Group-informed attentive framework for enhanced diabetes mellitus progression prediction.

The increasing prevalence of Diabetes Mellitus (DM) as a global health concern highlights the paramount importance of accurately predicting its progression. This necessity has propelled the use of deep learning's advanced analytical and predictive capabilities to the forefront of current research. However, this approach is confronted with significant challenges, notably the prevalence of incomplete data and the need for more robust predictive models. Our research aims to address these critical issues, leveraging deep learning to enhance the precision and reliability of diabetes progression predictions. We address the issue of missing data by first locating individuals with data gaps within specific patient clusters, and then applying targeted imputation strategies for effective data imputation. To enhance the robustness of our model, we implement strategies such as data augmentation and the development of advanced group-level feature analysis. A cornerstone of our approach is the implementation of a deep attentive transformer that is sensitive to group characteristics. This framework excels in processing a wide array of data, including clinical and physical examination information, to accurately predict the progression of DM. Beyond its predictive capabilities, our model is engineered to perform advanced feature selection and reasoning. This is crucial for understanding the impact of both individual and group-level factors on deep models' predictions, providing invaluable insights into the dynamics of DM progression. Our approach not only marks a significant advancement in the prediction of diabetes progression but also contributes to a deeper understanding of the multifaceted factors influencing this chronic disease, thereby aiding in more effective diabetes management and research.

Bridging metabolic syndrome and cognitive dysfunction: role of astrocytes.

Metabolic syndrome (MetS) and cognitive dysfunction pose significant challenges to global health and the economy. Systemic inflammation, endocrine disruption, and autoregulatory impairment drive neurodegeneration and microcirculatory damage in MetS. Due to their unique anatomy and function, astrocytes sense and integrate multiple metabolic signals, including peripheral endocrine hormones and nutrients. Astrocytes and synapses engage in a complex dialogue of energetic and immunological interactions. Astrocytes act as a bridge between MetS and cognitive dysfunction, undergoing diverse activation in response to metabolic dysfunction. This article summarizes the alterations in astrocyte phenotypic characteristics across multiple pathological factors in MetS. It also discusses the clinical value of astrocytes as a critical pathologic diagnostic marker and potential therapeutic target for MetS-associated cognitive dysfunction.

Evolution and global research trends of immunity in diabetic nephropathy: a bibliometric and visual analysis from 2004 to 2023.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, with an increasing prevalence worldwide, but its pathomechanisms remain incompletely understood. Accumulating evidence suggests that immunity plays an important role in the development of DN. Many papers have been published in the field over the last 20 years, but there has been no bibliometric review of the research hotspots and trends in the field. This study aimed to assess the current research status and future trends of the link between immune and DN using bibliometric analysis. METHODS: Publications on the association between immunity and DN from 2004 to 2023 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were employed to visualize research trends and hotspots in the field. Data including author, institution, country, journal, reference, and keyword were analyzed. RESULTS: Ultimately 1246 publications meeting the criteria were included in the bibliometric analysis, involving 838 articles (84.96%) and 408 reviews (15.04%). The literature covered 81 countries and regions, 1751 institutions, and 6584 authors. The top 2 countries in terms of the number of publications were China (435) and the United States (318), and they collaborated most frequently. The United States had the highest number of citations for published papers (18,161), far exceeding the other countries. England had 38 publications but had the highest average number of citations (92.32). The University of California system was the most prolific institution (25 papers, 1062 citations, 42.48 citations per paper). Frontiers in Immunology was the most prolific journal in the field (30 papers). The most cited journal was Kidney International (863 citations). The analysis of keywords and references showed that inflammation, ferroptosis, and lipid metabolism may be future research hotspots in this field. CONCLUSIONS: The number of publications related to immunity and DN has increased annually over the past 20 years, with a significant increase in the last 3 years especially. Our results identified research hotspots and trends in the field. These findings provide valuable perspectives for future research, enhancing our understanding of the immune-related mechanisms of DN and exploring potential therapeutic strategies.

Aging adipose tissue, insulin resistance, and type 2 diabetes.

With the increase of population aging, the prevalence of type 2 diabetes (T2D) is also rising. Aging affects the tissues and organs of the whole body, which is the result of various physiological and pathological processes. Adipose tissue has a high degree of plasticity and changes with aging. Aging changes the distribution of adipose tissue, affects adipogenesis, browning characteristics, inflammatory status and adipokine secretion, and increases lipotoxicity. These age-dependent changes in adipose tissue are an important cause of insulin resistance and T2D. Understanding adipose tissue changes can help promote healthy aging process. This review summarizes changes in adipose tissue ascribable to aging, with a focus on the role of aging adipose tissue in insulin resistance and T2D.

