Diabetes Coronary Heart Disease Research Articles

Targeting oral-gut microbial transmission in diabetic coronary heart disease: unveiling key pathogenic mechanisms.

Targeting oral-gut microbial transmission in diabetic coronary heart disease: unveiling key pathogenic mechanisms.

Diabetes-Related Macrovascular Complications Are Associated With an Increased Risk of Diabetic Microvascular Complications: A Prospective Study of 1518 Patients With Type 1 Diabetes and 20 802 Patients With Type 2 Diabetes in the UK Biobank.

Diabetic vascular complications share common pathophysiological mechanisms, but the relationship between diabetes-related macrovascular complications (MacroVCs) and incident diabetic microvascular complications remains unclear. We aimed to investigate the impact of MacroVCs on the risk of microvascular complications. There were 1518 participants with type 1 diabetes (T1D) and 20 802 participants with type 2 diabetes from the UK Biobank included in this longitudinal cohort study. MacroVCs were defined by the presence of macrovascular diseases diagnosed after diabetes at recruitment, including coronary heart disease, peripheral artery disease, stroke, and ≥2 MacroVCs. The primary outcome was incident microvascular complications, a composite of diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy. During a median (interquartile range) follow-up of 11.61 (5.84-13.12) years and 12.2 (9.50-13.18) years, 596 (39.3%) and 4113 (19.8%) participants developed a primary outcome in T1D and type 2 diabetes, respectively. After full adjustment for conventional risk factors, Cox regression models showed significant associations between individual as well as cumulative MacroVCs and the primary outcome, except for coronary heart disease in T1D (T1D: diabetes coronary heart disease: 1.25 [0.98-1.60]; diabetes peripheral artery disease: 3.00 [1.86-4.84]; diabetes stroke: 1.71 [1.08-2.72]; ≥2: 2.57 [1.66-3.99]; type 2 diabetes: diabetes coronary heart disease: 1.59 [1.38-1.82]; diabetes peripheral artery disease: 1.60 [1.01-2.54]; diabetes stroke: 1.50 [1.13-1.99]; ≥2: 2.66 [1.92-3.68]). Subgroup analysis showed that strict glycemic (glycated hemoglobin <6.5%) and blood pressure (<140/90 mm Hg) control attenuated the association. Individual and cumulative MacroVCs confer significant risk of incident microvascular complications in patients with T1D and type 2 diabetes. Our results may facilitate cost-effective high-risk population identification and development of precise prevention strategies.

Oral-gut microbial transmission promotes diabetic coronary heart disease

BackgroundDiabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia–reperfusion injury (MIRI).MethodsWe comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice.ResultsSpecific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI.ConclusionOur findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.Graphic

NAD Pathways in Diabetic Coronary Heart Disease: Unveiling the Key Players.

Diabetic coronary heart disease is a global medical problem that poses a serious threat to human health, and its pathogenesis is complex and interconnected. Nicotinamide adenine dinucleotide (NAD) is an important small molecule used in the body that serves as a coenzyme in redox reactions and as a substrate for non-redox processes. NAD levels are highly controlled by various pathways, and increasing evidence has shown that NAD pathways, including NAD precursors and key enzymes involved in NAD synthesis and catabolism, exert both positive and negative effects on the pathogenesis of diabetic coronary heart disease. Thus, the mechanisms by which the NAD pathway acts in diabetic coronary heart disease require further investigation. This review first briefly introduces the current understanding of the intertwined pathological mechanisms of diabetic coronary heart disease, including insulin resistance, dyslipidemia, oxidative stress, chronic inflammation, and intestinal flora dysbiosis. Then, we mainly review the relationships between NAD pathways, such as nicotinic acid, tryptophan, the kynurenine pathway, nicotinamide phosphoribosyltransferase, and sirtuins, and the pathogenic mechanisms of diabetic coronary heart disease. Moreover, we discuss the potential of targeting NAD pathways in the prevention and treatment of diabetic coronary heart disease, which may provide important strategies to modulate its progression.

