Jiajun Wu, Shuyan Zhang, Lin Mu, Zhi-Guo Dong, Yin-Jian Zhang
BACKGROUND Diabetic retinopathy (DR) is the primary cause of visual problems in patients with diabetes. The Heyingwuzi formulation (HYWZF) is effective against DR. AIM To determine the HYWZF prevention mechanisms, especially those underlying mitophagy. METHODS Human retinal capillary endothelial cells (HRCECs) were treated with high glucose (hg), HYWZF serum, PX-478, or Mdivi-1 in vitro . Then, cell counting kit-8, transwell, and tube formation assays were used to evaluate HRCEC proliferation, invasion, and tube formation, respectively. Transmission electron microscopy was used to assess mitochondrial morphology, and Western blotting was used to determine the protein levels. Flow cytometry was used to assess cell apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Moreover, C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks. Blood glucose levels and body weight were monitored continuously. Changes in retinal characteristics were evaluated using hematoxylin and eosin, tar violet, and periodic acid-Schiff staining. Protein levels in retinal tissues were determined via Western blotting, immunohistochemistry, and immunostaining. RESULTS HYWZF inhibited excessive ROS production, apoptosis, tube formation, and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro . It increased the mRNA expression levels of BCL2-interacting protein 3 (BNIP3 ), FUN14 domain-containing 1, BNIP3-like (BNIP3L , also known as NIX ), PARKIN , PTEN-induced kinase 1, and hypoxia-inducible factor (HIF )-1α . Moreover, it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio. However, PX-478 and Mdivi-1 reversed these effects. Additionally, PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy. HYWZF intervention improved the symptoms of diabetes, tissue damage, number of acellular capillaries, and oxidative stress in vivo . Furthermore, in vivo experiments confirmed the results of in vitro experiments. CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.
{"title":"Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis","authors":"Jiajun Wu, Shuyan Zhang, Lin Mu, Zhi-Guo Dong, Yin-Jian Zhang","doi":"10.4239/wjd.v15.i6.1317","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1317","url":null,"abstract":"BACKGROUND\u0000 Diabetic retinopathy (DR) is the primary cause of visual problems in patients with diabetes. The Heyingwuzi formulation (HYWZF) is effective against DR.\u0000 AIM\u0000 To determine the HYWZF prevention mechanisms, especially those underlying mitophagy.\u0000 METHODS\u0000 Human retinal capillary endothelial cells (HRCECs) were treated with high glucose (hg), HYWZF serum, PX-478, or Mdivi-1 in vitro . Then, cell counting kit-8, transwell, and tube formation assays were used to evaluate HRCEC proliferation, invasion, and tube formation, respectively. Transmission electron microscopy was used to assess mitochondrial morphology, and Western blotting was used to determine the protein levels. Flow cytometry was used to assess cell apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential. Moreover, C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks. Blood glucose levels and body weight were monitored continuously. Changes in retinal characteristics were evaluated using hematoxylin and eosin, tar violet, and periodic acid-Schiff staining. Protein levels in retinal tissues were determined via Western blotting, immunohistochemistry, and immunostaining.\u0000 RESULTS\u0000 HYWZF inhibited excessive ROS production, apoptosis, tube formation, and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro . It increased the mRNA expression levels of BCL2-interacting protein 3 (BNIP3 ), FUN14 domain-containing 1, BNIP3-like (BNIP3L , also known as NIX ), PARKIN , PTEN-induced kinase 1, and hypoxia-inducible factor (HIF )-1α . Moreover, it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio. However, PX-478 and Mdivi-1 reversed these effects. Additionally, PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy. HYWZF intervention improved the symptoms of diabetes, tissue damage, number of acellular capillaries, and oxidative stress in vivo . Furthermore, in vivo experiments confirmed the results of in vitro experiments.\u0000 CONCLUSION\u0000 HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141337703","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}
In this editorial, we commented on the article published in the recent issue of the World Journal of Diabetes . Diabetic cardiomyopathy (DCM) is characterized by myocardial fibrosis, ventricular hypertrophy and diastolic dysfunction in diabetic patients, which can cause heart failure and threaten the life of patients. The pathogenesis of DCM has not been fully clarified, and it may involve oxidative stress, inflammatory stimulation, apoptosis, and autophagy. There is lack of effective therapies for DCM in the clinical practice. Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques, and exhibit definite cardiovascular protective effects. Studies have shown that statins also have anti-inflammatory and antioxidant effects. We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and anti-inflammatory effects of macrophage polarization on diabetic myocardium, and thereby improving DCM.
