{"title":"Zebrafish as a preclinical model for diabetes mellitus and its complications: From monogenic to gestational diabetes and beyond.","authors":"Jie Huang, Yin-Ling Chen","doi":"10.4239/wjd.v16.i5.100574","DOIUrl":"10.4239/wjd.v16.i5.100574","url":null,"abstract":"<p><p>With diabetes currently affecting 537 million people globally, innovative research approaches are urgently required. Zebrafish (<i>Danio rerio</i>) has emerged as a pivotal model organism in diabetes research, particularly valuable for developmental biology studies and preclinical therapeutic validation. Its rapid life cycle, optical transparency, and genetic tractability collectively enable efficient longitudinal observation of pathological progression and pharmacological responses. Utilizing zebrafish models, researchers have elucidated fundamental mechanisms governing islet development, β-cell dysfunction, and metabolic dysregulation. These experimental systems have significantly advanced our understanding of various diabetes subtypes, including type 1, type 2, gestational, and monogenic forms, while also facilitating mechanistic studies of diabetic complications such as retinopathy and nephropathy. Recent model refinements, particularly in simulating monogenic disorders and pregnancy-associated metabolic changes, promise to deepen our comprehension of disease pathophysiology and therapeutic interventions. Nevertheless, a persistent limitation lies in their incomplete recapitulation of human-specific physiological complexity and multi-organ metabolic interactions, factors that may influence translational applicability. Despite these constraints, zebrafish-based research continues to provide an indispensable platform for diabetes investigation, holding significant promise for alleviating the escalating global burden of this metabolic disorder.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"100574"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased colorectal cancer risk in prediabetes: A meta-analysis.","authors":"Na Wang, Tian-Yi Zhao, Xiao Ma","doi":"10.4239/wjd.v16.i5.103403","DOIUrl":"10.4239/wjd.v16.i5.103403","url":null,"abstract":"<p><strong>Background: </strong>Previous research yielded conflicting results regarding the association between prediabetes and colorectal cancer (CRC).</p><p><strong>Aim: </strong>To systematically assess the incidence of CRC in individuals with prediabetes compared with individuals with normoglycemia <i>via</i> a meta-analysis.</p><p><strong>Methods: </strong>Relevant cohort studies were acquired by searching MEDLINE, Web of Science, and EMBASE. A random-effects model was applied to combine the findings after accounting for heterogeneity. Several subgroup analyses were conducted to assess the impact of study characteristics on the results.</p><p><strong>Results: </strong>Eleven cohort studies involving 4996352 participants, including 383917 (7.7%) with prediabetes at baseline, were analyzed in this meta-analysis. Over a mean follow-up period of 6.5 years, the combined findings revealed that individuals with prediabetes at baseline had a higher likelihood of developing CRC than those with normoglycemia [risk ratio (RR) = 1.18, 95% confidence interval = 1.11 to 1.25, <i>P</i> < 0.001] with low statistical heterogeneity (<i>I</i> <sup>2</sup> = 27%). Subgroup analyses indicated that the association between prediabetes and an increased risk of CRC was mainly observed in studies defining prediabetes using impaired fasting glucose (RR = 1.24) and slightly elevated hemoglobin A1c levels (RR = 1.18) but not in those that defined prediabetes using impaired glucose tolerance (RR = 1.06). Other study characteristics such as design, country, participant age and sex, the duration of follow-up, or adjustment for body mass index did not significantly impact the results (all <i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>People with prediabetes might have a higher likelihood of developing CRC than individuals with normoglycemia.