Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes

BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as insulin resistance,systematic inflammation,and oxidative stress,and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis.AIM To investigate the association between myosteatosis and coronary artery calcification(CAC)in patients with T2DM.METHODS Patients with T2DM,who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography(CT)scans,were included.The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level.The CAC score was determined from thoracic CT images using the Agatston scoring method.Myosteatosis was diagnosed according to Martin’s criteria.Severe CAC(SCAC)was defined when the CAC score exceeded 300.Logistic regression and decision tree analyses were performed.RESULTS A total of 652 patients with T2DM were enrolled.Among them,167(25.6%)patients had SCAC.Logistic regression analysis demonstrated that myosteatosis,age,duration of diabetes,cigarette smoking,and alcohol consumption were independent risk factors of SCAC.Myosteatosis was significantly associated with an increased risk of SCAC(OR=2.381,P=0.003).The association between myosteatosis and SCAC was significant in the younger patients(OR=2.672,95%CI:1.477-4.834,P=0.002),but not the older patients(OR=1.456,95%CI:0.863-2.455,P=0.188),and was more prominent in the population with lower risks of atherosclerosis.The decision tree analyses prioritized older age as the primary variable for SCAC.In older patients,cigarette smoking was the main contributing factor for SCAC,while in younger patients,it was myosteatosis.CONCLUSION Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM,especially in the population with younger ages and fewer traditional risk factors.

Nε-carboxymethyl-lysine and inflammatory cytokines,markers and mediators of coronary artery disease progression in diabetes

This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients

Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Ideal Cardiovascular Health Metrics and Coronary Artery Calcification in Northern Chinese Population:A Cross-sectional Study

Objective Coronary artery calcification（CAC） is a well-established risk predictor of coronary heart disease events and is recognized as an indicator of subclinical atherosclerosis.Methods A cross-sectional study consisting of 2999 participants aged ≥40 years from the Jidong community of Tangshan City,an industrial and modern city of China,was conducted between 2013 and 2014 to examine the association between the ideal cardiovascular health（CVH） metrics and CAC.The ideal CVH metrics were determined based on the definition of the American Heart Association（AHA）.The participants were then grouped into 4 categories according to the quartiles of their CVH metric scores as follows：first quartile（0-2）,second quartile（3）,third quartile（4）,and fourth quartile（5-7）.CAC was assessed by using high-pitch dual-source CT,and patients were identified based on thresholds of 0,10,100,or 400 Agatston units,as per common practice.Results The prevalence of subclinical atherosclerosis was 15.92%,13.85%,6.76%,and 1.93%,determined by using the CAC scores at thresholds of 0,10,100,and 400 Agatston units,respectively.Compared with the group in the first quartile,the other three CVH groups had a lower odds ratio of CAC 0 after adjusting for age,sex,income level,education level,and alcohol use in the logistic regression analysis.The odds ratios in these groups were 0.86 [95% confidence interval（CI）,0.63-1.17;P0.05],0.75（95% CI,0.55-1.02;P0.05）,and 0.49（95% CI,0.35-0.69;P0.05）,respectively.These associations of CAC with the CVH metrics were consistent when different CAC cutoff scores were used（0,10,100,or 400）.Conclusion The participants with more-ideal cardiovascular metrics had a lower prevalence of subclinical atherosclerosis determined according to CAC score.Maintaining an ideal cardiovascular health may be valuable in the prevention of atherosclerosis in the general population.

Discovering hidden patterns:Association rules for cardiovascular diseases in type 2 diabetes mellitus

