Acta Diabetologica最新文献

{"title":"The cGAS-STING signaling axis in Type 2 diabetes-associated cognitive decline: from mitochondrial DNA sensing to neurodegeneration.","authors":"Nitish Nirala, Omkar Kumar Kuwar, Dhrubalochan Rana, Dibya Sundar Padhy, Ram Kumar Choudhary","doi":"10.1007/s00592-026-02802-5","DOIUrl":"https://doi.org/10.1007/s00592-026-02802-5","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is increasingly recognized as a major contributor to cognitive decline, substantially elevating the risk of dementia through mechanisms that extend beyond chronic hyperglycemia. Among the interconnected pathological processes underlying diabetic neurodegeneration, mitochondrial dysfunction has emerged as a pivotal upstream event that promotes oxidative stress, impairs mitophagy, and leads to the cytosolic release of mitochondrial DNA (mtDNA). Recent evidence identifies the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway as a critical innate immune sensor that detects aberrant cytosolic mtDNA and orchestrates sustained neuroinflammatory responses. Activation of the cGAS-STING axis initiates TBK1/IRF3- and NF-κB-dependent signaling, driving the production of type I interferons and pro-inflammatory cytokines that amplify glial activation, compromise blood-brain barrier (BBB) integrity, disrupt synaptic homeostasis, and suppress adult hippocampal neurogenesis, ultimately contributing to progressive cognitive impairment. Although the cGAS-STING pathway has been extensively investigated in infection, cancer, and autoimmune disorders, its mechanistic contribution to diabetes-associated cognitive decline remains insufficiently synthesized. This review proposes cGAS-STING as a central molecular hub that integrates mitochondrial damage with innate immune activation, thereby linking metabolic dysfunction to neurodegeneration. We critically evaluate current experimental and emerging clinical evidence and examine the interplay among cGAS-STING, mitochondrial quality control, neurovascular dysfunction, and key signaling networks, including AMPK/SIRT1/PGC-1α, the NLRP3 inflammasome, PI3K/Akt-mTOR, and autophagy. Finally, we discuss the therapeutic potential of targeting the cGAS-STING axis and identify major knowledge gaps that must be addressed to facilitate biomarker development and the development of disease-modifying interventions for T2DM-associated cognitive decline.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ceramides in metabolic syndrome: recent advances and therapeutic opportunities.","authors":"Jinrui Zhang, Yiting Wang, Xiaojun Liu","doi":"10.1007/s00592-026-02808-z","DOIUrl":"https://doi.org/10.1007/s00592-026-02808-z","url":null,"abstract":"<p><p>Ceramides are bifunctional molecules that act as both structural constituents of cellular membranes and bioactive effectors in sphingolipid signaling. Their metabolic perturbation is a hallmark of metabolic syndrome, such as obesity, insulin resistance, type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and atherosclerosis. Among the numerous ceramide species, the long-chain species C16:0 and C18:0 have garnered particular attention due to their robust pathogenic roles and strong associations with human disease. This review critically examines the potential of ceramides as predictive biomarkers and provides novel translational perspectives for the clinical management of metabolic syndrome.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance and biological role of circFNDC3B in diabetic retinopathy.","authors":"Fang Liu, Dongxu Guan, Zhiyu Yang, Dan Zou","doi":"10.1007/s00592-026-02803-4","DOIUrl":"https://doi.org/10.1007/s00592-026-02803-4","url":null,"abstract":"<p><strong>Objective: </strong>This paper investigates the clinical significance and role of circFNDC3B in diabetic retinopathy (DR).</p><p><strong>Methods: </strong>Expression levels of circFNDC3B, miR-578, and PIK3CA were detected in serum from DR patients and in HRMECs under high glucose (HG) conditions via qRT-PCR. Diagnostic value of circFNDC3B were assessed using ROC curves and logistic regression analysis. Cell proliferation, migration, and invasion capabilities of HRMECs were assessed using CCK-8 assays and Transwell experiments. Cellular inflammation was measured via ELISA. The interrelationship among circFNDC3B, miR-578, and PIK3CA was validated through dual-luciferase reporter and RNA immunoprecipitation experiments.