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"103403"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aucubin mitigates the elevation of microglial aerobic glycolysis and inflammation in diabetic neuropathic pain <i>via</i> aldose reductase.","authors":"Xue-Zhen Zheng, Hong-Yan Yu, Ye-Ru Chen, Jian-Sheng Fang","doi":"10.4239/wjd.v16.i5.103915","DOIUrl":"10.4239/wjd.v16.i5.103915","url":null,"abstract":"<p><strong>Background: </strong>Treatment of diabetic neuropathy is often limited by side effects. Aucubin, an iridoid glycoside derived from natural plants, exhibits notable anti-inflammatory and antioxidant properties.</p><p><strong>Aim: </strong>To investigate the effects of aucubin on diabetic neuropathic pain (DNP) and glycolysis and inflammation in microglia.</p><p><strong>Methods: </strong>Streptozotocin (STZ) was used to establish a DNP animal model. Blood glucose levels and body weight of mice were measured following STZ administration. Paw withdrawal threshold was calculated for mechanical allodynia. Paw withdrawal latency was recorded for thermal hyperalgesia. The open field test and elevated plus maze was used to assess locomotor activity and anxiety-like behavior. Western blotting was utilized for analysis of protein expression. Immunofluorescence staining was measured for morphometric analysis of microglia. Glycolysis and ATP synthesis in BV-2 cell lines were detected by metabolic extracellular flux analysis. The SwissTargetPrediction and STRING databases were used for comprehensive screening to identify potential target proteins for aucubin. The molecular docking between the possible target proteins and aucubin was investigated using Auto Dock Tool. The BV-2 cell line was transfected with lentiviral AKR1B1-shRNA to further ascertain the function of AKR1B1 in the impact of aucubin on aerobic glycolysis and inflammation during high glucose stimulation.</p><p><strong>Results: </strong>Aucubin significantly improved pain and anxiety-like behavior in STZ-induced diabetic mice and restored microglial aerobic glycolysis and inflammation. Several public databases and molecular docking studies suggested that AKR1B1, MMP2 and MMP9 are involved in the effect of aucubin on DNP. Aucubin failed to restore aerobic glycolysis and inflammation in the context of AKR1B1 deficiency.</p><p><strong>Conclusion: </strong>Aucubin has potential as a therapeutic agent for alleviating DNP by inhibiting expression of AKR1B1.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"103915"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparisons of various insulin resistance indices for new-onset metabolic syndrome before midlife: The CHIEF cohort study, 2014-2020.","authors":"Wei-Nung Liu, Yi-Chiung Hsu, Yen-Po Lin, Kun-Zhe Tsai, Yen-Chen Lin, Pang-Yen Liu, Gen-Min Lin","doi":"10.4239/wjd.v16.i5.101840","DOIUrl":"10.4239/wjd.v16.i5.101840","url":null,"abstract":"<p><strong>Background: </strong>Some non-insulin-based insulin resistance (IR) indices have been found to be associated with metabolic syndrome (MetS); however, few cohort studies have compared the capacities of these indices for predicting incident MetS in young adults.</p><p><strong>Aim: </strong>To investigate the associations of various non-insulin-based IR (NI-IR) indices with new-onset MetS in young military personnel.</p><p><strong>Methods: </strong>A total of 2890 armed forces personnel in Taiwan who were aged 18-39 years and did not have MetS at baseline were followed to monitor the incidence of new-onset MetS from 2014 to the end of 2020. Six NI-IR indices, including the metabolic score for IR (METS-IR), triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio, TG glucose (TyG) index, Zhejiang University (ZJU) index, total cholesterol (TC)-to-HDL-C ratio, and alanine transaminase (ALT)-to-aspartate transaminase (AST) ratio, were defined according to specific criteria<i>.</i> Incident MetS was identified on the basis of each annual health examination using the International Diabetes Federation criteria. Multiple Cox regression analyses were conducted, adjusting for age, sex, waist circumference, smoking status, alcohol consumption status, and physical activity, to assess the associations of the NI-IR indices with incident MetS. The area under the receiver operating characteristic curve (AUROC) was used to compare the capacities of these NI-IR indices for predicting new-onset MetS.