BACKGROUND It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus(T2DM)and coronary artery disease(CAD),and studies are able to correlate their relationships with available biological and clinical evidence.The aim of the current study was to apply association rule mining(ARM)to discover whether there are consistent patterns of clinical features relevant to these diseases.ARM leverages clinical and laboratory data to the meaningful patterns for diabetic CAD by harnessing the power help of data-driven algorithms to optimise the decision-making in patient care.AIM To reinforce the evidence of the T2DM-CAD interplay and demonstrate the ability of ARM to provide new insights into multivariate pattern discovery.METHODS This cross-sectional study was conducted at the Department of Biochemistry in a specialized tertiary care centre in Delhi,involving a total of 300 consented subjects categorized into three groups:CAD with diabetes,CAD without diabetes,and healthy controls,with 100 subjects in each group.The participants were enrolled from the Cardiology IPD&OPD for the sample collection.The study employed ARM technique to extract the meaningful patterns and relationships from the clinical data with its original value.RESULTS The clinical dataset comprised 35 attributes from enrolled subjects.The analysis produced rules with a maximum branching factor of 4 and a rule length of 5,necessitating a 1%probability increase for enhancement.Prominent patterns emerged,highlighting strong links between health indicators and diabetes likelihood,particularly elevated HbA1C and random blood sugar levels.The ARM technique identified individuals with a random blood sugar level>175 and HbA1C>6.6 are likely in the“CAD-with-diabetes”group,offering valuable insights into health indicators and influencing factors on disease outcomes.CONCLUSION The application of this method holds promise for healthcare practitioners to offer valuable insights for enhancing patient treatment targeting specific subtypes of CAD with diabetes.Implying artificial intelligence techniques with medical data,we have shown the potential for personalized healthcare and the development of user-friendly applications aimed at improving cardiovascular health outcomes for this high-risk population to optimise the decision-making in patient care.

Coronary artery calcification in chronic kidney disease:An update

Arterial calcification is a well-recognized complication of advanced atherosclerosis.Chronic kidney disease(CKD) is characterized by significantly more pronounced,dis-seminated and fast-progressing calcification of the vascular system,including the coronary arteries.New computed tomography-based imaging techniques al-low for the noninvasive assessment and monitoring of calcification in different vascular sites.Coronary artery calcification(CAC) develops early in the course of CKD and is tightly associated with mineral and bone disor-ders,which include but are not limited to secondary hyperparathyroidism.In this review,recent data on the pathogenesis of CAC development and progression are discussed,with a special emphasis on fibroblast growth factor 23 and its co-receptor,klotho.The prevalence,progression and prognostic significance of CAC are reviewed separately for patients with end-stage renal disease treated with dialysis,kidney transplant recipi-ents and patients with earlier stages of CKD.In the last section,therapeutic considerations are discussed,with special attention paid to the importance of treatment that addresses mineral and bone disorders of CKD.

Current understanding of coronary artery calcification

冠的动脉石灰化(CAC ) 在有冠的心疾病(CHD ) 的病人是高度流行的并且与主要不利心血管的事件被联系。有 CAC&#x02014 的二种公认的类型；他们的内层、中间的石灰化，和各个有特定的风险因素。关于脉管的石灰化的机制的几个理论被提出了，并且我们当前相信脉管的石灰化是一个活跃、调整过程。CAC 能通常与严重 CHD，和这无征状的现象在病人被发现使 CAC 的早诊断重要。冠的计算 tomographic angiography 是主要 noninvasive 工具检测钙化的损害。由得分的冠的动脉石灰化的测量是为在在中间的风险的无征状的成年人的心血管的风险评价的一个合理度量标准。迄今为止， CAC 的有效医疗没被识别。经皮的冠的干预的几策略与 CAC，但是与不能令人满意的结果被用于 CHD 病人。CAC 的预后仍然是 CHD 病人的一个主要问题。因此，关于 CAC 的机制的更多的细节需要被阐明以便改进 CAC 的理解和治疗。

Coronary artery disease in Chinese adults with type 2 diabetes mellitus estimated by electron beam computed tomography and electron beam computed tomography angiography

Objective To assess the prevalence and risk of coronary artery disease(CAD) in Chinese adults with type 2 diabetes mellitus(T2DM) using electron beam computed tomography(EBCT) and EBCT angiography(EBCTA) . Methods:Ninety-four cases were enrolled in this study including diabetes(n=28) ,impaired glucose tolerance(IGT,n=30) ,coronary heart disease(CHD,n=11) ,and control(n=25) . Cardiac EBCT plain scanning and EBCTA were performed on all of these subjects to evaluate coronary artery calcifica-tion(CAC) scores,and number of segments of stenosed coronary arteries. Both CAC and/or coronary artery stenosis were defined as patients with coronary artery lesions(CAL) . Results CAC scores were not different with the control,diabetes,IGT,or CHD(P>0.05) groups. Compared to control(0.520±1.295) ,more stenosed coronary arteries segments(P<0.05) were detected in diabetes(2.964± 1.915) ,IGT(2.200±2.024) ,and CHD(2.273±1.679) . Number of stenosed artery segments were correlated with age(r=0.215,P=0.019) ,postprandial glucose(r=0.224,P=0.015) ,total cholesterol(r=0.323,P=0.000) ,and duration of diabetes(r=0.208,P=0.004) . The incidences of CAL in diabetes(96.43%) ,IGT(93.33%) ,and CHD(90.91%) was substantially higher than that in normal control(56.00%,P<0.01) . The odds ratio of CAL associated with having diabetes was estimated to be 7.514(95% CI:1.885-63.778) . Conclusions Coronary artery lesions are prevalent in Chinese adults with type 2 diabetes,implying a high CAD risk. EBCTA holds potential in depicting the details of CAL and can be used to track the progression of CAD in diabetes patients.

