BACKGROUND Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1β and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.
{"title":"Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling","authors":"Huaijie Wang, Li-Bin Zhang, Si-Peng Sun, Qingtao Yan, Zhi-Qin Gao, Fang-Ming Fu, Mei-Hua Qu","doi":"10.4239/wjd.v15.i2.287","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.287","url":null,"abstract":"BACKGROUND\u0000 Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear.\u0000 AIM\u0000 To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.\u0000 METHODS\u0000 A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence.\u0000 RESULTS\u0000 Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1β and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats.\u0000 CONCLUSION\u0000 DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"189 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139834802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND Helicobacter pylori (H. pylori ) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown. AIM To explore potential molecular connections between H. pylori infection and T2DM. METHODS We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed. RESULTS A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4 , ITGAM , C5AR1 , FCER1G , and FCGR2A , were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes. CONCLUSION We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori -induced onset of T2DM.
{"title":"Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus: A pilot bioinformatics study","authors":"Han Chen, Guo-Xin Zhang, Xiao-Ying Zhou","doi":"10.4239/wjd.v15.i2.170","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.170","url":null,"abstract":"BACKGROUND\u0000 Helicobacter pylori (H. pylori ) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown.\u0000 AIM\u0000 To explore potential molecular connections between H. pylori infection and T2DM.\u0000 METHODS\u0000 We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed.\u0000 RESULTS\u0000 A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4 , ITGAM , C5AR1 , FCER1G , and FCGR2A , were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes.\u0000 CONCLUSION\u0000 We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori -induced onset of T2DM.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"396 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139834948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Gonzalez, Cristian Lindner, Ivan Schneider, Erik Diaz, Miguel Angel Morales, Armando Rojas
Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage T2DM is widely documented. These dietary compounds exert their beneficial effects through several actions, including the protection of pancreatic islet β-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorate diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.
{"title":"Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus","authors":"I. Gonzalez, Cristian Lindner, Ivan Schneider, Erik Diaz, Miguel Angel Morales, Armando Rojas","doi":"10.4239/wjd.v15.i2.154","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.154","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage T2DM is widely documented. These dietary compounds exert their beneficial effects through several actions, including the protection of pancreatic islet β-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorate diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"113 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139836385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations. AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain. METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored. RESULTS A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient’s clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect. CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.
{"title":"Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients","authors":"Ping Shi, Yang Tian, Feng Xu, Lu-Na Liu, Wanhong Wu, Ying-Zhou Shi, An-Qi Dai, Hang-Yu Fang, Kun-Xia Li, Chao Xu","doi":"10.4239/wjd.v15.i2.275","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.275","url":null,"abstract":"BACKGROUND\u0000 Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.\u0000 AIM\u0000 To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.\u0000 METHODS\u0000 Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.\u0000 RESULTS\u0000 A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient’s clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect.\u0000 CONCLUSION\u0000 This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"55 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139775501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.
{"title":"Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus","authors":"Omar Ramos-Lopez","doi":"10.4239/wjd.v15.i2.142","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.142","url":null,"abstract":"Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"133 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139836312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The global diabetes surge poses a critical public health challenge, emphasizing the need for effective glycemic control. However, rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications, necessitating a reevaluation of the speed and intensity of glycemic correction. Theories suggest swift blood sugar reductions may cause inflammation, oxidative stress, and neurovascular changes, resulting in complications. Healthcare providers should cautiously approach aggressive glycemic control, especially in long-standing, poorly controlled diabetes. Preventing and managing these complications requires a personalized, comprehensive approach with education, monitoring, and interdisciplinary care. Diabetes management must balance short and long-term goals, prioritizing overall well-being. This editorial underscores the need for a personalized, nuanced approach, focusing on equilibrium between glycemic control and avoiding overcorrection.