The mediation effect of HDL-C: Non-HDL-C on the association between inflammatory score and recurrent coronary events

BackgroundInflammation and lipids are both involved in the pathogenesis of coronary heart disease (CHD). However, the mediation effect of lipoproteins on the association between inflammation and recurrent coronary events in CHD patients remains unclear. MethodsThis was a retrospective study including CHD patients hospitalized in the Department of Cardiovascular Medicine in Sun Yat-sen Memorial Hospital between January 2011 and December 2012 with the endpoint of recurrent coronary events. The study calculated inflammatory score based on six serum inflammatory markers, including complement C3, complement C4, hyper-sensitive CRP, fibrinogen, D-dimer, and white blood cell count. Logistic regression analysis, subgroup analysis and mediation analysis were performed to assess the associations between inflammatory score and recurrent coronary events in different subpopulations and the identification of mediators. Inflammatory cytokine expression, cholesterol efflux capacity, and hepatic cholesterol influx were performed in additional CHD patients and healthy controls. ResultsThere were 191 CHD patients included in the analysis with a median inflammatory score of −0.78 (−2.17, 1.35) and 63 cases of recurrent coronary events. Subgroup logistic regression analysis demonstrated that inflammatory score was positively associated with recurrent coronary events only in the diabetic subgroup [OR: 1.241 (1.004, 1.534), P < 0.046]. HDL-cholesterol (HDL-C): non-HDL-C performed 46.74 % of negative mediation effect on this association. CHD patients had lower cholesterol efflux capacity than healthy controls, which was mediated by HDL: non-HDL ratio of 0.4. No difference was found in hepatic cholesterol influx between the two groups. ConclusionInflammatory score was associated with recurrent coronary events mediated by HDL-C: non-HDL-C ratio in diabetic CHD patients, indicating that lipoproteins might aggravate the inflammatory effect on atherosclerosis under hyperglycemia. Our findings suggested that anti-inflammatory and lipid-lowering therapies might be beneficial for this population.

PP37 A Systematic Review of Machine Learning and Statistical Models For Predicting Coronary Heart Disease In Diabetic Patients

IntroductionRisk prediction models, using either machine learning or statistical algorithms, can act as inputs of a cost-effectiveness model when predicting costs and effectiveness of an intervention. This systematic review has two objectives: to evaluate methodological quality of the published models to predict diabetic coronary heart disease (CHD) risk; to evaluate whether the models were sufficiently reported to judge their applicability to the cost-effectiveness modelling.MethodsA targeted review of journal articles published in English, Dutch, Chinese, or Spanish was undertaken in PubMed, Embase, Scopus, Web of Science, and IEEE Explore from 1 January, 2016 to 31 May, 2021. To assess the methodological quality and reporting of the models, we used PROBAST (Prediction model Risk Of Bias Assessment Tool), CHARMS (a Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies), and a checklist (Betts 2019) summarizing the application of cardiovascular risk prediction models to health technology assessment.ResultsOur search retrieved 6,579 hits, of which 18 models were eligible for inclusion. Among them, four studies developed machine learning models (2 recurrent neural networks, 1 random forest models, and 1 multi-task learning model) while 14 studies developed statistical models (8 Cox models, 5 logistic models, and 1 microsimulation model). More than 70 percent of models were of high methodological quality in aspects of participants (89%), predictors (72%), and outcomes (72%), while only five models (28%) in aspects of statistical analysis. For the reporting, only two models provided sufficient evidence in all aspects (i.e., participants, predictors, and outcomes) for judging their applicability to the cost-effectiveness modelling. Most models were reported sufficiently regarding participants (78%) and outcomes (72%), but only three models regarding predictors (17%).ConclusionsTo apply the CHD risk prediction models to cost-effectiveness modelling, concerns remain regarding the potential risk of bias due to inappropriate use of analysis methods, and regarding insufficient reporting on how to measure and assess the predictors.

Evidence and Potential Mechanisms of Traditional Chinese Medicine for the Adjuvant Treatment of Coronary Heart Disease in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.