Paraoxonase 1 gene (Gln¹⁹²-Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups;Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.

Positive correlation between plasma PCSK9 and tissue factors levels in patients with angiographically diagnosed coronary artery disease and diabetes mellitus

(PCSK9 )BackgroundPro 蛋白质 convertase subtilisin/kexin 类型 9 是影响低密度的脂蛋白胆固醇(LDL-C ) 的血浆层次的分泌蛋白质。氧化 LDL 和织物因素(TF ) 贡献了 prothrombotic 状态的发展。探索在血浆之间的关系的现在的学习目的与冠的动脉疾病(CAD ) 在病人 PCSK9 和 TF 的铺平 .MethodsFrom 2013 年 7 月到 2014 年 3 月，我们注册了因为怀疑的 CAD，在这研究在北京 Anzhen 医院经历了冠的 angiography 的 197 个连续病人。所有病人没有使用类脂化合物阴沉的药的历史。这 197 个病人(131 男性和 66 女性，意味着年龄 56.9 &#x000b1；11.8 年) ， 81 angiographically 诊断了 CAD。临床的数据是镇定的。血浆 PCSK9 和 TF 用连接酶的 immunosorbent 试金(ELISA ) 被测量。血浆 PCSK9 和 TF 的层次被比较，他们的关联在 PCSK9 的不同耐心的 groups.ResultsBoth 血浆层次之中分析了(279.8 &#x000b1；60.4 &#x000b5； g/L 对 216.5 &#x000b1；45.3 &#x000b5； g/L， P &#x0003c；0.01 ) 并且 TF (156.4 &#x000b1；26.6 &#x000b5； g/mL 对 112.1 &#x000b1；38.3 &#x000b5； g/L， P &#x0003c；0.01 ) 在有 CAD 的病人是显著地更高的，作为与那些相比没有 CAD。关联分析证明 PCSK9 的血浆水平显著地有或没有 CAD 在两个病人与 TF 的被相关。然而，在调整以后的 multivariate 回归分析好久，性，吸烟，酒精，高血压和 hyperlipidemia 与类型 2 糖尿病 mellitus 仅仅在 CAD 病人显示出那，在 PCSK9 和 TF 的血浆层次之间有重要积极关联(&#x003b2；= 0.353， P &#x0003c；0.01 ) 没有糖尿病 mellitus， PCSK9 的 .ConclusionsThe 血浆水平独立地并且断然与糖尿病 mellitus 在 CAD 病人，然而并非在那些与 TF 的被联系。进一步的学习被需要调查内在的机制。

Association between Hepato-Biliary Status and HbA1C in Type 2 Diabetes Mellitus with Coronary Artery Disease (CAD)

Bilirubin has both antioxidant activity and cardioprotective potential. Decreased levels are associated with predicting CAD. Recent studies showed that bilirubin has inverse correlation with glycemic status. So in this we evaluated the role of Hepatobiliary function as a marker of predictor CAD in patient with T2DM. Total 100 subjects included 50 T2DM patients with CAD and 50 T2DM without CAD. All the subject venous blood was collected after overnight fasting for biochemical analysis. After the statistical analysis, the results showed significant difference between two groups as follows total bilirubin (0.32 ± 0.15;0.90 ± 032;p = 0.000), direct bilirubin, indirect bilirubibn, Total Protein, Albumin, ALT, AST, HbA1c. Our finding implies that decreased serum bilirubin increases the risk of CAD in patients with T2DM and it shows inverse correlation between HbA1c and bilirubin.

Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

编码 adiponectin 受体 1 的基因( ADIPOR1 )和小象ubiquitin一样修饰词( SUMO4 ) 4 被连接了到 anti-atherogenic 效果，但是很少对是否被知道在二基因的多型性，独立行动或交往，没有 diabetes.MethodsWe genotyped ，影响冠的动脉疾病( CAD )的风险没有糖尿病的 200 个 CAD 病人和没有 CAD 的 200 控制，它被选择基于前一个没有 diabetes.ResultsRisk 等位基因，协会也是的潜力在 ADIPOR1 (rs7539542-G， rs7514221-C 和 rs3737884-G ) 在三 SNP 在这些 SNP 和 CAD 的临床的特征之间探索了，没有糖尿病，在在 SUMO4 的 SNP rs237025 的 G 等位基因显著地增加了 CAD 的风险，与从 1.79 ～ 4.44 的 ORs。任何这四风险等位基因的搬运人出现了类似不利 ? 临床的特征。与有 CC 或 GC 遗传型的个人相比，有在 rs3737884 的 GG 遗传型的那些在影响了左前面的下降冠的动脉的 CAD 的显著地更高的风险(或：6.77， P = 0.009 ) ，恰好冠的动脉(或：4.81， P = 0.028 ) 或容器的一个相对大的数字(P = 0.04 ) 。没有糖尿病，在 SUMO4 在 SNP 象风险等位基因一样在 ADIPOR1 在三 SNP 中的至少一个带风险等位基因的个人比不带任何风险等位基因的个人在 CAD 的显著地更高的风险(或：5.82， 95% CI：1.2327.7， P = 0.013 ) 没有糖尿病，在 ADIPOR1 和 SUMO4 的 .ConclusionsSNPs 与 CAD 的提高的风险被联系，并且在二基因的 SNP 可以交往联合影响疾病风险。

Clinical evaluation of Technetium-99m sestamibi myocardial perfusion SPECT in diabetes with suspected coronary artery diseases

Objective:To study the clinical value of Technetium-99m sestamibi myocardial perfusion single photon emission computed tomography(SPECT) in diabetes with suspected coronary artery diseases.Methods:Seventy-eight diabetic patients complicated with cardiac symptoms or electrocardiogram(ECG) abnormalities and suspected coronary heart disease hospitalized in the department of endocrinology from January,2008 to December,2008 were investigated.Technetium-99m sestamibi myocardial perfusion SPECT was performed in all patients.Exercise stress test was done in 35 cases(group A).Adenosine stress test was done in 43 cases(group B).Results:The positive rates in the two groups were 54.29%(19/35) and 53.48%(23/43),respectively.There was no statistic difference between the 2 groups(P>0.05).The abnormality rates in male and female groups were 63.04% and 28.13%,respectively(P<0.01).Eighty-six segments of perfusion abnormality were detected in 38 positive patients.Four segments of fixed defect were found in 4 cases.Conclusion:As non-invasive method,myocardial perfusion SPECT can play an important role in the treatment of diabetes with suspected coronary artery disease.

Can Ophthalmoscope Predict Silent Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus?

Background & Aim: Diabetic retinopathy (DR) and Coronary Artery Disease (CAD) share similar pathophysiological background of vascular damage. So we aimed to study the relationship between DR and silent CAD in patients with type 2 diabetes mellitus (T2DM). Subject & Methods: A cross sectional study was performed on 40 patients with T2DM from diabetic outpatient clinic in Ain Shams University Hospitals, Cairo, Egypt from June 2012 to December 2012. All patients were subjected to data collection, laboratory analysis and imaging studies. Patients with known CAD, abnormal resting or stress ECG, abnormal ejection fraction or segmental wall motion abnormalities, smoking history, hypertension, or abnormal lipid profile were excluded. Results: Mean age is 62.35 ± 1.38 years, 75% (n = 30) were females, 75% (n = 30) had DR, and 77.50% (n = 31) had positive Tc99 scan. There is a significant positive association between Tc99 scan and DR (p value = 0.029) as 86.7% of patients with DR had positive Tc99 scan. Resting and stress perfusion TC99 scan were significantly worse (91.77% vs 100%;86.48% vs 96.27%, p value = 0.008, 0.005 respectively) and microalbuminuria were significantly higher (207 ± 29.65 vs 36 ± 10.66 mg/dl, p value =< 0.001) in patients with DR. By binary logistic regression, DR was an independent predictor for CAD (OR was 16.377, 95% CI was 1.017 - 263.586, p value = 0.049) after adjustment of SBP and albuminuria. Conclusion: DR is an independent predictor of asymptomatic CAD even with normal stress ECG and echocardiography. Routine screening for CAD using Tc99 scan is recommended in patients with DR even if asymptomatic. More multi-centric prospective studies are needed to elucidate the effect of the degree of DR on CAD risk.

Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease:Prospective cohort study and genetic analyses

Background:While type 2 diabetes mellitus(T2DM)is considered a putative causal risk factor for coronary artery disease(CAD),the intrinsic link underlying T2DM and CAD is not fully understood.We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods:We evaluated phenotypic associations using data from the United Kingdom Biobank(N=472,050).We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM,with and without adjustment for body mass index(BMI)(T2DM:N_(case)/N_(control)=74,124/824,006;T2DM adjusted for BMI[T2DM_(adj)BMI]:N_(case)/N_(control)=50,409/523,897)and for CAD(N_(case)/N_(control)=181,522/984,168).We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM(N_(case)/N_(control)=180,834/1,159,055).Results:Observational analysis suggested a bidirectional relationship between T2DM and CAD(T2DM→CAD:hazard ratio[HR]=2.12,95%confidence interval[CI]:2.01–2.24;CAD→T2DM:HR=1.72,95%CI:1.63–1.81).A positive overall genetic correlation between T2DM and CAD was observed(r_(g)=0.39,P=1.43×10^(-75)),which was largely independent of BMI(T2DM_(adj)BMI–CAD:r_(g)=0.31,P=1.20×10^(–36)).This was corroborated by six local signals,among which 9p21.3 showed the strongest genetic correlation.Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci.Mendelian randomization analysis supported a bidirectional causal relationship(T2DM→CAD:odds ratio[OR]=1.13,95%CI:1.11-1.16;CAD→T2DM:OR=1.12,95%CI:1.07-1.18),which was confirmed in multiancestry individuals(T2DM→CAD:OR=1.13,95%CI:1.10-1.16;CAD→T2DM:OR=1.08,95%CI:1.04-1.13).This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,with mediation proportions of 54.1%(95%CI:24.9-83.4%)and 90.4%(95%CI:29.3-151.5%),respectively.Conclusion:Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Coronary microvascular dysfunction in diabetes mellitus:A review

The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arteries.These data are confirmed in diabetic animal mod-els,where lesions of small coronary arteries have been described.These concepts are epitomized in the classic microvascular complications of diabetes,i.e.blindness,kidney failure and distal dry gangrene.Most importantly,accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility.This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes,and assesses the current state of knowledge regarding the triggers for inflammation in this disease.We evaluate the roles of hyperglycemia,oxidative stress,polyol pathway,protein kinase C,advanced glycation end products,insulin resistance,peroxisome proliferator-activated receptor-γ,inflammation,and diabetic cardiomyopathy as a "stem cell disease".Furthermore,we discuss the mechanisms responsible for impaired coronary arteriole function.Finally,we consider how new insights in diabetes may provide innovative therapeutic strategies.

Coronary angiography in the very old: impact of diabetes on long-term revascularization and mortality

Background Diabetes is often associated with coronary artery disease,leading to adverse clinical outcomes.Real-world data is limited regarding the impact of diabetes in very old patients undergoing coronary angiography on the risk for late or repeated coronary revascularization and mortality.Methods Retrospective analysis of 1,353 consecutive patients>80 years who were admitted to the cardiac unit and further underwent coronary angiography.Subsequent revascularization procedures and all-cause mortality were recorded over a median fbllow-up of 47 months and their relation to diabetic status and presentation with acute coronary syndrome(ACS)was studied.Results Diabetes was present in 31%of the patients undergoing coronary angiography,and was associated with higher rates of obesity,hypertension,hyperlipidemia,chronic kidney disease and female gender.ACS was the presenting diagnosis in 71%of the patients and was associated with worse survival(1-year mortality 20%in ACS vs.6.2%in non-ACS patients,P<0.0001).Increase in long-term mortality rates was seen in diabetic subjects compared to non-diabetic subjects presenting with ACS(log-rank P=0.005),but not in the non-ACS setting(P=0」99).In a multivariable model,additionally adjusting for acuity of presentation,the presence of diabetes was associated with an adjusted hazard ratio of 1.60(95%confidence interval:12-2.28),P=0.011,for the need of late or repeat coronary revascularization and 1.48(1.26-1.74),P<0.0001 for all-cause mortality,during long-term follow-up.Conclusions In very old patients undergoing coronary angiography,presentation with ACS was associated with worse survival.Diabetes was an independent predictor of late or repeated revascularization and long-term mortality.

