Wei-Zhen Tang, Zhe-Ming Kang, Yi-Fan Zhao, Qin-Yu Cai, Beng-Ning Deng, Zhi-Jian Zhou, Wen-Xin Deng, Wei-Ze Xu, Tai-Hang Liu, Lan Wang
{"title":"Perinatal adverse outcomes in twin pregnancies with preeclampsia complicated by distinct gestational diabetes subtypes.","authors":"Wei-Zhen Tang, Zhe-Ming Kang, Yi-Fan Zhao, Qin-Yu Cai, Beng-Ning Deng, Zhi-Jian Zhou, Wen-Xin Deng, Wei-Ze Xu, Tai-Hang Liu, Lan Wang","doi":"10.1007/s00592-025-02444-z","DOIUrl":"https://doi.org/10.1007/s00592-025-02444-z","url":null,"abstract":"<p><strong>Background: </strong>The impact of gestational diabetes mellitus (GDM) complicated with preeclampsia (PE) on perinatal outcomes in twin pregnancies, particularly across different GDM subtypes, remains unclear.</p><p><strong>Methods: </strong>This case-control study included 1,263 twin pregnancies with GDM and categorized participants as follows: (i) GDM without PE and GDM with PE groups, and (ii) GDM subgroups based on oral glucose tolerance test (OGTT) values at different time points, including GDM-IFH, GDM-IPH, and GDM-CH. Initially, the study investigated risk factors for PE occurrence in women with GDM. Subsequently, univariate and multivariate logistic regression analyses were conducted to explore the impact of GDM with PE on perinatal outcomes in twin pregnancies compared to GDM without PE. Stratified analyses and interaction effects were also examined to assess the risk of adverse perinatal outcomes in GDM twin pregnancies with various maternal characteristics combined with PE. Additionally, the study assessed the influence of aspirin on the GDM with PE group. Based on OGTT values, the study further investigated their impact on perinatal outcomes in the GDM with PE group and examined the influence of different GDM subtypes on perinatal outcomes in twin pregnancies with GDM and PE.</p><p><strong>Results: </strong>Baseline characteristics of twin pregnancies with GDM indicated that pre-pregnancy BMI (PBMI) (p < 0.001), weight gain during pregnancy (p < 0.001), nulliparity (p = 0.029), and the use of IVF (p = 0.023) may be risk factors for the occurrence of PE in GDM. Additionally, GDM with PE increased the risk of Intrahepatic Cholestasis of Pregnancy (ICP) (OR 2.00), hypoproteinemia during pregnancy (OR 4.18), anemia during pregnancy (OR 2.34), and MICU admission (OR 5.43) compared to GDM without PE. Regarding neonatal outcomes, the GDM with PE group had significantly higher risks of neonatal hyperbilirubinemia (OR 1.97), preterm labor (OR 1.58), and NICU admission (OR 2.32). In the GDM with PE group, aspirin significantly reduced the risk of preterm labor. Further research indicated that glucose values significantly affected the occurrence of ICP, hypoproteinemia during pregnancy, and anemia during pregnancy in the GDM with PE group. Subgroup analysis based on OGTT glucose values classified GDM subtypes showed that different GDM subtypes are closely related to the risk of hypoproteinemia during pregnancy, neonatal hyperbilirubinemia, and preterm labor in both GDM without PE group and GDM with PE groups. Particularly in GDM-IPH and GDM-CH subtypes, PE combined with GDM significantly increased the risks associated with ICP, hypoproteinemia during pregnancy, and MICU admission. Moreover, GDM-IPH combined with PE significantly increased the risks of anemia during pregnancy, NICU admission, and neonatal hyperbilirubinemia, while GDM-CH combined with PE also significantly increased the risk of preterm birth.</p><p><strong>Conclusion: ","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633343","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}
Anjana J Menon, Monisha Selva, G Sandhya, Sadhana Singh, M L Abhishek, Albert Stezin, Jonas S Sundarakumar, Latha Diwakar, Thomas Gregor Issac