{"title":"Atorvastatin ameliorated myocardial fibrosis by inhibiting oxidative stress and modulating macrophage polarization in diabetic cardiomyopathy","authors":"Xiao-Tian Lei, Dan-Lan Pu, Geng Shan, Qi-Nan Wu","doi":"10.4239/wjd.v15.i6.1070","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1070","url":null,"abstract":"In this editorial, we commented on the article published in the recent issue of the World Journal of Diabetes . Diabetic cardiomyopathy (DCM) is characterized by myocardial fibrosis, ventricular hypertrophy and diastolic dysfunction in diabetic patients, which can cause heart failure and threaten the life of patients. The pathogenesis of DCM has not been fully clarified, and it may involve oxidative stress, inflammatory stimulation, apoptosis, and autophagy. There is lack of effective therapies for DCM in the clinical practice. Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques, and exhibit definite cardiovascular protective effects. Studies have shown that statins also have anti-inflammatory and antioxidant effects. We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and anti-inflammatory effects of macrophage polarization on diabetic myocardium, and thereby improving DCM.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141337766","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}
Le-Yang Li, Song-Mei Li, Bo-Xian Pang, Jun-Ping Wei, Qiu-Hong Wang
BACKGROUND Obesity in children and adolescents is a serious problem, and the efficacy of exercise therapy for these patients is controversial. AIM To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers. METHODS The PubMed, Web of Science, and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023. The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children. RESULTS In total, 1010 patients from 28 studies were included. Exercise therapy reduced the levels of fasting blood glucose (FBG) [standardized mean difference (SMD): -0.78; 95% confidence interval (CI): -1.24 to -0.32, P = 0.0008], fasting insulin (FINS) (SMD: -1.55; 95%CI: -2.12 to -0.98, P < 0.00001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD: -1.58; 95%CI: -2.20 to -0.97, P < 0.00001), interleukin-6 (IL-6) (SMD: -1.31; 95%CI: -2.07 to -0.55, P = 0.0007), C-reactive protein (CRP) (SMD: -0.64; 95%CI: -1.21 to -0.08, P = 0.03), and leptin (SMD: -3.43; 95%CI: -5.82 to -1.05, P = 0.005) in overweight and obese children. Exercise training increased adiponectin levels (SMD: 1.24; 95%CI: 0.30 to 2.18, P = 0.01) but did not improve tumor necrosis factor-alpha (TNF-α) levels (SMD: -0.80; 95%CI: -1.77 to 0.18, P = 0.11). CONCLUSION In summary, exercise therapy improves glucose metabolism by reducing levels of FBG, FINS, HOMA-IR, as well as improves inflammatory status by reducing levels of IL-6, CRP, leptin, and increasing levels of adiponectin in overweight and obese children. There was no statistically significant effect between exercise training and levels of TNF-α. Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.
{"title":"Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents: A meta-analysis","authors":"Le-Yang Li, Song-Mei Li, Bo-Xian Pang, Jun-Ping Wei, Qiu-Hong Wang","doi":"10.4239/wjd.v15.i6.1353","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1353","url":null,"abstract":"BACKGROUND\u0000 Obesity in children and adolescents is a serious problem, and the efficacy of exercise therapy for these patients is controversial.\u0000 AIM\u0000 To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers.\u0000 METHODS\u0000 The PubMed, Web of Science, and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023. The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children.\u0000 RESULTS\u0000 In total, 1010 patients from 28 studies were included. Exercise therapy reduced the levels of fasting blood glucose (FBG) [standardized mean difference (SMD): -0.78; 95% confidence interval (CI): -1.24 to -0.32, P = 0.0008], fasting insulin (FINS) (SMD: -1.55; 95%CI: -2.12 to -0.98, P < 0.00001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD: -1.58; 95%CI: -2.20 to -0.97, P < 0.00001), interleukin-6 (IL-6) (SMD: -1.31; 95%CI: -2.07 to -0.55, P = 0.0007), C-reactive protein (CRP) (SMD: -0.64; 95%CI: -1.21 to -0.08, P = 0.03), and leptin (SMD: -3.43; 95%CI: -5.82 to -1.05, P = 0.005) in overweight and obese children. Exercise training increased adiponectin levels (SMD: 1.24; 95%CI: 0.30 to 2.18, P = 0.01) but did not improve tumor necrosis factor-alpha (TNF-α) levels (SMD: -0.80; 95%CI: -1.77 to 0.18, P = 0.11).\u0000 CONCLUSION\u0000 In summary, exercise therapy improves glucose metabolism by reducing levels of FBG, FINS, HOMA-IR, as well as improves inflammatory status by reducing levels of IL-6, CRP, leptin, and increasing levels of adiponectin in overweight and obese children. There was no statistically significant effect between exercise training and levels of TNF-α. Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141335987","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}
BACKGROUND Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies. AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism. METHODS To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1). RESULTS In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR. CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.
