Acta Diabetologica最新文献

{"title":"Adipose mesenchymal stem cell-derived extracellular vesicles regulate PINK1/parkin-mediated mitophagy to repair high glucose-induced dermal fibroblast senescence and promote wound healing in rats with diabetic foot ulcer.","authors":"Yinji Luo, Qijie Guo, Chang Liu, Yuxuan Zheng, Yichong Wang, Bin Wang","doi":"10.1007/s00592-024-02422-x","DOIUrl":"https://doi.org/10.1007/s00592-024-02422-x","url":null,"abstract":"<p><strong>Aims: </strong>Diabetic foot ulcers (DFUs) cause prominent morbidity and mortality. Adipose mesenchymal stem cell (ASC)-derived extracellular vesicles (EVs) show property in facilitating diabetic wound healing, and we explored their role in DFU rats.</p><p><strong>Methods: </strong>ASCs were cultured in vitro, passaged and then identified by flow cytometry and induction of osteogenic/adipogenic differentiation. ASC-EVs were extracted and identified. DFU rat model was treated with ASC-EVs. High glucose (HG)-induced rat dermal fibroblasts were treated with ASC-EVs or 3-MA and sh-PINK1 plasmid in vitro. Wound healing was observed. Histological changes, inflammatory cytokines (TNF-α, IL-1β), and α-SMA and p21 double-positive cell level were assessed by HE staining, ELISA, and immunofluorescence. Mitochondrial membrane potential (MMP), cell viability and senescence, and ROS production in cells were assessed by fluorescence dye JC-1, CCK-8, SA-β-gal staining, and ROS kit. p21, LC3II/I, p62, PINK1 and parkin protein levels were determined by Western blot.</p><p><strong>Results: </strong>DFU rats had slow wound healing and elevated levels of IL-1β, TNF-α, α-SMA and p21 double-positive cells, and SA-β-gal, while HG-induced cells had weakened viability, elevated ROS, SA-β-gal, p21 and p62 protein levels, and decreased LC3II/I, PINK1 and parkin protein levels and MMP, which were reversed by ASC-EVs. HG inhibited mitophagy by suppressing the PINK1/parkin pathway to accelerate dermal fibroblast senescence. The PINK1/parkin pathway inhibition partly mitigated the effect of ASC-EVs. ASC-EVs promoted mitophagy by activating the PINK1/parkin pathway in vivo.</p><p><strong>Conclusions: </strong>ASC-EVs mediated mitophagy by activating the PINK1/parkin pathway, thereby impeding HG-induced rat dermal fibroblast senescence and promoting wound healing in DFU rats.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827143","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":"Factors associated with intensive care unit admission due to diabetic ketoacidosis in adults: a validated predictive model.","authors":"Fernando Sebastian-Valles, Andrés Carlos Von Wernitz Teleki, Maria Sara Tapia-Sanchiz, Victor Navas-Moreno, Marta Lopez-Ruano, Carmen Martinez-Otero, Elena Carrillo-López, Carolina Sager-La Ganga, Juan José Raposo-López, Selma Amar, Sara González Castañar, Jose Alfonso Arranz-Martin, Carmen Del Arco, Mónica Marazuela","doi":"10.1007/s00592-024-02421-y","DOIUrl":"https://doi.org/10.1007/s00592-024-02421-y","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to develop a predictive model capable of determining the need for intensive care unit (ICU) admission of patients with diabetic ketoacidosis (DKA) during their assessment in the Emergency Department.</p><p><strong>Methods: </strong>This is an observational study of consecutive cases including all adult patients diagnosed with DKA at a tertiary hospital between 2010 and 2024. Variables from medical history, physical examination, and laboratory tests at admission were collected and studied for their association with ICU admission. The sample was divided into two randomized parts: one to build a logistic regression model and another to validate it.</p><p><strong>Results: </strong>Two hundred and thirty-one DKA events were included. Individuals had a mean age of 49.6 ± 19.9 years and 50.2% were male. Forty-eight point five percent of cases required ICU admission, and 30-day mortality was 4.8%. The best model to predict ICU admission included Glasgow Coma Scale (odds ratio [OR] = 0.64, p = 0.003), pH (OR = 0.0088, p = 0.005), bilirubin (OR = 0.13, p = 0.036), bicarbonate (OR = 0.0091, p = 0.013), and pH-bicarbonate interaction (OR = 3.78, p = 0.015). The model had an R² of 0.561, and the area under the curve (AUC) in the validation cohort was 0.842. Internal validation by bootstrap resampling showed an AUC = 0.871.