</p><p><strong>Results: </strong>In the serum of patients with DR, circFNDC3B was markedly upregulated, and it has potential as a diagnostic biomarker for DR. miR-578 was identified as a direct target miRNA of circFNDC3B, showing downregulated expression in both DR patient serum and HG-induced HRMECs. Inhibition of miR-578 partially reversed the suppression of circFNDC3B downregulation on proliferation, migration, invasion, and inflammatory responses in HG-induced HRMECs circFNDC3B regulated PIK3CA expression by sponging miR-578.</p><p><strong>Conclusion: </strong>circFNDC3B may serve as a potential biomarker for DR diagnosis and treatment. Its involvement in HG-induced HRMEC injury, through interacting with miR-578, provides new insights into the pathogenesis of DR.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe diabetic ketoacidosis unmasking a low-oxygen-affinity haemoglobin variant in an infant: a case report.","authors":"Benedetta Mainetti, Stefania Bigoni, Marina Fabris, Enrico Valletta","doi":"10.1007/s00592-026-02777-3","DOIUrl":"https://doi.org/10.1007/s00592-026-02777-3","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap in early cardio-renal risk prevention in type 2 diabetes: evidence, guidelines, and real-world insights from the PRECARE NO LiMITS initiative.","authors":"Loredana Bucciarelli, Maria Elena Lunati, Cesare Berra, Nadia Cerutti, Antonio Conti, Renata Ghelardi, Angela Girelli, Paola Morpurgo, Antonio Rossi, Cristiana Scaranna, Camilla Tinari, Paolo Fiorina","doi":"10.1007/s00592-026-02798-y","DOIUrl":"https://doi.org/10.1007/s00592-026-02798-y","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is associated with a substantial burden of cardiovascular and renal complications. Although current evidence supports early implementation of organ-protective strategies, therapeutic inertia and uncertainty regarding guideline implementation may delay treatment intensification. The goal of this review is to discuss the rationale for early cardiorenal protection in T2D and to explore real-world perspectives on the use of SGLT2 inhibitors and GLP-1 receptor agonists through insights from the PRECARE NO LiMITS initiative. This narrative review integrates current evidence with exploratory findings from the PRECARE NO LiMITS project, a multicentre educational initiative involving diabetologists from ten diabetes centres in Lombardy, Italy. The initiative included two descriptive clinician survey rounds, conducted at baseline (T0) and after six months (T1), together with moderated expert discussions. At T1, a higher proportion of respondents reported considering SGLT2 inhibitor initiation in a greater proportion of patients with early cardiorenal risk markers, including albuminuria and mildly reduced eGFR, even in the absence of established cardiovascular or renal disease. Survey responses also suggested greater consideration of risk-based treatment strategies extending beyond glycaemic control alone. Persistent perceived barriers included reliance on HbA1c as a primary driver of treatment intensification, uncertainty regarding the timing and implementation of organ-protective therapies, and concerns related to treatment complexity and access. Given the descriptive nature of the survey, differences between T0 and T1 should be interpreted as exploratory. Overall, these exploratory observations, considered alongside current evidence and guideline recommendations, highlight the potential value of a proactive approach to T2D management focused on early identification of cardiorenal risk and appropriate consideration of organ-protective therapies. Educational initiatives, multidisciplinary collaboration, and improved translation of guideline recommendations into routine clinical practice may help address therapeutic inertia and facilitate timely, individualised treatment decisions.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between peripheral blood biomarkers and diabetic macular edema.","authors":"Na, Ruowen Gong, Ruyi Han, Han Li, Meidie Pan, Xin Yang, Gezhi Xu, Wei Liu","doi":"10.1007/s00592-026-02799-x","DOIUrl":"https://doi.org/10.1007/s00592-026-02799-x","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the association between peripheral blood biomarkers and DME severity.