{"title":"Understanding the link between insulin resistance and cognition: a cross-sectional study conducted in an urban, South Indian cohort.","authors":"Anjana J Menon, Monisha Selva, G Sandhya, Sadhana Singh, M L Abhishek, Albert Stezin, Jonas S Sundarakumar, Latha Diwakar, Thomas Gregor Issac","doi":"10.1007/s00592-025-02483-6","DOIUrl":"https://doi.org/10.1007/s00592-025-02483-6","url":null,"abstract":"<p><strong>Background: </strong>Recent research suggests that metabolic dysregulation caused by insulin resistance (IR) can have a negative impact on cognition. Therefore, the objective of this study is to explore the role of IR as an independent metabolic risk for decreased cognitive performance.</p><p><strong>Methods: </strong>The study included 1072 non-demented participants aged 45 years and above were recruited from Tata Longitudinal Study of Aging (TLSA). Fasting insulin and blood glucose levels were collected during the baseline visit. HOMA-IR formula was used to calculate IR. Cognition was assessed using the COGNITO neuropsychological test battery. Generalized Linear Regression Model (GLM) was performed to find the relationship between IR category and COGNITO battery. The brain imaging was conducted using a 3 Tesla MRI system. The cortical volumes were acquired using Freesurfer software (v7.2.0) (Salgado et al. Arq Gastroenterol 47(2):165-169, 2010). Further, GLM analysis was performed for MRI variables.</p><p><strong>Results: </strong>The estimated general prevalence of IR in our study is 56.3%. Model 1 suggested that IR is associated with reduced auditory attention (p = 0.014), and word comprehension (p = 0.043) tasks. Model 2 and 4 showed that there is an association with IR and poorerauditory attention (p = 0.015; p = 0.012) task. However, there was no significant association found in model 3. GLM analysis for MRI indicated that IR is associated with reduced brain volumes in left hemisphere like amygdala (p = 0.0012), inferior temporal lobe (p = 0.002), lateral orbitofrontal cortex (p = 0.005), superior temporal insula (p = 0.017), middle temporal lobe (p = 0.002), entorhinal (p = 0.049), and right hemisphere brain volumes like precuneus (p = 0.025), and insula (p = 0.002).</p><p><strong>Conclusions: </strong>Our study findings conclude IR is significantly associated with poorer cognitive performance related to auditory attention. Furthermore, the study also revealed that IR is associated with decreased brain volumes in specific regions.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623119","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}
Yao Huang, Wuping Liu, Ge Song, Sheng Wu, Xuejun Li, Guiping Shen, Jianghua Feng
{"title":"Metabolomic analyses of multiple biologic matrices reveal metabolic heterogeneity in diabetic complications.","authors":"Yao Huang, Wuping Liu, Ge Song, Sheng Wu, Xuejun Li, Guiping Shen, Jianghua Feng","doi":"10.1007/s00592-025-02481-8","DOIUrl":"https://doi.org/10.1007/s00592-025-02481-8","url":null,"abstract":"<p><strong>Aims: </strong>Type 2 diabetes mellitus (T2DM) arises from a complex interplay of genetic and environmental factors. Patients with T2DM are susceptible to hyperglycemia-related complications that can impair organ function, underscoring the need to explore the metabolic profiles of affected organs.</p><p><strong>Methods: </strong>In this study, a comprehensive metabolomic analysis was conducted on the serum, kidney, and heart tissues from a rat model of diabetic complications (DC). Pattern recognition and multivariate statistical analyses were applied to identify the potential biomarkers of DC, and metabolic network analysis served to understand the specific metabolic pathways associated with DC.</p><p><strong>Results: </strong>Fourteen significantly altered metabolites were identified in serum, 20 in the kidney, and 14 in the heart. The corresponding metabolic pathways included mineral absorption, mTOR signaling pathway, taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, ABC transporters, glucagon signaling pathway, protein degradation and uptake, galactose metabolism, purine metabolism, nicotinic acid and nicotinamide metabolism, and glycolysis and gluconeogenesis. Differential metabolite network analysis revealed instinct metabolic patterns among the serum, kidney, and heart. Notably, the serum's metabolic correlation patterns were found to be somewhat similar to those observed in the kidney, whereas the heart exhibited less pronounced metabolite correlations compared to the other two biological matrices.</p><p><strong>Conclusions: </strong>These findings provide insights into the mechanism underlying the development of diabetic complications. The integration of metabolomics and biological network analyses into diabetes research can potentially revolutionize the field by revealing novel biomarkers for early detection and personalized treatment of diabetes and its associated complications.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623117","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}