{"title":"Balancing act: The dilemma of rapid hyperglycemia correction in diabetes management","authors":"Ke-Xin Zhang, Cheng-Xia Kan, Xiao-Dong Sun","doi":"10.4239/wjd.v15.i2.129","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.129","url":null,"abstract":"The global diabetes surge poses a critical public health challenge, emphasizing the need for effective glycemic control. However, rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications, necessitating a reevaluation of the speed and intensity of glycemic correction. Theories suggest swift blood sugar reductions may cause inflammation, oxidative stress, and neurovascular changes, resulting in complications. Healthcare providers should cautiously approach aggressive glycemic control, especially in long-standing, poorly controlled diabetes. Preventing and managing these complications requires a personalized, comprehensive approach with education, monitoring, and interdisciplinary care. Diabetes management must balance short and long-term goals, prioritizing overall well-being. This editorial underscores the need for a personalized, nuanced approach, focusing on equilibrium between glycemic control and avoiding overcorrection.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"27 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139776120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fen Feng, Bin Zhou, Ci-La Zhou, Ping Huang, Gang Wang, Kuang Yao
BACKGROUND Diabetes and thyroiditis are closely related. They occur in combination and cause significant damage to the body. There is no clear treatment for type-2 diabetes mellitus (T2DM) with Hashimoto's thyroiditis (HT). While single symptomatic drug treatment of the two diseases is less effective, combined drug treatment may improve efficacy. AIM To investigate the effect of a combination of vitamin D, selenium, and hypo-glycemic agents in T2DM with HT. METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023. Fifty patients were assigned to the control group, test group A, and test group B according to different treatment methods. The control group received low-iodine diet guidance and hypoglycemic drug treatment. Test group A received the control treatment plus vitamin D treatment. Test group B received the group A treatment plus selenium. Blood levels of markers of thyroid function [free T3 (FT3), thyroid stimulating hormone (TSH), free T4 (FT4)], autoantibodies [thyroid peroxidase antibody (TPOAB) and thyroid globulin antibody (TGAB)], blood lipid index [low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triacylglycerol (TG)], blood glucose index [fasting blood glucose (FBG), and hemoglobin A1c (HbA1c)] were measured pre-treatment and 3 and 6 months after treatment. The relationships between serum 25-hydroxyvitamin D3 [25 (OH) D3] level and each of these indices were analyzed. RESULTS The levels of 25 (OH) D3, FT3, FT4, and LDL-C increased in the order of the control group, test group A, and test group B (all P < 0.05). The TPOAB, TGAB, TC, TG, FBG, HbA1c, and TSH levels increased in the order of test groups B, A, and the control group (all P < 0.05). All the above indices were compared after 3 and 6 months of treatment. Pre-treatment, there was no divergence in serum 25 (OH) D3 level, thyroid function-related indexes, autoantibodies level, blood glucose, and blood lipid index between the control group, test groups A and B (all P > 0.05). The 25 (OH) D3 levels in test groups A and B were negatively correlated with FT4 and TGAB (all P < 0.05). CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function, autoantibody, and blood glucose and lipid levels.