The Implications of Smoking on Lipid Peroxidation and Serum Antioxidant Status in Young Smokers with Coronary Heart Disease

Cigarette smoking is one of the leading causes of heart disease. Cigarette smoke contains oxidants playing a major role in oxidative stress by lowering antioxidant capacity and by increasing the level of lipid peroxidation. The study aims to estimate the total antioxidant capacity levels, lipid peroxidation and its relation to cardiovascular disease in young smokers. The study contains three groups. Group1 includes 120 healthy controls as nonsmokers, group2 includes 120 young active smokers with coronary heart disease (CHD) and group3 includes 120 young active smokers with diabetic CHD subjects who were attending the SRM Medical College Hospital in Tamil Nadu for cardiology and medicine. The Total Antioxidant Capacity and lipid peroxidation especially measured as malondialdehyde (MDA) was determined using a spectrophotometric technique. Enzyme-linked Immune Sorbent Assay was used to measure oxidized LDL (ox- LDL)" and "high-sensitivity CRP (hs-CRP). The total antioxidant capacity of smokers was found to be significantly lower than those of healthy controls p&lt;0.0001. On the other hand, MDA, ox-LDL and hs-CRP concentrations were considerably higher in smokers than healthy controls p&lt;0.0001. Interestingly smoking burden and smoking intensity also show a significant correlation with antioxidant capacity, lipid peroxidation (MDA) as well as with ox-LDL. The study concludes that cigarette smoking reduces the concentration of total antioxidant required for free radical scavenging which enhances the rate of lipid peroxidation and is one of the risk factors for CHD observed in smokers.

Role of Cigarette Smoking on Serum Angiotensin-Converting Enzyme and Its Association With Inflammation and Lipid Peroxidation.

IntroductionCigarette smoking promotes angiotensin-converting enzyme (ACE) production and causes a substantial change in inflammation and oxidative stress, resulting in an increase in antioxidant activity and lipid peroxidation.ObjectiveThe study's goal is to determine the role of cigarette smoking on serum ACE and its relation with inflammatory markers and lipid peroxidation.MethodsThe cross-sectional study consists of three groups. The study participants are all men between the age group of 20 to 55 years. Group 1 includes 120 healthy controls as nonsmokers, Group 2 consists of 120 active smokers with coronary heart disease (CHD) and Group 3 includes 120 active smokers with diabetic CHD patients attending the SRM Medical College Hospital in Tamil Nadu for cardiology and medical Outpatient. Measurements of serum ACE, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein (hsCRP), and matrix metalloprotease-9 (MMP-9) were performed using the ELISA method (enzyme-linked immunosorbent assay). Using a spectrophotometric approach, the total antioxidant capacity and lipid peroxidation, particularly Malondialdehyde (MDA), were assessed.ResultsThe mean serum ACE (92.35±10.28), oxLDL (48.59±8.56), hs-CRP (5.87±1.62), MMP-9 (89.20±30.19), and MDA (1.146±0.198) levels were significantly (p-value <0.0001) higher in smokers with CHD and diabetes (group 3) when compared to group 1 and group 2. On the other hand, the total antioxidant capacity (0.413±0.097) of smokers of group 3 was found to be (p<0.0001) significantly lower than those of group 1 and group 2. The study also demonstrated a significant correlation between ACE with MDA, ox-LDL, total antioxidant capacity, hs-CRP, MMP-9, smoking load, and smoking intensity in smokers.ConclusionThe study concludes a substantial correlation exists in smokers owing to ACE modification, which results in inflammation and lipid peroxidation activation. This is strongly associated with an increased risk of major cardiovascular events.

Coronary computed tomography angiography as a screening tool for moderate-high risk asymptomatic type 2 diabetes mellitus patients.