</p><p><strong>Conclusion: </strong>Variables associated with the severity of acidosis in patients with DKA predict the need for ICU admission better and earlier than other clinical variables.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827148","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":"Incidence of type 1 diabetes in Gansu Province, Northwest China from 2018 to 2022: a multicenter, hospitalization-based study.","authors":"Yue Zhang, Xiaoning Liu, Shaolun Yang, Xueni Yang, Mengmeng Shang, Yujie Zhang, Limin Tian","doi":"10.1007/s00592-024-02427-6","DOIUrl":"https://doi.org/10.1007/s00592-024-02427-6","url":null,"abstract":"<p><strong>Objective: </strong>To survey the epidemiology of type 1 diabetes in all age groups living in the Gansu Province, China during 2018-2022.</p><p><strong>Methods: </strong>Using the data from the Gansu Province Health Commission Information Center and medical records, the crude incidence and 95%CI were calculated by region, age group, and sex assuming a Poisson distribution. The incidence differences were evaluated using the χ2 test. Spearman correlation was used to analyze the relation between latitude and incidence. The seasonality was analyzed using concentration, seasonal index and circular distribution method.</p><p><strong>Results: </strong>1393 cases of newly diagnosed type 1 diabetes were ascertained. The crude incidence of type 1 diabetes per 100,000 person-years in all individuals in Gansu Province was 1.09(95% confidence interval 1.03 to 1.15). The estimated incidence per 100,000 person-years by age group was 1.39 (95%CI:1.24-1.54) for 0-14 years, 3.58 (95%CI:3.33-3.83) for 15-29 years, 0.33(95%CI:0.29-0.37) for ≥ 30 years, with a peak in age group 15-19 years. There was a difference between males and females. Incidence of type 1 diabetes in Gansu Province was strongly correlated with latitude among children aged 0-29 years, and all age groups, but such correlation was not observed in adults aged ≥ 30 years. The seasonality of the type 1 diabetes is not obvious.</p><p><strong>Conclusion: </strong>The incidence of type 1 diabetes was relatively lower from 2018 to 2022 in Gansu Province, with variations across different regions and a positive correlation with latitude observed in all age groups. The incidence peak was noted in the 15-19 years group, and the incidence among males was higher than in females in all age groups. There was no significant seasonal variation in the incidence of type 1 diabetes.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816974","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":"Improving glycaemic control in children under 3 years using MiniMed™ 780G in SmartGuard™ AHCL with diluted insulin: a case series report.","authors":"Phuong Phan, Justine Cunningham, Ohn Nyunt, Charles F Verge, Helen Woodhead, Amy Wanaguru, Kristen A Neville","doi":"10.1007/s00592-024-02434-7","DOIUrl":"https://doi.org/10.1007/s00592-024-02434-7","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811870","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":"The potential of precision diabetology for type 2 diabetes treatment-evidence from a meta-regression for all-cause mortality from large cardiovascular outcome trials.","authors":"Oliver Kuss, Michael Roden, Sabrina Schlesinger, Annika Hoyer","doi":"10.1007/s00592-024-02425-8","DOIUrl":"https://doi.org/10.1007/s00592-024-02425-8","url":null,"abstract":"<p><strong>Aims: </strong>Two prerequisites must be met for the precision treatment approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in case of treatment heterogeneity, clinical predictors to identify people who would benefit from one treatment more than from others must be available. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. We recently applied this approach to the treatment of type 2 diabetes for the clinical outcomes of glycaemic control and body weight and repeat it for the clinical outcome of all-cause mortality.