endothelial cell-derived exosomes function as a natural delivery system that protects osteoblasts from high glucose-induced ferroptosis. The authors identify microRNA-335-3p (miR-335-3p) as the key molecular mediator within this protective mechanism, acting by directly targeting and suppressing prostaglandin endoperoxide synthase 2, a recognized marker of ferroptosis. Clinically, an inverse correlation was observed between serum miR-335-3p levels and disease severity, highlighting that miR-335-3p not only represents a potential therapeutic target but also a promising non-invasive biomarker for early detection and monitoring of DOP, thereby underscoring its translational relevance.