背景糖尿病和甲状腺炎密切相关。它们同时发生，会对身体造成严重损害。对于 2 型糖尿病（T2DM）合并桥本氏甲状腺炎（HT），目前还没有明确的治疗方法。虽然这两种疾病的单一对症药物治疗效果较差，但联合用药可提高疗效。目的 研究维生素 D、硒和降糖药联合治疗 T2DM 伴有桥本氏甲状腺炎的效果。方法 该回顾性研究纳入了2020年3月至2023年2月在邵阳市中心医院接受治疗的150例T2DM合并高血压患者。根据不同的治疗方法，50 名患者被分配到对照组、试验 A 组和试验 B 组。对照组接受低碘饮食指导和降糖药物治疗。试验 A 组接受对照组治疗加维生素 D 治疗。试验 B 组接受 A 组治疗加硒治疗。血液中甲状腺功能指标[游离 T3 (FT3)、促甲状腺激素 (TSH)、游离 T4 (FT4)]、自身抗体[甲状腺过氧化物酶抗体 (TPOAB) 和甲状腺球蛋白抗体 (TGAB)]的水平、血脂指数[低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、三酰甘油（TG）]、血糖指数[空腹血糖（FBG）和血红蛋白 A1c（HbA1c）]在治疗前、治疗后 3 个月和 6 个月进行测量。分析了血清 25- 羟基维生素 D3 [25 (OH) D3] 水平与上述各项指标之间的关系。结果 25 (OH) D3、FT3、FT4 和 LDL-C 的水平依次升高，对照组、试验 A 组和试验 B 组的升高幅度最大（均 P < 0.05）。TPOAB、TGAB、TC、TG、FBG、HbA1c 和 TSH 水平的升高顺序依次为 B 组、A 组和对照组（均 P <0.05）。上述所有指标在治疗 3 个月和 6 个月后进行了比较。治疗前，对照组、试验组 A 和试验组 B 的血清 25 (OH) D3 水平、甲状腺功能相关指标、自身抗体水平、血糖和血脂指标均无差异（均 P > 0.05）。试验组 A 和 B 的 25 (OH) D3 水平与 FT4 和 TGAB 呈负相关（均 P <0.05）。结论 联合用药治疗 T2DM 伴 HT 能明显改善甲状腺功能、自身抗体、血糖和血脂水平。
{"title":"Vitamin D, selenium, and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis","authors":"Fen Feng, Bin Zhou, Ci-La Zhou, Ping Huang, Gang Wang, Kuang Yao","doi":"10.4239/wjd.v15.i2.209","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.209","url":null,"abstract":"BACKGROUND\u0000 Diabetes and thyroiditis are closely related. They occur in combination and cause significant damage to the body. There is no clear treatment for type-2 diabetes mellitus (T2DM) with Hashimoto's thyroiditis (HT). While single symptomatic drug treatment of the two diseases is less effective, combined drug treatment may improve efficacy.\u0000 AIM\u0000 To investigate the effect of a combination of vitamin D, selenium, and hypo-glycemic agents in T2DM with HT.\u0000 METHODS\u0000 This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023. Fifty patients were assigned to the control group, test group A, and test group B according to different treatment methods. The control group received low-iodine diet guidance and hypoglycemic drug treatment. Test group A received the control treatment plus vitamin D treatment. Test group B received the group A treatment plus selenium. Blood levels of markers of thyroid function [free T3 (FT3), thyroid stimulating hormone (TSH), free T4 (FT4)], autoantibodies [thyroid peroxidase antibody (TPOAB) and thyroid globulin antibody (TGAB)], blood lipid index [low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triacylglycerol (TG)], blood glucose index [fasting blood glucose (FBG), and hemoglobin A1c (HbA1c)] were measured pre-treatment and 3 and 6 months after treatment. The relationships between serum 25-hydroxyvitamin D3 [25 (OH) D3] level and each of these indices were analyzed.\u0000 RESULTS\u0000 The levels of 25 (OH) D3, FT3, FT4, and LDL-C increased in the order of the control group, test group A, and test group B (all P < 0.05). The TPOAB, TGAB, TC, TG, FBG, HbA1c, and TSH levels increased in the order of test groups B, A, and the control group (all P < 0.05). All the above indices were compared after 3 and 6 months of treatment. Pre-treatment, there was no divergence in serum 25 (OH) D3 level, thyroid function-related indexes, autoantibodies level, blood glucose, and blood lipid index between the control group, test groups A and B (all P > 0.05). The 25 (OH) D3 levels in test groups A and B were negatively correlated with FT4 and TGAB (all P < 0.05).\u0000 CONCLUSION\u0000 The combination drug treatment for T2DM with HT significantly improved thyroid function, autoantibody, and blood glucose and lipid levels.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"360 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139834220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations. AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain. METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored. RESULTS A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient’s clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect. CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.