</p><p><strong>Methods: </strong>We performed a meta-regression analysis using digitalized individual participant information on time to death from 10 large cardiovascular outcome trials (7563 deaths from 99,746 participants) on DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors with respect to the variability of all-cause mortality and its potential predictors after treatment.</p><p><strong>Results: </strong>The adjusted difference in log(SD) values of time to death between the verum and placebo arms was -0.036 (95%-CI: -0.059; -0.013), showing larger variability of time to death in the placebo arms. No clinical predictors were found to explain treatment heterogeneity.</p><p><strong>Conclusions: </strong>This analysis suggests that the potential of the precision treatment approach in type 2 diabetes is low, at least with regard to improvement of all-cause mortality in population with high cardiovascular risk. This extends our previous findings for the clinical outcomes of glycaemic control and body weight.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811871","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":"Cluster-based subgroups of prediabetes and its association with prediabetes progression and regression: a prospective cohort study.","authors":"Yan Liu, Yu Liu, Min Zhang, Xinchen Wang, Xiaoying Zhou, Haijian Guo, Bei Wang, Duolao Wang, Zilin Sun, Shanhu Qiu","doi":"10.1007/s00592-024-02433-8","DOIUrl":"https://doi.org/10.1007/s00592-024-02433-8","url":null,"abstract":"<p><strong>Background: </strong>Cluster analysis provides an effective approach in stratifying prediabetes into different subgroups; however, the association of the cluster-based subgroups with prediabetes progression and regression has not been investigated. We aimed to address this issue in a Chinese population.</p><p><strong>Methods: </strong>A total of 4,128 participants with prediabetes were included to generate cluster-based subgroups of prediabetes based on age, body mass index (BMI), triglyceride-and-glucose (TyG) index, and hemoglobin A1c (HbA1c), using a k-means clustering model. Among them, 1,554 participants were followed-up for about three years to ascertain prediabetes progression and regression. Their association with the cluster-based subgroups of prediabetes was assessed using multinomial logistic regression analyses.</p><p><strong>Results: </strong>Three clusters of prediabetes were identified among the 4,128 participants, with cluster 0, 1 and 2 accounting for 28.0%, 31.4% and 40.6%, respectively. Participants with prediabetes were featured by the youngest age and the lowest HbA1c in cluster 0, the highest BMI and TyG index in cluster 1, and the oldest age and the lowest BMI in cluster 2. After multivariable-adjustment, both cluster 1 [odds ratio (OR) 3.31, 95% confidence interval (CI): 2.01-5.44] and cluster 2 (OR 2.58, 95% CI: 1.60-4.18) were associated with increased odds of progression to diabetes when compared with cluster 0. They were also associated with decreased odds of regression to normoglycemia (OR 0.54, and 0.56, respectively).</p><p><strong>Conclusions: </strong>Prediabetes participants featured by older age, higher degree of insulin resistance, higher BMI and worse glycemic condition had higher probability of progression to diabetes but lower chance of regression to normoglycemia.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811839","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":"High serum EDA concentration is associated with metabolic syndrome and its determinants.","authors":"Xia Deng, Yanyan Li, Tian Gu, Xunan Wu, Ziyan Sun, Haoxiang Li, Ling Yang, Guoyue Yuan","doi":"10.1007/s00592-024-02408-9","DOIUrl":"https://doi.org/10.1007/s00592-024-02408-9","url":null,"abstract":"<p><strong>Background: </strong>Ectodysplasin A (EDA) is a novel hepatokine that plays a role in multiple metabolic-related diseases. The aim of this study was to investigate the association between serum EDA levels and metabolic syndrome (MetS).</p><p><strong>Methods: </strong>A total of 348 subjects, 258 patients with MetS and 90 healthy controls were enrolled. Serum EDA levels were measured using an enzyme-linked immunosorbent assay (ELISA). The correlation between EDA and various metabolic components was assessed.