背景 灵桂术甘汤是一种广泛使用的经典中药配方，最近在动物实验中被证明可改善高脂饮食（HFD）诱导的胰岛素抵抗（IR）。目的 评估 LGZG 水煎剂对高脂饮食诱导的 IR 的治疗效果，并探索其潜在的内在机制。方法 为了建立 IR 大鼠模型，先给予 12 周高密度脂蛋白膳食，然后用 LGZG 治疗 4 周。通过生化测试和口服葡萄糖耐量测试来确定 IR 状态。使用靶向元生物组学平台分析血清代谢物的变化，使用定量实时 PCR (qRT-PCR) 评估核糖体蛋白 S6 激酶 beta 1 (S6K1) 的基因表达。结果 在 IR 大鼠中，LGZG 可降低体重和肝脏脂肪变性指数。它能有效控制血糖和食物摄入量，同时保护胰岛细胞。代谢物分析表明，HFD 组和 HFD-LGZG 组之间存在显著差异。LGZG干预降低了支链氨基酸水平。色氨酸、丙氨酸、牛磺酸和天冬酰胺等与IR相关的代谢物水平显著下降。正如 qRT-PCR 所示，由于 S6K1 的表达同时增加，IR 可能与氨基酸有关。结论 我们的研究有力地表明，LGZG 水煎剂可降低 HFD 诱导的 IR。LGZG 可通过代谢途径激活 S6K1。这些发现为 LGZG 治疗 IR 的潜力奠定了基础。
{"title":"Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance","authors":"Xiao-Ming Liu, Shi-Qing Yuan, Ying-Yuan Ning, Shi-Jia Nie, Xu-Qiong Wang, Hong-Yi Jia, Xiu-Li Zheng","doi":"10.4239/wjd.v15.i6.1291","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1291","url":null,"abstract":"BACKGROUND\u0000 Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies.\u0000 AIM\u0000 To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.\u0000 METHODS\u0000 To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1).\u0000 RESULTS\u0000 In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR.\u0000 CONCLUSIONS\u0000 Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141336683","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}
Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.
二甲双胍是一种常见的糖尿病药物，可通过抑制线粒体氧化磷酸化而降低乳酸清除率，从而导致二甲双胍相关性乳酸酸中毒（MALA）。由于糖尿病是重症患者中常见的慢性代谢性疾病，因此在重症监护室或高依赖性病房收治的重症患者中经常会发现他们在使用二甲双胍之前就已经存在糖尿病。因此，这篇微型综述旨在向临床医生提供有关 MALA 的最新信息，并为其诊断和治疗提供实用方法。接受二甲双胍治疗并出现高阴离子间隙代谢性酸中毒的重症患者可能会被怀疑患有MALA，当乳酸超过5 mmol/L时即可确诊。风险因素包括减少二甲双胍肾脏排泄的因素（任何原因引起的肾功能损害、组胺-2 受体拮抗剂、利博昔单抗）和过度饮酒（因为乙醇氧化会消耗烟酰胺腺嘌呤二核苷酸，而烟酰胺腺嘌呤二核苷酸也是乳酸盐代谢所必需的）。MALA 的治疗包括立即停用二甲双胍、支持性治疗、治疗其他并发乳酸酸中毒的原因（如败血症）以及治疗任何并存的糖尿病酮症酸中毒。严重的 MALA 需要通过间歇性血液透析或持续性肾脏替代疗法在体外清除二甲双胍。重新开始服用二甲双胍的最佳时间尚未得到充分研究。但合理的做法是，首先确保乳酸酸中毒已经缓解，然后在危重病人康复后重新检查肾功能，确保肾小球滤过率达到或优于 30 mL/min/1.73 m2，然后再重新开始服用二甲双胍。
{"title":"Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients","authors":"Kay Choong See","doi":"10.4239/wjd.v15.i6.1178","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1178","url":null,"abstract":"Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141336793","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}
Alessia Annicchiarico, Barbara Barile, C. Buccoliero, G. P. Nicchia, Giacomina Brunetti
Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic β cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated. The first approaches included enhancing endogenous β cell activity or transplanting new islets. The protocol for this kind of intervention has recently been optimized, leading to standardized procedures. It is indicated for diabetic patients with severe hypoglycemia, complicated by impaired hypoglycemia awareness or exacerbated glycemic lability. Transplantation has been associated with improvement in all comorbidities associated with diabetes, quality of life, and survival. However, different trials are ongoing to further improve the beneficial effects of transplantation. Furthermore, to overcome some limitations associated with the availability of islets/pancreas, alternative therapeutic strategies are under evaluation, such as the use of mesenchymal stem cells (MSCs) or induced pluripotent stem cells for transplantation. The cotransplantation of MSCs with islets has been successful, thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms, including exosome release. The use of induced pluripotent stem cells is recent and requires further investigation. The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities, such as wound healing. Despite the number of advantages of the direct injection of MSCs, new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results. In conclusion, this paper offered an overview of new alternative strategies for diabetes management while highlighting some limitations that will need to be overcome by future approaches.