Huan-Huan Liu, Fan Yang, Lei Zhang, Xiao-Lu Zhang, Ning Zhao, Zhen-Ye Zhang, Jia-Bin Zhou, Tian-Peng Wei, Ling-Ling Qian, Li-Gang Ding, Ru-Xing Wang
{"title":"Decreased PLK2 promotes atrial fibrillation in diabetic mice through Nrf2/HO-1 pathway.","authors":"Huan-Huan Liu, Fan Yang, Lei Zhang, Xiao-Lu Zhang, Ning Zhao, Zhen-Ye Zhang, Jia-Bin Zhou, Tian-Peng Wei, Ling-Ling Qian, Li-Gang Ding, Ru-Xing Wang","doi":"10.1007/s00592-025-02480-9","DOIUrl":"https://doi.org/10.1007/s00592-025-02480-9","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is associated with an increased incidence of atrial fibrillation (AF). However, the exact mechanisms involved have not yet been fully elucidated. Dysregulation of cardiac potassium channels can trigger AF. This study aimed to investigate the mechanisms of abnormal expression of atrial potassium channel proteins Kv1.5, Kv4.2, and Kv4.3 in type 2 diabetic mice.</p><p><strong>Methods: </strong>The db/db mice and their control littermates were set as the T2DM group and the control (Con) group. Acetylcholine-calcium chloride was injected via the tail veins to induce AF. HL-1 cells were cultured with normal or high-glucose medium and treated with or without Dimethyl Fumarate (DMF) or hemin in vitro. The expression and cellular localization of proteins were evaluated by western blotting and immunofluorescence.</p><p><strong>Results: </strong>The results showed that high glucose impaired the expression of Kv1.5, Kv4.2 and Kv4.3 proteins both in vivo and in vitro, in parallel with a significant down-regulation of polo-like kinase 2 (PLK2), nuclear factor erythroid 2-related factor 2 (Nrf2), p-Nrf2 and heme oxygenase-1 (HO-1) proteins. Moreover, immunofluorescence revealed that both high glucose and PLK2 knockdown could result in reduced Nrf2 and p-Nrf2 expression and subsequent nuclear translocation. While overexpression of PLK2, treatment with DMF, an agonist of Nrf2, or hemin, an inducer of HO-1, could restore the reduction of Kv1.5, Kv4.2 and Kv4.3 proteins caused by high glucose.</p><p><strong>Conclusion: </strong>Diabetes reduces the expression of Kv1.5, Kv4.2 and Kv4.3 proteins in atrial cells through inhibition of PLK2/Nrf2/HO-1 pathway, thereby leading to the increased susceptibility to AF in T2DM.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623116","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}
Marina Epriliawati, Dicky L Tahapary, Indah Suci Widyahening, Anitawati Seman, Diana Gunawan, Lyra Puspa, Sukamto Koesnoe, Lilik Fauziyah, Sudarsono, Cut Neubi Getha, Ida Ayu Kshanti, Em Yunir, Tri Juli Edi Tarigan, Pradana Soewondo
{"title":"The impact of health coaching on glycemic control among uncontrolled type 2 diabetes mellitus patients: a randomized controlled trial.","authors":"Marina Epriliawati, Dicky L Tahapary, Indah Suci Widyahening, Anitawati Seman, Diana Gunawan, Lyra Puspa, Sukamto Koesnoe, Lilik Fauziyah, Sudarsono, Cut Neubi Getha, Ida Ayu Kshanti, Em Yunir, Tri Juli Edi Tarigan, Pradana Soewondo","doi":"10.1007/s00592-025-02470-x","DOIUrl":"https://doi.org/10.1007/s00592-025-02470-x","url":null,"abstract":"<p><strong>Objectives: </strong>Health coaching is a potential approach to increase glycemic control by improving diabetes patients' lifestyles. Our study aims to evaluate the impact of health coaching on glycemic control and patients' lifestyle among uncontrolled diabetes patients in Indonesia.