</p><p><strong>Results: </strong>The serum EDA levels of subjects with metabolic syndrome (MetS) were significantly higher than those without [323.78 (259.68-400.74) vs. 254.82 (182.68-347.88) pg/mL, P < 0.001]. The serum EDA level increases with the increase in metabolic score. The linear regression model revealed that age, blood pressure, fasting insulin (FIns), high-density lipoprotein cholesterol (HDL-C), and HOMA-IR were independent factors influencing EDA levels. Furthermore, in the logistic regression model, subjects in the highest tertile of EDA had a significantly higher risk of MetS, higher blood pressure, hyperglycemia, and lower HDL-C compared to those in the lowest tertile. This conclusion remained valid after adjusting for multiple confounding factors.</p><p><strong>Conclusions: </strong>The research results for the first time found that the circulating EDA levels in patients with metabolic syndrome were significantly elevated and associated with hypertension, hyperglycemia, lower HDL-C, and insulin resistance risk, indicating that EDA may play a role in the occurrence of metabolic syndrome and may be a potential therapeutic target for metabolic syndrome.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805946","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":"The irreversible, towards fatalic neuropathy: from the genesis of diabetes","authors":"Bhaskar Pal,&nbsp;Rashmi Ghosh,&nbsp;Raktimava Das Sarkar,&nbsp;Gouranga Sundar Roy","doi":"10.1007/s00592-024-02429-4","DOIUrl":"10.1007/s00592-024-02429-4","url":null,"abstract":"<div><p>Diabetic neuropathy is the most prevalent diabetes-associated complication that negatively impacts the quality of life of the patients. The extensive complications of diabetic peoples in the world are the leading cause of neuropathic pain, and over-activation of different biochemical signalling process induces the pathogenic progression and are also corresponding the epidemic painful symptom of diabetic neuropathy. The main prevalent abnormality is neuropathy, which further causing distal symmetric polyneuropathy and focal neuropathy. The exact pathological complication of diabetes associated neuropathic algesia is still unclear, but the alteration in micro-angiopathy associated nerve fibre loss, hyper polyol formation, MAPK signalling, WNT signalling, tau-derived insulin signalling processes are well known. Furthermore, the post-translational modification of different ion channels, oxidative and nitrosative stress, brain plasticity and microvascular changes can contributes the development of neuropathic pain. However, in the current review we discussed about these pathogenic development of neuropathic pain from the genesis of diabetes, and how diabetes affects the physiological and psychological health, and quality of life of the patients. Furthermore, the treatment of diabetic neuropathy with conventional monotherapy and emerging therapy are discussed. In addition, the treatment with phytochemical constituents their mechanisms and clinical evidences are also reported. The future investigation is required on pathological alteration occurs in neuropathic individuals, and on molecular mechanisms as well as the adverse effect of phytochemicals to determine all aspects of neuropathic algesia including effective treatments, which will prevents the sympathetic pain in patients.</p></div>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"62 2","pages":"139 - 156"},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783491","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":"Pregnancy outcomes with the pregestational use of Minimed 780G compared to Minimed 640G: findings from a multicenter cohort study.","authors":"Verónica Perea, Carmen Quirós, María Teresa Herrera-Arranz, Sharona Azriel-Mira, Ana M Wägner, Pilar Beato-Vibora, Berta Soldevila, Beatriz Barquiel, Rosa Márquez Pardo, Gonzalo Díaz-Soto, Maria José Picón, Natalia Colomo, Judit Amigó, Elisenda Climent, María Durán-Martínez, Rosa Corcoy, Mercedes Codina, Martín Cuesta, Begoña Vega Guedes, Irene Vinagre","doi":"10.1007/s00592-024-02430-x","DOIUrl":"https://doi.org/10.1007/s00592-024-02430-x","url":null,"abstract":"<p><strong>Aim: </strong>To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using Minimed™ 780G (MM780G) with those women using Minimed™ 640G (MM640G) since before pregnancy.