Evidential support for garlic supplements against diabetic kidney disease: a preclinical meta-analysis and systematic review.

Garlic (Allium sativum L.) is a popular spice that is widely used for food and medicinal purposes and has shown potential effects on diabetic kidney disease (DKD). Nevertheless, systematic preclinical studies are still lacking. In this meta-analysis and systematic review, we evaluated the role and potential mechanisms of action of garlic and its derived components in animal models of DKD. We searched eight databases for relevant studies from the establishment of the databases to December 2022 and updated in April 2023 before the completion of this review. A total of 24 trials were included in the meta-analysis. It provided preliminary evidence that supplementing with garlic could improve the indicators of renal function (BUN, Scr, 24 h urine volume, proteinuria, and KI) and metabolic disorders (BG, insulin, and body weight). Meanwhile, the beneficial effects of garlic and its components in DKD could be related to alleviating oxidative stress, suppressing inflammatory reactions, delaying renal fibrosis, and improving glucose metabolism. Furthermore, time-dose interval analysis exhibited relatively greater effectiveness when garlic products were supplied at doses of 500 mg kg-1 with interventions lasting 8-10 weeks, and garlic components were administered at doses of 45-150 mg kg-1 with interventions lasting 4-10 weeks. This meta-analysis and systematic review highlights for the first time the therapeutic potential of garlic supplementation in animal models of DKD and offers a more thorough evaluation of its effects and mechanisms to establish an evidence-based basis for designing future clinical trials.

Preferences and Adherence of People with Prediabetes for Disease Management and Treatment: A Systematic Review.

Objective: To comprehensively summarize the evaluation, preference, and expectations of people with prediabetes regarding the management and treatment of pre-diabetes. Methods: Search PubMed, Embase, Web of Science, Cochrane Library and CNKI for articles about prediabetes, preferences, and expectations from inception of the database to June 2023. Results: A total of 18 studies involving 17,240 participants with prediabetes were included. Although the preferences and views of people with prediabetes vary widely, there are certain trends: 1) Compared with drug therapy, people with prediabetes prefer exercise and nutrition therapies. 2) People with prediabetes expect intensive lifestyle interventions guided by professionals. 3) Effective communication between doctors and people with prediabetes is crucial for promoting the development and implementation of treatment plans. Conclusion: The results of this systematic review showed that people with prediabetes prefer intensive lifestyle interventions due to concerns about drug side effects, dependency, and other factors. In addition, drug acceptance and lifestyle interventions options differed among different populations, which emphasized the significance of individualized therapy.

Corrigendum: Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fendo.2023.1169405.].

Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis.

Although there was no significant heterogeneity in the meta-publication, sensitivity analyses revealed significant heterogeneity. Overall, the prevalence was higher in women (N = 6, R = 4.6%, 95% CI 3.1%, 6.0%, and I2 = 99.8%) than in men (N = 6, R = 3.4%, 95% CI 2.0%, 4.7%, and I2 = 99.6the %); prevalence of type 2 diabetes (N = 9, R = 12.5%, 95% CI 7.7%, 17.3%, and I2 = 95.4%) was higher than type 1 diabetes (N = 7, R = 8.3%, 95% CI 6.4%, 10.2%, and I2 = 93.6%); the prevalence of DGP was slightly lower in DM patients aged over 60 years (N = 6, R = 5.5%, 95% CI 3.3%, 7.7%, and I2 = 99.9%) compared to patients under 60 years of age (N = 12, R = 15.8%, 95% CI 11 15.8%, 95% CI 11.4%, 20.2%, and I2 = 88.3%). In conclusion, our findings indicate that the combined estimated prevalence of gastroparesis in diabetic patients is 9.3%. However, the sensitivity of the results is high, the robustness is low, and there are significant bias factors. The subgroup analysis revealed that the prevalence of DM-DGP is associated with factors such as gender, diabetes staging, age, and study method.

The relationship between vitamin D deficiency and diabetic foot ulcer: A meta-analysis.

A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, -7.14; 95% CI, -8.83 to -5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63-3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis.