</p><p><strong>Methods: </strong>Our study involved 60 uncontrolled T2DM (type 2 diabetes mellitus) patients with HbA1c > 7.5% from two referral hospitals in Jakarta, Indonesia. The control group received T2DM treatment and 12 standardized diabetes education, while the intervention group received an additional 12 personal health coaching sessions. The primary outcome of this study was glycemic control, which was evaluated at baseline, 3rd month, and 6th months after the intervention. Secondary outcomes included diet and physical activities as lifestyle parameters.</p><p><strong>Results: </strong>Our study showed fasting plasma glucose was significantly lower in the intervention group than in the control group (135.46 [38.61] mg/dL vs. 176.59 [62.45] mg/dL, p = 0.006). Moreover, 2-hours Post Prandial Glucose (2hPPG) was also significantly lower in the intervention group (141.42 [53.06] mg/dL vs. 242.11 [117.24] mg/dL, p < 0.001). HbA1c levels had lower values in the intervention group, although it was not significant (7.83% [2.18] vs. 8.87% [2.10], p = 0.054). No significant differences were observed for dietary control and physical activity.</p><p><strong>Conclusions: </strong>At the six-month follow-up, the health coaching program significantly improved the participants' glycemic control (FPG and 2hPPG). In addition to current diabetes care standards, the health coaching method can raise patient awareness, encourage self-care, and improve their ideal glycemic levels.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565749","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}
Marina Valenzano, Louis Massari, Paolo Abrate, Elisa Marinazzo, Stefano Allasia, Valentina Gatto, Elena Zinetti, Riccardo Fornengo
{"title":"Four-year use of SGLT2i as adjunctive therapy in adults with type 1 diabetes: a real-world experience","authors":"Marina Valenzano, Louis Massari, Paolo Abrate, Elisa Marinazzo, Stefano Allasia, Valentina Gatto, Elena Zinetti, Riccardo Fornengo","doi":"10.1007/s00592-025-02474-7","DOIUrl":"10.1007/s00592-025-02474-7","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":"62 4","pages":"575 - 578"},"PeriodicalIF":3.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522455","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}
Sunita M C De Sousa, Jennifer M N Phan, Amanda Wells, Kathy H C Wu, Hamish S Scott
{"title":"Correction: Improving detection of monogenic diabetes through reanalysis of GCK variants of uncertain significance.","authors":"Sunita M C De Sousa, Jennifer M N Phan, Amanda Wells, Kathy H C Wu, Hamish S Scott","doi":"10.1007/s00592-025-02467-6","DOIUrl":"https://doi.org/10.1007/s00592-025-02467-6","url":null,"abstract":"","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514323","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}
Daniela Sansone, Francesca Garino, Cristina Gottero, Carlotta Gauna, Alessandra Clerico, Ginevra Corneli, Fabiana Di Noi, Alessandra Rita Mainolfi, Claudio Rossi, Lisa Marafetti, Cristina Matteoda, Marcella Libera Balbo, Giuliana Petraroli, Nadia Bonelli, Claudia Chiara M Toscano, Licia Visconti, Salvatore Oleandri
{"title":"Long-term efficacy of daily oral semaglutide as add-on or switch therapy in adults with type 2 diabetes: a 12-month real-world retrospective study.","authors":"Daniela Sansone, Francesca Garino, Cristina Gottero, Carlotta Gauna, Alessandra Clerico, Ginevra Corneli, Fabiana Di Noi, Alessandra Rita Mainolfi, Claudio Rossi, Lisa Marafetti, Cristina Matteoda, Marcella Libera Balbo, Giuliana Petraroli, Nadia Bonelli, Claudia Chiara M Toscano, Licia Visconti, Salvatore Oleandri","doi":"10.1007/s00592-025-02475-6","DOIUrl":"https://doi.org/10.1007/s00592-025-02475-6","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the efficacy of oral semaglutide, either as an add-on or replacement therapy, in improving glycemic control, body weight, and cardiovascular parameters in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>This real-world study evaluated changes in glycated hemoglobin (HbA1c), body weight, and parameters of cardiovascular risk from baseline to a 12-month follow-up visit. The primary endpoint was the change in HbA1c between baseline and follow-up. Secondary endpoints included changes in body weight, the proportion of patients achieving HbA1c ≤ 7%, and combined reductions in HbA1c (≥ 1%) and body weight (≥ 5%). Exploratory endpoints were evaluated as well.