Diabetes Coronary Artery Disease Research Articles

Post-Load Insulin Secretion Patterns are Associated with Glycemic Status and Diabetic Complications in Patients with Type 2 Diabetes Mellitus.

To examine whether the different patterns of post-load insulin secretion can identify the heterogeneity of type 2 diabetes mellitus (T2DM). Six hundred twenty-five inpatients with T2DM at Jining No. 1 People's Hospital were recruited from January 2019 to October 2021. The 140 g steamed bread meal test (SBMT) was conducted on patients with T2DM, and glucose, insulin, and C-peptide levels were recorded at 0, 60, 120, and 180 min. To avoid the effect of exogenous insulin, patients were categorized into three different classes by latent class trajectory analysis based on the post-load secretion patterns of C-peptide. The difference in short- and long-term glycemic status and prevalence of complications distributed among the three classes were compared by multiple linear regression and multiple logistic regression, respectively. There were significant differences in long-term glycemic status (e. g., HbA1c) and short-term glycemic status (e. g., mean blood glucose, time in range) among the three classes. The difference in short-term glycemic status was similar in terms of the whole day, daytime, and nighttime. The prevalence of severe diabetic retinopathy and atherosclerosis showed a decreasing trend among the three classes. The post-load insulin secretion patterns could well identify the heterogeneity of patients with T2DM in short- and long-term glycemic status and prevalence of complications, providing recommendations for the timely adjustment in treatment regimes of patients with T2DM and promotion of personalized treatment.

Apolipoprotein A-IV of diabetic-foot patients upregulates tumor necrosis factor α expression in microfluidic arterial models.

Diabetic peripheral arterial atherosclerosis is one of the important characteristics of diabetic foot syndrome. Apolipoprotein (Apo A-IV) participates in various physiological processes, and animal studies have shown that it has roles of anti-atherosclerosis, prevention of platelet aggregation and thrombosis. Apo A-IV glycosylation is closely related to the occurrence and development of diabetic peripheral atherosclerosis. This study aimed to explore the mechanism of diabetic peripheral arterial lesions caused by glycosylated Apo A-IV. Type 2 diabetes mellitus (T2DM) and T2DM with diabetic foot patients (T2DM-F; n = 45, 30) were enrolled in this study, and individuals without diabetes (n = 35) served as normal controls (NC). In T2DM group, serum Apo A-IV content was higher than those in NC and T2DM-F group, as carboxymethyl lysine (CML) glycosylation of Apo A-IV in mixed serum from T2DM-F group was identified to be more significant than those in two other groups. Within a microfluidic arterial chip model, Apo A-IV from T2DM and T2DM-F group significantly increased transcription and protein levels of tumor necrosis factor alpha (TNF-α) in chip arteries, and CML expression was observed in T2DM-F group, which were associated with increased nuclear receptor subfamily 4 group A member 3 (NR4A3) expression. Recombinant human Apo A-IV could reverse the stimulating effect of serum Apo A-IV from T2DM-F group on TNF-α expression, and NR4A3 blocking peptide downregulated TNF-α expression by inhibiting NR4A3 expression. In the chip arteries, Apo A-IV from T2DM and T2DM-F increased TNF-α expression and turn them into a pre-atherosclerotic state, which might be one of the important mechanisms of glycosylated Apo A-IV to induce diabetic peripheral arterial lesions and eventually lead to diabetic foot.

Double Regulation of Supplement-Detoxification on Diabetic Atherosclerosis by Inhibiting Excessive Autophagy

<i>Objecive</i> To explore the mechanism of Huoxue Jiedu Jiangtang recipe (HJJR) in regulating the hyperactivation of endoplasmic reticulum stress (ERS) autophagy PERK-eIF2a-LC3 pathway, and reveal its prevention for diabetic atherosclerosis. <i>Methods</i> First, the rats were injected with streptozotocin intraperitoneally to make the diabetic models, and then the aortic balloon injury combined with high-fat feeding were used to make the models of atherosclerosis who were randomly divided into model group, western medicine group (Gliquidone + Benazepril), low-dose HJJR group (HJJR₁), high-dose HJJR group (HJJR₂), and accepted corresponding drugs for 8 weeks respectively. Another blank group was used as control. The changes of serum glycosylated hemoglobin (GHb), homocysteine (Hcy) and angiotensinII (Ang1I) were compared. HE staining was used to detect aortic pathology. The mRNA transcription of PRK-like endoplasmic reticulum kinase (PERK), eucaryotic translation initation factor 2α (eIF2α) and CCAAT / Enhance-Binding Protein Homologous Protein (CHOP) were tested by reverse- transcription polymerase chain reaction (RT-PCR). Western blot were used to detect the expression of autophagy activating protein ATG6 (Beclin-1), autophagy protein microtubule-associated protein light chain LC3-1, LC3-II and LC3-II/LC3-I. <i>Results </i>Compared with the model group, after the drug intervention, the aortic tissue injury in each drug group were reduced, and the improvement in the Chinese medicine group was significantly better than that of the western medicine group (P < 0.05). All treatment groups could significantly lowed the levels of serum GHb, Hcy, and Ang1I (P < 0.05), could down regulate the transcription level of PERK, eIF2α and CHOP mRNA (P < 0.05); and decreased the amount of Beclin 1, LC3-II and LC3-II/LC3-1 autophagy protein in aortic cells (P < 0.05). The effect of HJJF group was better, and it was more significant with the increase of HJJF dose. <i>Conclusion</i> HJJR can protect arteries by inhibiting ERS caused by metabolic disorder in diabetes, correcting the homeostasis affecting ER, reducing the overreaction of PERK-eIF2-LC3, and alleviating autophagy effect.