</p><p><strong>Methods: </strong>This cross-sectional study included 227 consecutive patients (305 eyes) with DME and 94 controls (94 eyes). DME was classified into early, advanced, and severe stages based on spectral-domain optical coherence tomography. Peripheral blood samples were analyzed, and the association between peripheral blood biomarkers and DME severity was evaluated using generalized estimating equations.</p><p><strong>Results: </strong>Compared with the control group, patients with DME exhibited significantly lower values in red blood cell (RBC) count (P < 0.001), hemoglobin (P < 0.001) and hematocrit (P < 0.001), as well as significantly higher values in white blood cell count (P < 0.001), neutrophil count (P < 0.001), monocyte count (P < 0.001), fibrinogen level (P < 0.001), D-dimer level (P = 0.015), neutrophil-to-lymphocyte ratio (P < 0.001), and monocyte-to-lymphocyte ratio (P < 0.001). Moreover, advanced or severe DME was associated with RBC count (10^12/L) (OR (95% CI) = 0.49 (0.288, 0.834), P = 0.009), hemoglobin (g/L) (OR (95% CI) = 0.978 (0.959, 0.996), P = 0.02), and hematocrit (%) (OR (95% CI) = 0.919 (0.859, 0.985), P = 0.016).</p><p><strong>Conclusions: </strong>DME is characterized by reduced RBC measures and elevated inflammatory indices. Decreased RBC measures could serve as potential markers of DME severity.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond medication adherence: bisphenol exposure and its relationship with good glycemic control in type 2 diabetes.","authors":"Julia Matzenbacher Dos Santos, Jason Dechant, Jiayi Zhu, Tapan Seth, Jeffrey Rohay, Thiago Gomes Heck, Jacqueline Dunbar-Jacob","doi":"10.1007/s00592-026-02794-2","DOIUrl":"https://doi.org/10.1007/s00592-026-02794-2","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of type 2 diabetes (T2D) continues to rise alongside complications associated with chronic hyperglycemia. While antihyperglycemic medications are central to glycemic control, exposure to bisphenol-A (BPA) and bisphenol-S (BPS), used to coat food packages, may influence disease progression. This study aimed to test a dietary survey to estimate BPA and BPS among T2D individuals and evaluate BPA and BPS associations with levels of glycated hemoglobin (HbA1C).</p><p><strong>Methods: </strong>Medication adherence of 382 T2D patients (63.68 ± 10.52 yrs., 7.43 ± 1.36% HbA1C) treated with oral anti-hyperglycemic therapy was assessed with electronic Drug Exposure Monitors. Dietary behavior was evaluated using the Connor dietary survey. Plasma BPA and BPS levels were measured using ELISA assay. Multivariate analyses examined variables related with HbA1C, accounting for modifiable (BMI, diet, physical activity, medication adherence, BPA/BPS levels) and non-modifiable factors (age, sex, race).</p><p><strong>Results: </strong>The Connor dietary survey did not effectively estimate BPS or BPA levels. BPS, not BPA, was associated with HbA1C when adjusted by non-modifiable variables (β-coefficient = 0.14, P = 0.045), along with medication adherence (β-coefficient = -0.12, P = 0.048). However, when modifiable variables were included in the adjustment, cholesterol and saturated fats intake (β-coefficient = -0.14, P = 0.045), and medication adherence (β-coefficient = -0.16, P = 0.012) were associated with HbA1C.</p><p><strong>Conclusion: </strong>Levels of BPS are positively associated with HbA1c, even after accounting for non-modifiable factors, diet, and medication adherence, well-established determinants of glycemic control in T2D. Strategies aimed at reducing BPS exposure may complement antihyperglycemic therapy and diet to control HbA1C in T2D.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of circulating osteocalcin-expressing monocytes by glucagon like peptide-1 receptor agonists in type 2 diabetes: an exploratory pilot study.","authors":"Andrea Carafa, Rosario Luigi Sessa, Rocco Amendolara, Simona Zampetti, Carmen Mignogna, Francesca Sciarra, Luca D'Onofrio, Renata Risi, Mary Anna Venneri, Ilaria Cavallari, Ernesto Maddaloni, Raffaella Buzzetti","doi":"10.1007/s00592-026-02778-2","DOIUrl":"https://doi.org/10.1007/s00592-026-02778-2","url":null,"abstract":"<p><strong>Context: </strong>The phenotypic drift of circulating monocytes toward osteoblast-like cells expressing osteocalcin (OCN) has been linked to vascular calcification in individuals with type 2 diabetes (T2D). The synergistic action of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and metformin may reduce the cardiovascular risk by modulating OCN-expressing monocytes, representing a novel mechanism of cardiovascular protection.