</p><p><strong>Results: </strong>During a median follow-up of 5.8 years, there were 673 patients with new-onset MetS (23%). All six of the NI-IR indices were significantly and positively associated with incident MetS. In the entire cohort, the greatest AUROC was found for the METS-IR [0.782; 95% confidence interval (CI): 0.762-0.801; all <i>P</i> values compared to the other NI-IR indices < 0.05], followed by the TG/HDL-C ratio (0.752; 95%CI: 0.731-0.772), ZJU index (0.743; 95%CI: 0.722-0.764), TyG index (0.734; 95%CI: 0.713-0.756), TC/HDL-C ratio (0.731; 95%CI: 0.709-0.752), and then the ALT/AST ratio (0.734; 95%CI: 0.713-0.756).</p><p><strong>Conclusion: </strong>This study suggests that almost all the NI-IR indices are associated with the development of MetS in military young adults. The METS-IR is the strongest predictor of new-onset MetS before midlife.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"101840"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of ranibizumab on diabetic retinopathy <i>via</i> the vascular endothelial growth factor/STAT3/glial fibrillary acidic protein pathway.","authors":"Ye-Ting Lin, Jian Tan, Yu-Lin Tao, Wei-Wen Hu, Yi-Cang Wang, Jing Huang, Qiong Zhou, Ang Xiao","doi":"10.4239/wjd.v16.i5.99473","DOIUrl":"10.4239/wjd.v16.i5.99473","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is the leading cause of vision loss in patients with diabetes. The vascular endothelial growth factor (VEGF) pathway plays a critical role in the pathogenesis of DR, and ranibizumab, an anti-VEGF agent, has shown promise in its treatment. Signal transducer and activator of transcription 3 (STAT3) is involved in inflammatory processes and cellular signaling, while glial fibrillary acidic protein (GFAP) is a marker of glial cell activation, both contributing to retinal damage in DR. However, the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.</p><p><strong>Aim: </strong>To investigate the role of ranibizumab in early DR <i>via</i> the VEGF/STAT3/GFAP pathway.</p><p><strong>Methods: </strong>Adult retinal pigment epithelial 19 (ARPE-19) cells and human retinal microvascular endothelial cells (HRMECs) were cultured under high-glucose conditions to simulate a diabetic environment. The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis. A diabetic rat model was induced with streptozotocin (60 mg/kg). Retinal changes, including retinal ganglion cell (RGC) apoptosis, vascular alterations, and cytokine expression, were evaluated using fundus fluorescein angiography, hematoxylin and eosin and periodic acid Schiff staining, immunofluorescence, confocal imaging, and Western blot analysis.</p><p><strong>Results: </strong>High-glucose conditions significantly increased the mRNA and protein levels of VEGF, STAT3, GFAP, and other cytokines in ARPE-19 and HRMECs. However, these levels were partially suppressed by ranibizumab. RGC apoptosis, vascular leakage, and elevated cytokine expression were observed during early-stage DR in diabetic rats. Ranibizumab treatment in diabetic rats reduced cytokine expression, restored RGCs, and repaired vascular networks.</p><p><strong>Conclusion: </strong>Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway, suppresses cytokine expression, and promotes retinal repair, effectively delaying or preventing early DR progression.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"99473"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of nuclear factor erythroid 2-related factor 2 in negative pressure wound therapy for diabetic foot ulcers.","authors":"Hao-Jie Sun, Shan-Wen Si, Ya-Mei Ma, Xue-Kui Liu, Hou-Fa Geng, Jun Liang","doi":"10.4239/wjd.v16.i5.104350","DOIUrl":"10.4239/wjd.v16.i5.104350","url":null,"abstract":"<p><strong>Background: </strong>Negative pressure wound therapy (NPWT) is a potential treatment for diabetic foot ulcers (DFUs), although the mechanisms underlying its effectiveness remain unclear. This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like epichlorohydrin-associated protein 1 (Keap1) signaling pathway, which is crucial for the body's defense against oxidative stress. The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process. There are still limited data on the roles of Nrf2, its downstream signaling molecules, and angiogenesis markers in patients undergoing NPWT.</p><p><strong>Aim: </strong>To study the mechanism of NPWT in DFUs.