Sarcopenic obesity in comorbid patients

Sarcopenia is a multifactorial syndrome with an insufficiently studied pathogenesis, manifested by a generalized loss of muscle mass and skeletal muscle strength. Despite the fact that sarcopenia is a risk factor for mortality and disability, especially in the elderly, this pathology is rarely diagnosed. The lack of the uniform criteria for the diagnosis and comorbidity of the elderly patients create difficulties in the differential diagnosis of this condition. Sarcopenia is most often combined with endocrine pathologies, such as obesity and diabetes mellitus. An accelerated decrease in the muscle mass leads to a decrease in insulin sensitivity, resulting in insulin resistance, which, in turn, leads to the excessive accumulation of adipose tissue sarcopenic obesity. The results of the studies indicate a higher risk of metabolic syndrome, type 2 diabetes mellitus and atherosclerosis among individuals with sarcopenic obesity, as opposed to those with simple obesity or sarcopenia. A vicious circle consisting of age-related changes in the skeletal muscles, obesity and impaired glucose regulation leads to a more severe course of diseases and a negative impact on a person's life expectancy. Due to the fact that there are presently no clear criteria for the diagnosis of sarcopenic obesity, there are no unambiguous data on its prevalence. A search for the modern methods of research, prevention and treatment of this condition is required.

Disruption of COMMD1 accelerates diabetic atherosclerosis by promoting glycolysis.

Diabetes will lead to serious complications, of which atherosclerosis is the most dangerous. This study aimed to explore the mechanisms of diabetic atherosclerosis. ApoE-/- mice were fed with an high-fat diet diet and injected with streptozotocin to establish an in vivo diabetic atherosclerotic model. RAW 264.7 cells were treated with oxidized low-density lipoprotein particles (ox-LDL) and high glucose to produce an in vitro diabetic atherosclerotic model. In this study, we showed that diabetes promoted the progression of atherosclerosis in ApoE-/- mice and that high glucose potentiates macrophage proinflammatory activation and foam cell formation. Mechanistically, Copper metabolism MURR1 domain-containing 1(COMMD1) deficiency increased proinflammatory activation and foam cell formation, characterized by increased glycolysis, and then accelerated the process of atherosclerosis. Furthermore, 2-Deoxy-D-glucose (2-DG) reversed this effect. Taken together, we provided evidence that the lack of COMMD1 accelerates diabetic atherosclerosis via mediating the metabolic reprogramming of macrophages. Our study provides evidence of a protective role for COMMD1 and establishes COMMD1 as a potential therapeutic strategy in patients with diabetic atherosclerosis.

Tissue Factor and Vascular Endothelial Growth Factor in Detecting Thromboembolic Complications in Diabetic Atherosclerotic Patients.

Atherosclerosis, which is one of the leading causes of death all over the world, can create major or minor thromboembolic complications with the exponentially increasing diabetic status. Despite all the studies, the mechanism by which endothelial damage in atherosclerosis is triggered in diabetic setting is still not fully understood. In this study, tissue factor (TF), which is thought to act together in the formation of vasular endothelial growth factor (VEGF-A) and coagulopathy in diabetic atherosclerotic patients, may be an important indicator in this regard, a total of 100 cases who were undergone off-pump coronary artery bypass (OPCAB) which were at same risk group examined by dividing into diabetic status. Early postoperative process and biochemical parameters analyzed in terms of TF and VEGF-A levels measured before and after the operation. TF and VEGF-A expression of the T1DM group were statistically high compared to non-diabetics. Significantly longer hospital stays with changes in TF and VEGF-A were found in patients in the diabetic group compared to pre- and postoperatively, respectively; TF (95% CI: 0.879-0.992; p = 0.025), VEGF-A (95% CI: 0.964-0.991; p = 0.001) and hospital stay (95% CI: 1.96-7.49; p = 0.0001). Preoperatively measured carotid intima-media thickness (CT) was higher in diabetics and was significantly associated with atrial fibrillation (AF), (r = 0.873). Surgical team and protocols were same and OPCAB procedures were routinely applied to all patients in our clinic. No minor or major events were observed in any of the cases. TF and VEGF-A values in patients with diabetic atherosclerosis may be important in the early detection of thromboembolic complications.