{"title":"Alternative therapeutic strategies in diabetes management","authors":"Alessia Annicchiarico, Barbara Barile, C. Buccoliero, G. P. Nicchia, Giacomina Brunetti","doi":"10.4239/wjd.v15.i6.1142","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1142","url":null,"abstract":"Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic β cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated. The first approaches included enhancing endogenous β cell activity or transplanting new islets. The protocol for this kind of intervention has recently been optimized, leading to standardized procedures. It is indicated for diabetic patients with severe hypoglycemia, complicated by impaired hypoglycemia awareness or exacerbated glycemic lability. Transplantation has been associated with improvement in all comorbidities associated with diabetes, quality of life, and survival. However, different trials are ongoing to further improve the beneficial effects of transplantation. Furthermore, to overcome some limitations associated with the availability of islets/pancreas, alternative therapeutic strategies are under evaluation, such as the use of mesenchymal stem cells (MSCs) or induced pluripotent stem cells for transplantation. The cotransplantation of MSCs with islets has been successful, thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms, including exosome release. The use of induced pluripotent stem cells is recent and requires further investigation. The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities, such as wound healing. Despite the number of advantages of the direct injection of MSCs, new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results. In conclusion, this paper offered an overview of new alternative strategies for diabetes management while highlighting some limitations that will need to be overcome by future approaches.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141337208","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}
Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes. Of particular interest, age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.
{"title":"Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes","authors":"Chaeyoung Lee","doi":"10.4239/wjd.v15.i6.1381","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1381","url":null,"abstract":"Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes. Of particular interest, age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141337429","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}
Jun-Ling Li, Jin Zhao, Zhen-Feng Guo, Chang Xiao, Xuan Liu
BACKGROUND Dry eye syndrome (DES) after diabetic cataract surgery can seriously affect the patient’s quality of life. Therefore, effective alleviation of symptoms in patients with this disease has important clinical significance. AIM To explore the clinical effect of recombinant human epidermal growth factor (rhEGF) plus sodium hyaluronate (SH) eye drops on DES after cataract surgery in patients with diabetes. METHODS We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital, Affiliated Hospital of Nankai University between April 2021 and April 2023. They were classified into an observation group (42 cases, rhEGF + SH eye drops) and a control group (40 cases, SH eye drops alone), depending on the different treatment schemes. The thera-peutic efficacy, dry eye symptom score, tear film breakup time (TFBUT), basic tear secretion score [assessed using Schirmer I test (SIt)], corneal fluorescein staining (FL) score, tear inflammatory markers, adverse reactions during treatment, and treatment satisfaction were compared between the two groups. RESULTS Therapeutic efficacy was higher in the observation group compared with the control group. Both groups showed improved TFBUT and dry eye, as well as improved SIt and FL scores after treatment, with a more pronounced improvement in the observation group. Although no marked differences in adverse reactions were observed between the two groups, treatment satisfaction was higher in the observation group. CONCLUSION rhEGF + SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy, fewer adverse reactions, and high safety levels. Thus, this treatment should be promoted in clinical practice.