</p><p><strong>Methods: </strong>This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital, who were divided into Control group (<i>n</i> = 21) and NPWT group (<i>n</i> = 19). The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment. The wound condition, erythrocyte sedimentation rate (ESR), procalcitonin (PCT), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), cluster of differentiation 31 (CD31), and levels of oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC)] were analyzed before and 7 days after treatment by the Mann-Whitney <i>U</i> test.</p><p><strong>Results: </strong>The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment. The levels of ESR, PCT, IL-6, and TNF-α were significantly reduced in the NPWT group compared to the control group (<i>P</i> < 0.05), while the levels of CD31, VEGF, and b-FGF showed significant increases (<i>P</i> < 0.05). The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets (SOD, CAT, and T-AOC), accompanied by decreases in the levels of Keap1 and MDA (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress. Its effects could possibly be enhanced through the action of Nrf2.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"104350"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chang Seong Kim, Sang Heon Suh, Hong Sang Choi, Eun Hui Bae, Seong Kwon Ma, Bongseong Kim, Kyung-Do Han, Soo Wan Kim
{"title":"Impact of diabetes duration and hyperglycemia on the progression of diabetic kidney disease: Insights from the KNHANES 2019-2021.","authors":"Chang Seong Kim, Sang Heon Suh, Hong Sang Choi, Eun Hui Bae, Seong Kwon Ma, Bongseong Kim, Kyung-Do Han, Soo Wan Kim","doi":"10.4239/wjd.v16.i5.102094","DOIUrl":"10.4239/wjd.v16.i5.102094","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is a significant risk factor for chronic kidney disease, and diabetic kidney disease (DKD) is prevalent among patients with diabetes. Previous studies have indicated that the duration of diabetes and poor glycemic control are associated with an increased risk of DKD, but data on how the duration and severity of hyperglycemia specifically relate to DKD progression are limited.</p><p><strong>Aim: </strong>To investigate the relationship between diabetes duration and glycemic control, and DKD progression in South Korea.</p><p><strong>Methods: </strong>We included 2303 patients with diabetes using the 2019-2021 Korea National Health and Nutrition Examination Surveys data. DKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m<sup>2</sup>, urinary albumin-to-creatinine ratio ≥ 30 mg/g, or both. Diabetes duration and severity were classified into six categories each.</p><p><strong>Results: </strong>DKD prevalence was 25.5%. The DKD risk significantly increased in diabetes lasting 10-15 years or hemoglobin A1C (HbA1c) ≥ 8% compared to patients with newly diagnosed diabetes or HbA1c < 6.5%. Albuminuria developed with shorter diabetes duration and lower HbA1c than eGFR decline. The adjusted odds ratios for DKD were 3.77 [95% confidence interval (95%CI): 2.60-5.45] and 4.91 (95%CI: 2.80-8.63) in patients with diabetes lasting ≥ 20 years and HbA1c ≥ 10%, respectively, compared to those with new-onset diabetes and HgA1c < 6.5%.</p><p><strong>Conclusion: </strong>Patients with diabetes lasting > 10 years or HbA1c > 8% had a higher risk of DKD, emphasizing the importance of early monitoring and management is crucial to prevent DKD progression.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"102094"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intelligent hydrogel-based dressings for treatment of chronic diabetic wounds.","authors":"Huan Liu, Li He","doi":"10.4239/wjd.v16.i5.104937","DOIUrl":"10.4239/wjd.v16.i5.104937","url":null,"abstract":"<p><p>Diabetic wounds represent a significant challenge in the medical field, significantly impacting patient quality of life and imposing a heavy burden on healthcare systems. Intelligent hydrogel dressings have attracted significant attention in diabetic wound treatment due to their unique properties. This review systematically explores the three main categories of intelligent hydrogels (natural, synthetic, and composite), dissecting their composition, structure, and the mechanisms that enable their intelligent responses. The crucial roles of these dressings in maintaining a moist wound environment, efficiently absorbing exudate, and precisely delivering drugs are expounded. Moreover, their application advantages in combating bacteria and infections, regulating inflammation and immunity, promoting angiogenesis and tissue regeneration, as well as enabling real-time monitoring and personalized treatment, are explored in depth. Additionally, we discuss future research directions and the prospects for personalized precision medicine in diabetic wound care, aiming to inspire innovation and provide a comprehensive theoretical basis for the development of next-generation intelligent dressings.