</p><p><strong>Methods: </strong>Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c, time spent within (TIRp), below (TBRp) and above (TARp) the pregnancy-specific glucose range 3.5-7.8 mmol/L (63-140 mg/dL) and glucose variability (CV).</p><p><strong>Results: </strong>Sixty-nine women were included (MM780G n = 40). At baseline, MM640G users had higher rates of severe hypoglycemia before pregnancy, without other between-group differences. The MM780G group had higher TIRp and lower TARp, TBRp and CV, but similar HbA1c in the first trimester of gestation. TBRp and CV remained significantly higher in the MM640G group throughout pregnancy. Higher HbA1c was observed in the MM780G group compared to the MM640G (6.28 ± 0.53% [45.1 ± 5.8 mmol/mol] vs. 5.97 ± 0.62 [41.8 ± 6.8], p = 0.003) in the second trimester. There were no differences in the mean change in HbA1c from the first to the third trimester of gestation between groups. MM780G users were more likely to have large-for-gestational-age infants (OR_adjusted 4.85, 95% CI 1.46-16.13, p = 0.010), macrosomia (OR_adjusted 12.17, 95% CI 1.49-99.72, p = 0.020) and cesarean section (OR_adjusted 4.19, 95% CI 1.34-13.11, p = 0.014) than the MM640G group.</p><p><strong>Conclusions: </strong>Pregestational use of MM780G led to an initial improvement in TIRp, but this was not sustained in the second and third trimesters, with a 4-fold increased risk of delivering a LGA infant and undergoing cesarean section compared to MM640G users.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765339","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":"Th22 cells promote the transition from homeostatic to reactive microglia in diabetic encephalopathy.","authors":"Sheng-Xue Yu, Hong Dan Yu, Yu-Fei Wang, Tie-Feng Yao, Song-Ze Lv, Yan-Chuan Wang, Jun-Qi Li, Wen-Qiang Liu, Jia-Yuan Ding, Xue-Zheng Liu, Zhong-Fu Zuo, Wan-Peng Liu","doi":"10.1007/s00592-024-02384-0","DOIUrl":"https://doi.org/10.1007/s00592-024-02384-0","url":null,"abstract":"<p><strong>Background: </strong>Diabetic encephalopathy (DE) is one of the most serious complications of diabetes mellitus (DM), and its pathogenesis has not yet been clarified. Th22 cells are a newly discovered class of CD4⁺ T cells that play important roles in inflammatory, autoimmune and infectious diseases. However, it is unclear whether Th22 cells are involved in the pathogenesis of DE.</p><p><strong>Methods: </strong>We established a T2DM mouse model in vivo and cocultured Th22 cells with microglia under high glucose (HG) conditions in vitro. Cognitive dysfunction was evaluated using the Morris water maze (MWM) test; blood‒brain barrier (BBB) integrity was evaluated using the Evans blue (EB) extravasation assay; Th22 cells and IL-22 receptors were detected by immunofluorescence; and IL-1β, TNF-α, iNOS, CD86, Arg-1, and CD206 protein expression was measured by Western Blot (WB) analysis.</p><p><strong>Results: </strong>Th22 cells passed through the BBB into the hippocampus and secreted interleukin-22 (IL-22), and the mice subsequently exhibited decreased learning and memory abilities. In the DE model, IL-22 promoted the transformation of homeostatic microglia into reactive microglia as well as the inflammatory response. Additionally, coculture of Th22 cells with BV2 microglia cultured under HG conditions increased the production of proinflammatory cytokines, and the microglia showed reactive changes. Mechanistically, IL-22Rα1 acted as a ligand, and IL-22 bound to IL-22Rα1 on microglia to drive primary microglia-induced inflammatory responses. Interestingly, interleukin-22 binding protein (IL-22BP) directly binds to IL-22Rα1 on microglia to inhibit the proinflammatory effects of IL-22.</p><p><strong>Conclusion: </strong>Th22 cells secrete IL-22 after passing through the BBB into the hippocampus and promote the transformation of homeostatic microglia into reactive microglia, which induces an inflammatory response, exacerbates learning and memory impairment and cognitive deficits, and contributes to and accelerates the development of DE.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765360","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}