BackgroundThere are few data on the clinical significance of coronary computed tomography angiography (CCTA) in asymptomatic type 2 diabetes mellitus (T2DM) patients. We performed a retrospective study to evaluate coronary heart disease (CHD) screening in asymptomatic patients with T2DM using CCTA and CHD risk stratification prediction.Materials and methodsData from 141 T2DM patients (58 ± 8 years, 57% males) without known symptoms suggestive of CHD who underwent CCTA were retrospectively analyzed. The patients were classified into three subgroups based on United Kingdom prospective diabetes study (UKPDS) CHD risk stratification prediction. Seventy-four patients without diabetes mellitus and CHD who underwent CCTA successively were chosen as the control group. The segment involvement score (SIS), segment stenosis score (SSS), stenosis coefficient (SC), severe proximal plaque (SPP) positive ratio and CCTA-adapted Leaman score (CT-LeSc) based on CCTA data were evaluated and compared among the groups.ResultsCompared with the patients in the control group, patients in the moderate-high risk DM groups had higher scores on the SIS, SSS, SC, CT-LeSc, and a higher SPP positive ratio (all p-values < 0.001), and no difference was observed between the low-risk group and the control group (p = 0.136, p = 0.088, p = 0.0.067, p = 0.225, p = 1.000, respectively). Compared with patients in the control group, the patients in the moderate-high risk DM groups had increased odds of SIS > 3 [odds ratio (OR) = 6.557, p < 0.001; OR = 4.455, p < 0.001, respectively], SSS > 5 (OR = 5.727, p < 0.001; OR = 5.144, p < 0.001, respectively), CT-LeSc > 8.7 (OR = 3.780, p = 0.001; OR = 2.804, p = 0.007, respectively), and obstructive stenosis (OR = 7.233, p < 0.001; OR = 5.787, p < 0.001, respectively).ConclusionThe moderate-high CHD risk patients had increased odds of obstructive coronary artery stenosis, and the distribution of coronary artery stenosis was more extensive and more severe in that group compared to the patients without diabetes mellitus and CHD. CHD can be effectively screened in moderate-high risk asymptomatic T2DM patients using CCTA.

A Study on Prediction of Diabetic Coronary Heart Disease Using Machine Learning Algorithms

One of the most prevalent illnesses in today's fast-paced culture is coronary heart disease in people with diabetes. It is challenging to foresee the onset of diabetic heart disease, a chronic ailment that affects people all over the world. One common misconception about machine learning is that it is an inaccessible field of study reserved for nerdy academics. However, concerning accuracy to predict disease based on symptoms, many studies have turned to machine learning methods, and this study provides a comparative analysis of these methods appeared in published research articles. This paper takes a close look at the research into predicting diabetic coronary artery disease using machine learning techniques, as well as the many different combinations of learning algorithms that have been employed to do so.

Serum metabolic profile analysis of syndrome of Qi-yin deficiency and Yang deficiency in diabetic coronary heart disease by UPLC-Q/TOF MS

AimsQi-yin deficiency (QYD) and Yang-deficiency (YD) syndrome are two common syndromes with contrasting clinical manifestations of low fever and cold phobia. Different syndrome phenotypes must have distinct biological underpinnings in vivo. Based on serum metabolomics, this study aims to reveal the biological characteristics of the two diabetic coronary heart disease syndromes mentioned above. MethodsA total of 33 diabetic coronary heart disease (DCHD) patients were included in the study, with 13 cases of QYD, 11 cases of YD syndrome, and 9 cases of Pinghe constitution (PH). Based on UPLC-Q/TOF MS, metabolomics was used to detect and analyze serum samples from the three groups mentioned above. To find differentiating metabolites, PLS-DA (Partial least squares discrimination analysis) and database searching were used. Meanwhile, the metabolic pathways of various metabolites were investigated. ResultsThere were 17 different metabolites between QYD syndrome and YD syndrome of DCHD. Cyclic GMP, LysoPE (20:3), proline, isoleucine, N-lactoyl-tyrosine, 3-oxohexadecanoyl-CoA, and oxalosuccinic acid were lower in the (YD) group than those in the PH group, while galactitol, N-lactoyl-tyrosine, and oxalosuccinic acid were higher in the QYD group than in the PH group. The 17 differential metabolites mentioned above were linked to a variety of pathways, including amino acid metabolism, purine metabolism, fatty acid elongation in mitochondria, the tricarboxylic acid cycle, lipid metabolism, energy metabolism, etc. ConclusionDifferent DCHD syndromes, such as liver-kidney Yin deficiency and YD syndrome, have different biological bases for the same disease. To some extent, the findings of this study provide a scientific foundation for different approaches to treating the same disease in Traditional Chinese Medicine. It is also important for guiding the clinical use of herbal medicine.