背景糖尿病白内障术后干眼症（DES）会严重影响患者的生活质量。因此，有效缓解该病患者的症状具有重要的临床意义。目的 探讨重组人表皮生长因子（rhEGF）加透明质酸钠（SH）滴眼液对糖尿病患者白内障术后干眼症的临床效果。方法 我们对 2021 年 4 月至 2023 年 4 月期间在南开大学附属天津北辰医院接受白内障手术后发生 DES 的 82 例糖尿病患者进行了回顾性评估。根据不同的治疗方案，他们被分为观察组（42 例，rhEGF + SH 滴眼液）和对照组（40 例，单用 SH 滴眼液）。比较两组的疗效、干眼症状评分、泪膜破裂时间（TFBUT）、基本泪液分泌评分[使用 Schirmer I 试验（SIt）评估]、角膜荧光素染色（FL）评分、泪液炎症标志物、治疗期间的不良反应以及治疗满意度。结果 观察组的疗效高于对照组。两组治疗后 TFBUT 和干眼症均有所改善，SIt 和 FL 评分也有所提高，其中观察组的改善更为明显。虽然两组在不良反应方面没有明显差异，但观察组的治疗满意度更高。结论 rhEGF + SH 滴眼液能有效改善干眼症和视力障碍，疗效好，不良反应少，安全性高，给患者带来了临床益处。因此，这种治疗方法应在临床实践中推广。
{"title":"Efficacy of recombinant human epidermal growth factor plus sodium hyaluronate eye drops in diabetic dry eye post-cataract surgery","authors":"Jun-Ling Li, Jin Zhao, Zhen-Feng Guo, Chang Xiao, Xuan Liu","doi":"10.4239/wjd.v15.i6.1234","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1234","url":null,"abstract":"BACKGROUND\u0000 Dry eye syndrome (DES) after diabetic cataract surgery can seriously affect the patient’s quality of life. Therefore, effective alleviation of symptoms in patients with this disease has important clinical significance.\u0000 AIM\u0000 To explore the clinical effect of recombinant human epidermal growth factor (rhEGF) plus sodium hyaluronate (SH) eye drops on DES after cataract surgery in patients with diabetes.\u0000 METHODS\u0000 We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital, Affiliated Hospital of Nankai University between April 2021 and April 2023. They were classified into an observation group (42 cases, rhEGF + SH eye drops) and a control group (40 cases, SH eye drops alone), depending on the different treatment schemes. The thera-peutic efficacy, dry eye symptom score, tear film breakup time (TFBUT), basic tear secretion score [assessed using Schirmer I test (SIt)], corneal fluorescein staining (FL) score, tear inflammatory markers, adverse reactions during treatment, and treatment satisfaction were compared between the two groups.\u0000 RESULTS\u0000 Therapeutic efficacy was higher in the observation group compared with the control group. Both groups showed improved TFBUT and dry eye, as well as improved SIt and FL scores after treatment, with a more pronounced improvement in the observation group. Although no marked differences in adverse reactions were observed between the two groups, treatment satisfaction was higher in the observation group.\u0000 CONCLUSION\u0000 rhEGF + SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy, fewer adverse reactions, and high safety levels. Thus, this treatment should be promoted in clinical practice.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141336190","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}
Zi-Tian Liu, Guangwei Yang, Xiang Zhao, Shuo-Hui Dong, Yang Jiao, Zheng Ge, Ao Yu, Xiqiang Zhang, Xinzhen Xu, Zhi-Qiang Cheng, Xiang Zhang, Kexin Wang
BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.
{"title":"Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion","authors":"Zi-Tian Liu, Guangwei Yang, Xiang Zhao, Shuo-Hui Dong, Yang Jiao, Zheng Ge, Ao Yu, Xiqiang Zhang, Xinzhen Xu, Zhi-Qiang Cheng, Xiang Zhang, Kexin Wang","doi":"10.4239/wjd.v15.i6.1340","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1340","url":null,"abstract":"BACKGROUND\u0000 The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear.\u0000 AIM\u0000 To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.\u0000 METHODS\u0000 DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence.\u0000 RESULTS\u0000 After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.\u0000 CONCLUSION\u0000 GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141337199","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}
Xiangyu Gao, Chen-Xia Zhou, Hong-Mei Li, Min Cheng, Da Chen, Zi-Yi Li, Bo Feng, Jun Song
BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-β was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.
{"title":"Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes","authors":"Xiangyu Gao, Chen-Xia Zhou, Hong-Mei Li, Min Cheng, Da Chen, Zi-Yi Li, Bo Feng, Jun Song","doi":"10.4239/wjd.v15.i6.1263","DOIUrl":"https://doi.org/10.4239/wjd.v15.i6.1263","url":null,"abstract":"BACKGROUND\u0000 Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM).\u0000 AIM\u0000 To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels.\u0000 METHODS\u0000 A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.\u0000 RESULTS\u0000 The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-β was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control.\u0000 CONCLUSION\u0000 The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141337358","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}
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