Objective: Vascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A (so called VEGF) may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN. Methods: This study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect. Results: 14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12[1.34, 2.90], p<0.00001) and healthy people (SMD:3.50[2.24, 4.75], p<0.00001). In addition, increased circulating VEGF levels were not associated with an increased risk of DPN (OR:1.02[0.99, 1.05], p<0.00001). Conclusion: Compared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN.

Potential effects of bisphenol A on diabetes mellitus and its chronic complications: A narrative review.

Diabetes mellitus (DM) is a metabolic disease caused by multiple factors such as genetics, environment, and lifestyle. Bisphenol A (BPA), as one of the most common endocrine-disrupting chemicals (EDCs), has been strongly implicated in the development of type 2 diabetes mellitus (T2DM). BPA exposure is associated with target organ damage in DM and may exacerbate the progression of some chronic complications of DM. This paper reviews relevant epidemiological, in vivo, and in vitro studies to better understand BPA's potential risk associations and pathological mechanisms in several chronic diabetic complications.

Efficacy of traditional Chinese medicine injection for diabetic kidney disease: A network meta analysis and systematic review.

Background: Diabetic kidney disease (DKD) is an important public health problem worldwide that increases the mortality of patients and incurs high medical costs. Traditional Chinese Medicine injections (TCMIs) are widely used in clinical practice. However, their efficacy is unknown owing to a lack of definitive evidence. This study conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of traditional Chinese medicine injections in the treatment of DKD to provide a reference for clinical treatment. Methods: Total 7 databases had been searched, which included PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese scientific journal database (VIP), WanFang, and SinoMed. Only randomised controlled trials (RCT) had been included for analysis. The retrieval time limit was from the establishment of the database until 20 July 2022. Cochrane Risk of Bias 2.0 tool was used to evaluate the quality of the studies. Network meta-analyses, and Trial Sequential Analyses (TSA) were used to analysis the effectiveness of the included RCTs for DKD. The Stata 15.1 and R 4.0.4 were used to perform the network meta-analysis. Sensitivity analysis was used to assess the robustness of the findings. The effect of the intervention evidence are summarized on the basis of the minimum background framework. Results: NMA showed that the total effective rate of SMI, DCI, DHI, HQI, and SKI combined with alprostadil injection (PGE1) was better than PGE1 single used. Based on the surface under the cumulative ranking curve values, PGE1+DHI was the most effective for urinary albumin excretion rate and 24 h urinary albumin, PGE1+HQI was the most effective for the total response rate and ß2-MG, and PGE1+SKI was the most effective for serum creatinine and blood urea nitrogen. Cluster analysis found that PGE1+HQI and PGE1+SKI could be the best treatments in terms of primary outcome measures. PGE1+SKI was found to be most effective on glomerular filtration function. PGE1+DHI was most effective for urinary protein-related indices. Conclusion: The efficacy of TCMI combined with PGE1 was higher than PGE1 single used. PGE1+HQI and PGE1+SKI were the most effective treatments. The safety of TCMI treatment should be investigated further. This study needs to be validated using large-sample, double-blind, multicentre RCTs. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=348333], identifier [CRD42022348333].

Potential causal association between leisure sedentary behaviors, physical activity and musculoskeletal health: A Mendelian randomization study.

BACKGROUND: Increasing evidence shows that leisure sedentary behaviors (LSB) and physical activity (PA) are associated with various musculoskeletal disorders. However, the causality between LSB/PA and musculoskeletal health remained unknown. In this study, we aimed to evaluate the causal relationships between LSB/PA and lower back pain (LBP), intervertebral disc disorder (IVDD), rheumatoid arthritis (RA), and bone mineral density (BMD) by using a two-sample Mendelian randomization method. METHODS: The exposure data were obtained from large-scale genome-wide association studies (GWAS), including the PA dataset (self-reported PA, n = 377,234; accelerometer-assessed PA, n = 91,084) and LSB dataset (n = 422,218). The outcome data were derived from the FinnGen LBP dataset (n = 248,528), FinnGen IVDD dataset (n = 256,896), BMD GWAS dataset (n = 56,284), and RA GWAS dataset (n = 58,284). The causal relationships were estimated with inverse variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analyses were performed with Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to estimate the robustness of our findings. RESULTS: Genetically predicted leisure television watching increased the risk of LBP (OR = 1.68, 95% CI 1.41 to 2.01; P = 8.23×10-9) and IVDD (OR = 1.62, 95% CI 1.37 to 1.91; P = 2.13 × 10-8). In addition, this study revealed a potential causal relationship between computer use and a reduced risk of IVDD (OR = 0.60, 95% CI 0.42 to 0.86; P = 0.005) and RA (OR = 0.28, 95% CI 0.13 to 0.60; P = 0.001). CONCLUSIONS: Our results suggest that leisure television watching is a risk factor for LBP and IVDD, whereas leisure computer use may act as a protective factor against IVDD and RA. These findings emphasized the importance of distinguishing between different sedentary behaviors in musculoskeletal disease studies.