</p><p><strong>Objective: </strong>To investigate the impact of GLP-1 RA add-on metformin therapy on the percentage of circulating CD14⁺OCN⁺ monocytes.</p><p><strong>Research design and methods: </strong>This longitudinal study enrolled patients with T2D receiving metformin monotherapy who either initiated GLP-1 RA therapy (Group A, n = 7) or did not (Group B, n = 28). Clinical parameters and circulating CD14+OCN+ cell levels were assessed at baseline (V0), after 1 week (V1) and after 12 weeks (V2). In vitro experiments were conducted using peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n = 10), treated with metformin or exendin-4 for 24 h.</p><p><strong>Results: </strong>In group A, the percentage of CD14+OCN+ significantly decreased from baseline (4.5 [2.5-7.6]) to V2 (2.2 [1.73-4.9]% p = 0.019). This reduction was already significant at V1 (p = 0.039). No significant change over time was observed in Group B (p = 0.31). In vitro treatment of PBMCs with metformin significantly reduced the percentage of CD14⁺OCN⁺ cell (- 34.9%, p < 0.0001), whereas exendin-4 yielded a non-significant downward trend (- 8.5%, p = 0.1).</p><p><strong>Conclusion: </strong>GLP-1 RA add-on therapy to metformin reduces OCN expression in circulating monocytes in patients with T2D. In vitro data suggest that this effect might not result from a direct effect on mononuclear cells, but rather from indirect systemic mechanisms that warrant further investigation. These findings identify OCN-expressing monocytes as a potential novel therapeutic target for GLP-1 RA to reduce cardiovascular risk in T2D.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telemedicine and teledentistry to manage medical and dental professional collaboration while identifying a link between periodontitis and diabetes mellitus.","authors":"Kazuhiko Kotani","doi":"10.1007/s00592-026-02797-z","DOIUrl":"https://doi.org/10.1007/s00592-026-02797-z","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HbA1c reconsidered: glycated haemoglobin in the era of dynamic erythrocyte glucose metabolism.","authors":"Ming-Yu Hsieh","doi":"10.1007/s00592-026-02800-7","DOIUrl":"https://doi.org/10.1007/s00592-026-02800-7","url":null,"abstract":"<p><p>Glycated haemoglobin (HbA1c) has been the standard biomarker of long-term glycaemic control for four decades. It rests on a tacit assumption: that non-enzymatic haemoglobin glycation is governed chiefly by mean plasma glucose, with erythrocyte intracellular glucose in passive equilibrium with plasma. This requires erythrocyte glucose uptake-and thus glucose transporter 1 (GLUT1) expression-to be effectively constant. The 2026 demonstration that chronic hypoxia upregulates erythrocyte GLUT1 approximately twofold and per-cell glucose uptake approximately threefold, together with evidence that the band 3 N-terminus acts as a bidirectional metabolic switch responsive to haemoglobin oxygenation, challenges this assumption. We propose that HbA1c is better understood as integrating erythrocyte intracellular glucose exposure, a quantity predicted to diverge from plasma glucose when the erythrocyte oxygen environment or red cell turnover is altered. We review reported discordance in high-altitude populations, obstructive sleep apnoea, cyanotic congenital heart disease, critical illness and chronic kidney disease, and propose testable predictions and a research roadmap. The framework is intended to complement, not replace, established explanations such as altered red cell survival, erythropoiesis, iron status and analytical interference. No human study has yet measured erythrocyte GLUT1 expression, intracellular glucose exposure and HbA1c discordance concurrently; the framework is therefore presented as a hypothesis for prospective testing rather than as a basis for changing clinical practice.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}