</p><p><strong>Results: </strong>Data from 950 patients, predominantly female (63.7%) and with a mean age of 68.3 ± 10.1 years, were included in the study. Prior to starting semaglutide, most patients were on sulfonylureas, either as monotherapy or in combination with metformin or basal insulin. At baseline, mean HbA1c was 8.0 ± 1.3% (64.0 ± 14.2 mmol/mol), and body weight was 82.5 kg. Following 12 months of oral semaglutide treatment, HbA1c decreased significantly of -0.84% (p < 0.001) and 53% of patients achieved HbA1c ≤ 7%. HbA1c reductions were influenced by baseline levels and patient's age. Body weight decreased by 2.28 kg (p < 0.001) and 18.4% of patients achieved both ≥ 1% reduction in HbA1c and ≥ 5% in body weight. Diastolic blood pressure and LDL levels decreased significantly (p < 0.001), while systolic blood pressure and eGFR remained stable.</p><p><strong>Conclusions: </strong>When used as an add-on or replacement therapy, oral semaglutide significantly improves glycemic control, body weight, renal and cardiovascular risk factors in T2DM patients.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514325","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}
Shan-Fen Lan, Zhen-Hua Yang, Li Feng, Yu-Ting Wen, Kun-Ni Chen, Lang-Lin Fan, Ming-Jun Wang, Wen-Ting Liu
{"title":"MTDH inhibits CrAT to promote mitochondrial damage in palmitic acid-induced renal tubular cells.","authors":"Shan-Fen Lan, Zhen-Hua Yang, Li Feng, Yu-Ting Wen, Kun-Ni Chen, Lang-Lin Fan, Ming-Jun Wang, Wen-Ting Liu","doi":"10.1007/s00592-025-02476-5","DOIUrl":"https://doi.org/10.1007/s00592-025-02476-5","url":null,"abstract":"<p><strong>Purpose: </strong>Mitochondrial dysfunction leading to impaired energy metabolism has been recognized as a pivotal factor contributing to renal tubular epithelial cells (RTECs) damage in the context of dyslipidemia conditions in diabetic kidney disease (DKD). The primary objective of this study is to elucidate the role and underlying mechanism of the proto-oncogene Metadherin (MTDH) in mediating mitochondrial damage within this specific pathological context in vitro.</p><p><strong>Methods: </strong>The expression of MTDH in RTECs was modulated by transfecting small interfering RNA and plasmid, while palmitic acid (PA) was employed to simulate diabetic lipid metabolism disorder. Mitochondrial damage was evaluated by examining various parameters including mitochondrial morphology, membrane potential, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) production, as well as morphological and structural alterations. Additionally, Carnitine acetyltransferase (CrAT) expression was assessed using Western blotting and quantitative real-time polymerase chain reaction, and CrAT activity was quantified.</p><p><strong>Result: </strong>MTDH expression was upregulated in PA-induced RTECs, while CrAT expression and activity were inhibited. Downregulation of MTDH mitigated PA-induced mitochondrial damage, as demonstrated by the preservation of mitochondrial membrane potential, reduction in mitochondrial ROS production, prevention of ATP depletion, and maintenance of mitochondrial structure. This was accompanied by an upregulation in CrAT expression and activity. Conversely, overexpression of MTDH exacerbated mitochondrial dysfunction by impairing membrane potential, augmenting mitochondrial ROS production, inhibiting ATP synthesis, and suppressing CrAT expression and activity.</p><p><strong>Conclusion: </strong>In the context of dyslipidemia conditions, MTDH is upregulated and suppresses the expression and activity of CrAT in RTECs, thereby inducing mitochondrial dysfunction and perturbing energy metabolism. These alterations exacerbate the injury to RTECs, consequently promoting the progression of DKD.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655789","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}