Sleep traits, fat accumulation, and glycemic traits in relation to gastroesophageal reflux disease: A Mendelian randomization study.

Background: Sleep traits, fat accumulation, and glycemic traits are associated with gastroesophageal reflux disease (GERD) in observational studies. However, whether their associations are causal remains unknown. We performed a Mendelian randomization (MR) study to determine these causal relationships. Methods: Independent genetic variants associated with insomnia, sleep duration, short sleep duration, body fat percentage, visceral adipose tissue (VAT) mass, type 2 diabetes, fasting glucose, and fasting insulin at the genome-wide significance level were selected as instrumental variables. Summary-level data for GERD were derived from a genome-wide association meta-analysis including 78,707 cases and 288,734 controls of European descent. Inverse variance weighted (IVW) was used for the main analysis, with weighted median and MR-Egger as complements to IVW. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to estimate the stability of the results. Results: The MR study showed the causal relationships of genetically predicted insomnia (odds ratio [OR] = 1.306, 95% confidence interval [CI] 1.261 to 1.352; p = 2.24 × 10-51), short sleep duration (OR = 1.304, 95% CI: 1.147 to 1.483, p = 4.83 × 10-5), body fat percentage (OR = 1.793, 95% CI 1.496 to 2.149; p = 2.68 × 10-10), and visceral adipose tissue (OR = 2.090, 95% CI 1.963 to 2.225; p = 4.42 × 10-117) with the risk of GERD. There was little evidence for causal associations between genetically predicted glycemic traits and GERD. In multivariable analyses, genetically predicted VAT accumulation, insomnia, and decreased sleep duration were associated with an increased risk of GERD. Conclusion: This study suggests the possible roles of insomnia, short sleep, body fat percentage, and visceral adiposity in the development of GERD.

[Role of NLRP3 inflammasome in diabetic neuropathy and prevention and treatment with traditional Chinese medicine].

As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid ß(Aß)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.

Effects of Sheng-Mai Injection on Diabetes Mellitus: A Systematic Review and Meta-analysis.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder characterized by progressive ß cell dysfunction. Sheng-Mai Injection (SMI), a Traditional Chinese medicine preparation, is widely used for DM and its related complications. OBJECTIVE: This meta-analysis aimed to summarize the applications of SMI in DM and related complications. METHODS: Eight databases were searched, and meta-analyses were performed. RESULTS: Fifteen studies, including 1273 participants, were included. All studies and participants included were from China. Pooled effects showed that SMI might reduce glycated hemoglobin (MD -0.46%; 95% CI -0.89 to -0.03; P < 0.01), fasting blood glucose (MD -0.83 mmol/L; 95% CI -1.30 to -0.36; P < 0.01), two-hour postprandial glucose (MD -1.27 mmol/L; 95% CI -1.96 to -0.58; P < 0.01), 24-hour urinary protein (MD -0.28 mg; 95% CI -0.51 to -0.06; P = 0.01), blood urea nitrogen (MD -1.31 mg; 95% CI -2.08 to -0.54; P < 0.05), Scr (MD -2.60; 95% CI -3.43 to -1.77; P < 0.05), ulnar nerve motor nerve conduction velocity (MNCV) (MD 1.45; 95% CI 0.03 to 2.87; P < 0.05), and tibial nerve sensory nerve conduction velocity (SNCV) (MD 1.84; 95% CI 0.1 to 3.58; P < 0.05). There was no evidence of an effect on common peroneal nervous MNCV and SNCV, tibial nerve MNCV, median nerve MNCV, and SNCV. Adverse effects included less frequent gastrointestinal reactions, elevated transaminase, leucopenia, fever, and rash. CONCLUSION: Combination use of SMI based on conventional hypoglycemic treatment can significantly improve HbA1c, FBG, and 2hPG in DM and reduce 24-hour urinary protein, Scr, and BUN in DM patients. SMI was found to have no effect on the neurological function of diabetic peripheral neuropathy.

The gut microbiota-astrocyte axis: Implications for type 2 diabetic cognitive dysfunction.