{"title":"Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients","authors":"Ping Shi, Yang Tian, Feng Xu, Lu-Na Liu, Wanhong Wu, Ying-Zhou Shi, An-Qi Dai, Hang-Yu Fang, Kun-Xia Li, Chao Xu","doi":"10.4239/wjd.v15.i2.275","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.275","url":null,"abstract":"BACKGROUND\u0000 Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.\u0000 AIM\u0000 To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.\u0000 METHODS\u0000 Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.\u0000 RESULTS\u0000 A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient’s clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect.\u0000 CONCLUSION\u0000 This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"426 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139835086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy (DN). The regulatory relationship between long noncoding RNAs (lncRNAs) and podocyte apoptosis has recently become another research hot spot in the DN field. AIM To investigate whether lncRNA protein-disulfide isomerase-associated 3 (Pdia3) could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism. METHODS Using normal glucose or high glucose (HG)-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress (ERS) were explored. LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction. Relative cell viability was detected through the cell counting kit-8 colorimetric assay. The podocyte apoptosis rate in each group was measured through flow cytometry. The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay. Finally, western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p. RESULTS The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes. Next, lncRNA Pdia3 was involved in HG-induced podocyte apoptosis. Furthermore, the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes. CONCLUSION Taken together, this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p, which might provide a potential therapeutic target for DN.
{"title":"Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p","authors":"Yin-Xi He, Ting Wang, Wen-Xian Li, Yan-Xia Chen","doi":"10.4239/wjd.v15.i2.260","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.260","url":null,"abstract":"BACKGROUND\u0000 Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy (DN). The regulatory relationship between long noncoding RNAs (lncRNAs) and podocyte apoptosis has recently become another research hot spot in the DN field.\u0000 AIM\u0000 To investigate whether lncRNA protein-disulfide isomerase-associated 3 (Pdia3) could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism.\u0000 METHODS\u0000 Using normal glucose or high glucose (HG)-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress (ERS) were explored. LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction. Relative cell viability was detected through the cell counting kit-8 colorimetric assay. The podocyte apoptosis rate in each group was measured through flow cytometry. The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay. Finally, western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p.\u0000 RESULTS\u0000 The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes. Next, lncRNA Pdia3 was involved in HG-induced podocyte apoptosis. Furthermore, the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes.\u0000 CONCLUSION\u0000 Taken together, this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p, which might provide a potential therapeutic target for DN.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"37 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139775071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuo Xie, Liping Yu, Fei Chen, Yao Wang, Ruifen Deng, Xue-Lian Zhang, Bo Zhang
BACKGROUND Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, the global burden of which is rising. It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults. To develop a focused screening plan and treatment for Chinese adults with prediabetes, it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age. AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China. METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008. A thorough evaluation was conducted. Individuals with prediabetes were categorized into two groups based on age. Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years. Random forest was established in both age groups. SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution. RESULTS In total, 6948 people were diagnosed with prediabetes in this study. In pre-diabetes, prevalences of CVD were 5 (0.29%) in the younger group and 148 (2.85%) in the older group. Overall, 11.11% of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years. In the younger age group, the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle, whereas in the older age group, resident status was more closely linked. CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes. It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.
{"title":"Age-specific differences in the association between prediabetes and cardiovascular diseases in China: A national cross-sectional study","authors":"Shuo Xie, Liping Yu, Fei Chen, Yao Wang, Ruifen Deng, Xue-Lian Zhang, Bo Zhang","doi":"10.4239/wjd.v15.i2.240","DOIUrl":"https://doi.org/10.4239/wjd.v15.i2.240","url":null,"abstract":"BACKGROUND\u0000 Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, the global burden of which is rising. It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults. To develop a focused screening plan and treatment for Chinese adults with prediabetes, it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.\u0000 AIM\u0000 To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.\u0000 METHODS\u0000 The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008. A thorough evaluation was conducted. Individuals with prediabetes were categorized into two groups based on age. Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years. Random forest was established in both age groups. SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.\u0000 RESULTS\u0000 In total, 6948 people were diagnosed with prediabetes in this study. In pre-diabetes, prevalences of CVD were 5 (0.29%) in the younger group and 148 (2.85%) in the older group. Overall, 11.11% of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years. In the younger age group, the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle, whereas in the older age group, resident status was more closely linked.\u0000 CONCLUSION\u0000 The susceptibility to CVD is age-specific in newly diagnosed prediabetes. It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.","PeriodicalId":509005,"journal":{"name":"World Journal of Diabetes","volume":"34 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139776053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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