Abstract 13296: Bivalirudin versus Unfractioned Heparin in Patients With Diabetes Mellitus Undergoing Elective Percutaneous Coronary Intervention: Results at One Year

Introduction: Patients with Diabetes Mellitus (DM) and coronary heart disease have high risk in bleeding and thrombotic events. However, data on safety and effectiveness of bivalirudin in patients with DM undergoing elective percutaneous coronary intervention (PCI) are lacking which needs further scientific research. Methods: 1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10250 patients anticoagulated with unfractioned heparin (UFH) were performed propensity score matching at 1:4 ratio. Finally, 376 (bivalirudin group) and 878 (UFH with or without glycoprotein IIb/IIIa inhibitors [GPI] group)patients with DM were enrolled respectively. The safe endpoints were according to the Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding and BARC 3 or 5 bleeding. The effective endpoint was major adverse cardiac and cerebrovascular events (MACCE), including death, MI, revascularization, stent thrombosis and stroke. Results: During one-year follow-up, multivariate Cox analysis showed there was no significant difference in the risk of BARC 2,3 or 5 bleeding (P=0.451) and BARC 3 or 5 bleeding (P=0.124) between bivalirudin group and UFH with or without GPI group. As for MACCE, there was no significant difference between bivalirudin group and UFH with or without GPI group (P=0.153). Moreover, there was a reduction in the risk of MI between bivalirudin group and UFH with or without GPI group (HR:0.199, 95%CI: 0.047-0.845, P=0.029) but no significant difference in the risk of death, revascularization, stent thrombosis or stroke (all P&gt;0.05). Conclusions: Although DM is considered a high risk factor for bleeding and thrombotic events, compared with UFH with or without GPI, bivalirudin reduced the risk of MI in patients with DM undergoing elective PCI and did not increase the risk of MACCE, while the risk of bleeding was similar in two groups.

Application Analysis of Predictive Nursing Model in Elderly Patients with Diabetic Coronary Heart Disease

Application Analysis of Predictive Nursing Model in Elderly Patients with Diabetic Coronary Heart Disease

Clinical Study of Danshen Dripping Pills in Treating Diabetic Coronary Heart Disease

Clinical Study of Danshen Dripping Pills in Treating Diabetic Coronary Heart Disease

Postprandial plasma glucose excursion is associated with an atherogenic lipid profile in individuals with type 2 diabetes mellitus: A cross-sectional study.

Coronary heart disease (CHD) is a prevalent complication of type 2 diabetes mellitus (T2DM). The atherogenic low-density lipoprotein (LDL) cholesterol is an established risk factor of cardiovascular disease, and evidence also suggests that postprandial plasma glucose (PPG) levels closely delineate CHD mortality in diabetes. The investigators hypothesized that postprandial plasma glucose excursion (PPGE), defined as the difference between 2-hour PPG and fasting plasma glucose (FPG), may be associated with plasma LDL cholesterol levels in patients with T2DM. This study enrolled diabetic participants for whom FPG and lipid profile were sampled after a 12-hour fast, followed by PPG sampling two hours after consuming a standard meal with 75 grams of carbohydrates. The study enrolled 379 participants who were divided into PPGE tertiles according to the difference between their 2-hour PPG and FPG. Participants in the highest PPGE tertile had considerably greater plasma LDL cholesterol levels than patients in the lowest tertile (126.7 mg/dL vs. 99.5 mg/dL, P <0.001). Linear regression analysis also demonstrated that the PPGE was positively correlated with plasma LDL cholesterol levels (β coefficient: 0.165, P < 0.001). Postprandial glucose excursion positively correlated with plasma LDL cholesterol levels in individuals with T2DM. Participants with raised PPGE harbored greater LDL cholesterol levels than those with lower postprandial glucose fluctuations. Therefore, postprandial glucose excursion is associated with an atherogenic lipid profile and may be a modifiable risk factor of diabetic CHD.