BACKGROUND: Diabetic cognitive dysfunction (DCD) is one of the most insidious complications of type 2 diabetes mellitus, which can seriously affect the ability to self-monitoring of blood glucose and the quality of life in the elderly. Previous pathological studies of cognitive dysfunction have focused on neuronal dysfunction, characterized by extracellular beta-amyloid deposition and intracellular tau hyperphosphorylation. In recent years, astrocytes have been recognized as a potential therapeutic target for cognitive dysfunction and important participants in the central control of metabolism. The disorder of gut microbiota and their metabolites have been linked to a series of metabolic diseases such as diabetes mellitus. The imbalance of intestinal flora has the effect of promoting the occurrence and deterioration of several diabetes-related complications. Gut microbes and their metabolites can drive astrocyte activation. AIMS: We reviewed the pathological progress of DCD related to the "gut microbiota-astrocyte" axis in terms of peripheral and central inflammation, intestinal and blood-brain barrier (BBB) dysfunction, systemic and brain energy metabolism disorders to deepen the pathological research progress of DCD and explore the potential therapeutic targets. CONCLUSION: "Gut microbiota-astrocyte" axis, unique bidirectional crosstalk in the brain-gut axis, mediates the intermediate pathological process of neurocognitive dysfunction secondary to metabolic disorders in diabetes mellitus.

Therapeutic effects of icariin and icariside II on diabetes mellitus and its complications.

Diabetes mellitus (DM) is a global health issue in the twenty-first century, and there are numerous challenges in preventing and alleviating its chronic complications. The herb Epimedium has beneficial therapeutic effects on various human diseases, including DM. Its major flavonoid component, icariin, has significant anti-DM activity and may help improve pancreatic ß-cell dysfunction and insulin resistance. Furthermore, preclinical evidence has shown that icariin and its in vivo bioactive form, icariside II, have preventive and therapeutic effects on several diabetic complications, including diabetic cardiomyopathy, diabetic vascular endothelial disorder, diabetic nephropathy, and diabetic erectile dysfunction. In this review, we present the general and toxicological information concerning icariin and icariside II and review the anti-DM effects of icariin from a molecular perspective. Additionally, we discuss the potential benefits of icariin and icariside II on the important pathological mechanisms of various diabetic complications. Despite positive preclinical evidence, additional investigations are needed before relevant clinical studies can be conducted. Therefore, we conclude with suggestions for future research. Hopefully, this review will provide a comprehensive molecular perspective for future research and product development related to icariin and icariside II in treating DM and diabetic complications.

Effects and Mechanisms of Ban-Xia Xie-Xin Decoction on Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Experimental Evidence.

BACKGROUND: Studies have indicated that Ban-Xia Xie-Xin Decoction (BXXXD) has therapeutic effects on type 2 diabetes mellitus (T2DM). However, due to the complexity of components and diversity of targets, the mechanisms are still not fully elucidated. OBJECTIVE: In this research, we systematically analysed the targets of BXXXD through the method of network pharmacology and further validated them through experiments. METHODS: The active components and therapeutic targets were identified, and these targets were analysed by the methods of gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analysis. Then, based on these network pharmacology analyses, we validated the main targets through animal experiments. RESULTS: A total of 169 active components and 159 targets were identified. KEGG analysis showed that the mitogen-activated protein kinase (MAPK) signalling pathway, tumour necrosis factor (TNF) signalling pathway, the phosphatidylinositol 3' -kinase (PI3K), Akt signalling pathway, and other pathways were related to the treatment of T2DM by BXXXD. PPI network analysis showed that the key genes included signal transducers and activators of transcription 3 (STAT3), JUN, TNF, Recombinant V-Rel Reticuloendotheliosis Viral Oncogene Homolog A (RELA), Akt/PKB- 1 (Protein kinase B), TP53, mitogen-activated protein kinase-1 (MAPK-1), mitogen-activated protein kinase-3 (MAPK-3), interleukin- 6 (IL6), and mitogen-activated protein kinase-14 (MAPK- 14), respectively. Animal experiments showed that BXXXD could reduce blood glucose and improve insulin resistance, which may be related to the mechanisms of inhibiting TNF, interleukin-1 (IL-1), IL-6, and interleukin-17 (IL-17) and promoting Akt phosphorylation. CONCLUSION: Our research revealed the mechanisms of BXXXD in the treatment of diabetes, which laid a solid foundation for further studies on the molecular mechanisms of BXXXD in the treatment of T2DM.