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"104937"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anemia risk and mitigation strategies in type 2 diabetic patients: The role of novel antidiabetic agents.","authors":"Petra Meliš, Maja Cigrovski Berkovic","doi":"10.4239/wjd.v16.i5.105549","DOIUrl":"10.4239/wjd.v16.i5.105549","url":null,"abstract":"<p><p>Anemia is a common yet often overlooked complication in patients with type 2 diabetes mellitus (T2DM), particularly those with chronic kidney disease. It significantly impacts patients' quality of life, cardiovascular health, and treatment outcomes. Despite its high prevalence, current clinical guidelines lack specific recommendations for anemia prevention and management in T2DM, especially in the context of newer antidiabetic therapies. This review explores the potential of emerging antidiabetic medications, such as sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and combined GLP-1-RA/GIP to mitigate anemia risk. Early detection and management of anemia in T2DM patients are crucial for improving glycemic control, reducing cardiovascular morbidity, and enhancing overall treatment outcomes. This review underscores the need for further research to better understand the mechanisms by which these novel therapies influence anemia risk and to integrate these findings into clinical practice.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"105549"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian-Yun Mao, Hui Ran, Qiu-Yue Hu, Sun-Yue He, Yao Lu, Han Li, Yi-Meng Chai, Zhao-Yin Chu, Xu Qian, Wan Ding, Yi-Xin Niu, Hong-Mei Zhang, Xiao-Yong Li, Qing Su
{"title":"Impaired efferocytosis by monocytes and monocyte-derived macrophages in patients with poorly controlled type 2 diabetes.","authors":"Qian-Yun Mao, Hui Ran, Qiu-Yue Hu, Sun-Yue He, Yao Lu, Han Li, Yi-Meng Chai, Zhao-Yin Chu, Xu Qian, Wan Ding, Yi-Xin Niu, Hong-Mei Zhang, Xiao-Yong Li, Qing Su","doi":"10.4239/wjd.v16.i5.101473","DOIUrl":"10.4239/wjd.v16.i5.101473","url":null,"abstract":"<p><strong>Background: </strong>Deficient efferocytosis (<i>i.e.</i>, phagocytic clearance of apoptotic cells) by macrophages has been frequently reported in experimental models of type 2 diabetes (T2D).</p><p><strong>Aim: </strong>To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.</p><p><strong>Methods: </strong>Overall, 30 patients with poorly controlled T2D [glycosylated hemoglobin (HbA1c) ≥ 8.0%] and 30 age- and sex-matched control subjects were enrolled in the study. The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining. Macrophage membrane CD14 expression was examined by flow cytometry. Metabolic factors such as 25(OH)D and immune factors such as interleukin-1β were also measured.</p><p><strong>Results: </strong>The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group. Notably, efferocytosis remained impaired after monocytes differentiated into macrophages. Additionally, the percentages of classical monocytes (CD14<sup>++</sup>CD16<sup>-</sup> monocytes) and CD14<sup>+</sup> macrophages were significantly lower in the diabetes group. Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level, and that the macrophage efferocytosis index was significantly associated with the percentage of CD14<sup>+</sup> macrophages.</p><p><strong>Conclusion: </strong>Impaired efferocytosis was observed in T2D patients, with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages. The efferocytosis index was negatively associated with metrics of glycemic control, and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 5","pages":"101473"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}