A pragmatic randomised controlled trial referring to a Personalised Self-management SUPport Programme (P-SUP) for persons enrolled in a disease management programme for type 2 diabetes mellitus and/or for coronary heart disease

BackgroundType 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) are two chronic diseases that cause a tremendous burden. To reduce this burden, several programmes for optimising the care for these diseases have been developed. In Germany, so-called disease management programmes (DMPs), which combine components of Disease Management and the Chronic Care Model, are applied. These DMPs have proven effective. Nevertheless, there are opportunities for improvement. Current DMPs rarely address self-management of the disease, make no use of peer support, and provide no special assistance for persons with low health literacy and/or low patient activation. The study protocol presented here is for the evaluation of a programme that addresses these possible shortcomings and can be combined with current German DMPs for T2DM and CHD. This programme consists of four components:Meetings of peer support groupsPersonalised telephone-based health coaching for patients with low literacy and/or low patient activationPersonalised patient feedbackA browser-based web portalMethodsStudy participants will be adults enrolled in a DMP for T2DM and/or CHD and living in North Rhine-Westphalia, a state of the Federal Republic of Germany. Study participants will be recruited with the assistance of their general practitioners by the end of June 2021. Evaluation will be performed as a pragmatic randomised controlled trial with one intervention group and one waiting control group. The intervention group will receive the intervention for 18 months. During this time, the waiting control group will continue with usual care and the usual measures of their DMPs. After 18 months, the waiting control group will also receive a shortened intervention. The primary outcome is number of hospital days. In addition, the effects on self-reported health-state, physical activity, nutrition, and eight different psychological variables will be investigated. Differences between values at month 18 and at the beginning will be compared to judge the effectiveness of the intervention.DiscussionIf the intervention proves effective, it may be included into the DMPs for T2DM and CHD.Trial registrationThe study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) in early 2019 under the number 00020592. This registry has been affiliated with the WHO Clinical Trials Network (https://www.drks.de/drks_web/setLocale_EN.do) since 2008. It is based on the WHO template, but contains some additional categories for which information has to be given (https://www.drks.de/drks_web/navigate.do?navigationId=entryfields&messageDE=Beschreibung%20der%20Eingabefelder&messageEN=Description%20of%20entry%20fields ). A release and subsequent number assignment only take place when information for all categories has been given.

Network Pharmacological Study and Molecular Docking Analysis of Qiweitangping in Treating Diabetic Coronary Heart Disease.

Background Coronary heart disease (CHD) is one of the most important complications of diabetes mellitus, having a high disability fatality rate. Qiweitangping is a Chinese medicine to control diabetes (type 1 and type 2 diabetes) and complications, having been used in clinic for more than 20 years, with the expected therapeutic effect. In a previous clinical study, the total effective rate of the drug for the treatment of type 2 diabetes reached 92.7%. However, the mechanism of the treatment process is unclear. Therefore, this research was conducted to explore the mechanism of treating diabetic coronary heart disease with the assistance of bioinformatics methods. Methods The TCMSP database was used to collect the effective chemical constituents of Qiweitangping and the target genes of the chemical constituents, and the related genes of diabetic CHD were obtained from the GeneCard database. Furthermore, the intersection was found between the target gene of the drug and the related gene of the disease to obtain the candidate genes; the STRING database and DAVID database were used to perform protein interaction analysis and KEGG enrichment analysis on the candidate genes. Also, molecular docking was used for auxiliary verification. Finally, a “drug component-gene target-pathway” network was constructed by using Cytoscape software. Results Sixty-two effective chemical components including naringin, diosgenin, formogenin, isorolin, and isocryptanshinone, fifty-nine candidate target genes (such as AKT1, CASP3, and VEGF-A), and thirty-nine related pathways in Qiweitangping were obtained. In addition, two pairs (CASP-naringenin and STAT3-cryptotanshinone) of molecular docking results showed good affinity (<−5.00 kcal/mol). Conclusion The results of the study indicate that Qiweitangping treats diabetic CHD with multiple chemical components. Its mechanism of action may be related to the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and ErbB signaling pathway. STAT3 and CASP genes have been verified by molecular docking to have a relatively good combination with Qiweitangping. This study is the theoretical basis for further experimental study on the treatment mechanism of diabetic CHD with Qiweitangping.