Inflammatory markers,oxidative stress,and mitochondrial dynamics:Repercussions on coronary artery disease in diabetes

Inflammatory markers and mediators that affect the development of cardiovascular diseases have been the focus of recent scientific work.Thus,the purpose of this editorial is to promote a critical debate about the article titled“Nε-carboxymethyl-lysine and inflammatory cytokines,markers,and mediators of coronary artery disease progression in diabetes”,published in the World Journal of Diabetes in 2024.This work directs us to reflect on the role of advanced glycation end products,which are pro-inflammatory products arising from the metabolism of fatty acids and sugars whose main marker in tissues is Nε-carboxymethyllysine(NML).Recent studies have linked high levels of pro-inflammatory agents with the development of coronary artery disease(CAD),especially tumor necrosis factor alpha,interleukins,and C-reactive protein.These inflammatory agents increase the production of reactive oxygen species(ROS),of which people with diabetes are known to have an increased production.The increase in ROS promotes lipid peroxidation,which causes damage to myocytes,promoting myocardial damage.Furthermore,oxidative stress induces the binding of NML to its receptor RAGE,which in turn activates the nuclear factor-kB,and consequently,inflammatory cytokines.These inflammatory cytokines induce endothelial dysfunction,with increased expression of adhesion molecules,changes in endothelial permeability and changes in the expression of nitric oxide.In this sense,the therapeutic use of monoclonal antibodies(inflammatory reducers such as statins and sodium-glucose transport inhibitors)has demonstrated positive results in the regression of atherogenic plaques and consequently CAD.On the other hand,many studies have demonstrated a relationship between mitochondrial dynamics,diabetes,and cardiovascular diseases.This link occurs since ROS have their origin in the imbalance in glucose metabolism that occurs in the mitochondrial matrix,and this imbalance can have its origin in inadequate diet as well as some pathologies.Photobiomodulation(PBM)has recently been considered a possible therapeutic agent for cardiovascular diseases due to its effects on mitochondrial dynamics and oxidative stress.In this sense,therapies such as PBM that act on pro-inflammatory mediators and mitochondrial modulation could benefit those with cardiovascular diseases.

Coronary Artery Patterns in Diabetic Patients Undergoing Diagnostic Coronary Angiography-Data from a Major Cardiac Center in Yemen

Background: Diabetes mellitus (DM) is independently associated with an increased risk of cardiovascular mortality and morbidity, including coronary artery disease (CAD). CAD is a shared burden disease and the leading cause of death in developed and developing countries. We aimed to assess the angiographic patterns of coronary arteries in patients with DM in a developing country (Yemen) as the first study. Methods: This study is a cross-sectional, prospective, observational study that includes a total of 250 patients who were admitted for elective diagnostic coronary angiography. Results: 96 (38.4%) patients were diabetics;68% were male;mean age was 57 ± 11 years. The incidence of three-vessel disease was 31.2% of patients. Considering the severity of lumen occlusion, (11.2%) of patients had non-significant lesions, (37.6%) of patients had significant lesions, and (32%) had total occlusive lesions. Lesions were of LAD in 76%, RCA in 60%, and LCX in 52% of the population. Among diabetics, two and 3-vessel diseases (33.3% vs. 20.8% & 50% vs. 19.5%, P = 0.001), left main lesion (10.4% vs. 2.6%, P = 0.012), significant stenosis (41.7% vs. 35.1%, P = 0.032), total occlusion of coronary arteries (43.8% vs. 19.5%, P = 0.032) and type C lesion (66.7% vs. 35.1%, P = 0.010) were more frequent than non-DM patients. Conclusion: The burden of significant and severe coronary lesions is more common among DM, which may be the major cause of morbidity and mortality of DM in developing countries.