Endothelial microparticle-associated protein disulfide isomerase increases platelet activation in diabetic coronary heart disease.

Background: Endothelial microparticles (EMPs) carrying the protein disulfide isomerase (PDI) might play a key role in promoting platelet activation in diabetes. This study aimed to examine the activation of platelets, the amounts of MPs, PMPs, and EMPs, and the concentration and activity of PDI in patients with diabetic coronary heart disease (CHD) and non-diabetic CHD.Methods: Patients with CHD (n=223) were divided as non-diabetic CHD (n=121) and diabetic CHD (n=102). Platelet activation biomarkers, circulating microparticles (MPs), the concentration of protein disulfide isomerase (PDI), and MP-PDI activity were determined. The effect of EMPs on platelet activation was investigated in vitro. Allosteric GIIb/IIIa receptors that bind to PDI were detected by a proximity ligation assay (PLA).Results: Platelet activation, platelet-leukocyte aggregates, circulating MPs, EMPs, PDI, and MP-PDI activity in the diabetic CHD group were significantly higher than in the non-diabetic CHD group (P<0.05). Diabetes (P=0.006) and heart rate <60 bpm (P=0.047) were associated with elevated EMPs. EMPs from diabetes increased CD62p on the surface of the platelets compared with the controls (P<0.01), which could be inhibited by the PDI inhibitor RL90 (P<0.05). PLA detected the allosteric GIIb/IIIa receptors caused by EMP-PDI, which was also inhibited by RL90.Conclusions: In diabetic patients with CHD, platelet activation was significantly high. Diabetes and heart rate <60 bpm were associated with elevated EMPs and simultaneously increased PDI activity on EMP, activating platelets through the allosteric GPIIb/IIIa receptors.

Design and Methodology of a Multicenter Randomized Clinical Trial to Evaluate the Efficacy of Tongmai Jiangtang Capsules in Type 2 Diabetic Coronary Heart Disease Patients.

Background: Population-based studies have consistently showed an increased incidence of coronary heart disease and cardiac mortality in patients with type 2 diabetes mellitus (T2DM). Tongmai Jiangtang capsules (TJC) are Chinese patent medicines that have been approved in China for the treatment of diabetic vascular complications. However, the evidence supporting the efficacy of Tongmai Jiangtang capsules in type 2 diabetic coronary heart disease (T2DM-CHD) remains unclear. Herein, we designed a randomized, parallel-controlled clinical trial to investigate a new complementary therapy for T2DM-CHD patients. Methods: A total of 360 T2DM-CHD subjects (aged 18–75 years) will be randomly assigned to the TJC group or the placebo group at a 2:1 ratio. On the basis of western medicine therapy, all the participants will receive TJC or placebo, orally, three capsules/treatment, three per day for 12 weeks. The primary outcomes will be assessed according to the Canadian Cardiovascular Society (CCS) classification. All statistical analyses will be performed setting a two-sided 0.05 significance level, using SAS 9.4 statistical software. Discussion: The efficacy of TJC for the treatment of T2DM-CHD patients will be evaluated. The study will provide reliable clinical research evidence for application of TJC in treating T2DM-CHD patients. Clinical Trial Registration: https://www.chictr.org.cn/enIndex.aspx, Chinese Clinical Trial Registry ChiCTR2000037491.