L-limonene reduces aortic artery atherosclerosis by inhibiting oxidative stress/inflammatory responses in diabetic rats fed high-fat diet.

Atherosclerosis, a leading cause of mortality worldwide, is driven by multiple risk factors such as diabetes. Oxidative stress and inflammation assist interrelated roles in diabetes-accelerated atherosclerosis. Thereby, treatment of diabetic atherosclerosis from an oxidative stress/inflammatory perspective seems to be a more effective modality to prevent and delay plaque formation and progression. This study aimed to evaluate the effects of l-limonene (LMN) on oxidative stress/inflammatory responses in the aortic artery of diabetic atherosclerosis-modeled rats. Male Wistar rats (n = 30, 250-280 g, 12 weeks old) were used to establish a diabetic atherosclerosis model (8 weeks) using high-fat diet/low-dose streptozotocin. LMN (200 mg/kg/day) was administered orally, starting on day 30th before tissue sampling. Plasma lipid profiles, aortic histopathological changes, atherogenic index, aortic artery levels of oxidative stress markers (manganese superoxide dismutase, glutathione, and 8-isoprostane), inflammatory markers (tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10), and expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK, Sirtuin 1 (SIRT1), and p-p65/p65 proteins were evaluated. The administration of LMN to diabetic rats improved lipid profiles, aortic histopathological morphology, and atherogenic index (P < 0.05 to P < 0.001). It also increased enzymatic antioxidant activities, decreased 8-isoprostane level, suppressed inflammatory response, upregulated p-AMPK and SIRT1 proteins, and downregulated p-p65 protein (P < 0.05 to P < 0.01). Inhibiting the AMPK through the administration of compound C significantly abolished or reversed the positive effects of LMN in diabetic rats (P < 0.05 to P < 0.01). LMN treatment had dual anti-oxidative and anti-inflammatory actions against atherosclerosis in the aortic artery of diabetic rats. Atheroprotection by LMN was mediated partly through modulation of AMPK/SIRT1/p65 nuclear factor kappa B signaling pathway. LMN appears to be a promising anti-atherosclerotic modality to improve the quality of life in diabetic patients.

ОПЫТ ПРИМЕНЕНИЯ ДОНОРСКИХ СОСУДИСТЫХ ГРАФТОВ В ХИРУРГИИ МАГИСТРАЛЬНЫХ АРТЕРИЙ НИЖНИХ КОНЕЧНОСТЕЙ

Today, in surgery of the arteries of the lower extremities in diabetes mellitus and atherosclerosis, the autovein is the gold standard. It does not require any selection, conservation, or other preparation methods necessary for its application. However, its use in some cases is limited due to their parametric characteristics (length, diameter), loss of time for their preparation, and their absence. For these categories of patients, the method of choice is the use of vascular allografts. The article presents the experience of 25 cases of post-mortem donor vascular grafts in 24 patients with lower limb revascularization with critical ischemia. All patients were divided into 2 groups: 13 patients were included in the first group with neuroischemic form of diabetic foot syndrome, and 11 patients were included in the second group with obliterating atherosclerosis of vessels (arteries) of the lower extremities. Positive results were noted in 20 patients (83.3%). In the immediate and long-term periods after revascularization with a donor graft (1 - artery, 3 - vein), high amputations were performed in 4 (16.7%) cases, all patients with diabetes mellitus.

Association of interleukin 6 and uric acid levels in patients with type 2 diabetes mellitus.

Type 2 Diabetes Mellitus (T2DM) patients with coronary artery disease (CAD) coupled with hypertension (HTN) are leading cause of morbidity and mortality. Association of Interleukin 6 and uric acid levels can be used for early detection of CAD in patients with T2DM. This cross sectional study included 120 study participants, were sub grouped into three Group 1: controls (n=30), Group 2: CAD, HTN without T2DM (n=30) and Group 3: CAD, HTN with T2DM (n=30). Basic biochemical, clinical and experimental parameters were analysed and recorded for all the study subjects. The statistical analysis was done by using the SPSS 20.0. Individuals with CAD, HTN with T2DM had higher BMI, weight, SBP, and DBP levels than patients CAD, HTN without diabetes and controls. In CAD, HTN with T2DM study participants has been found to have higher serum levels of inflammatory cytokines like IL-6 and uric acids when compared to CAD, HTN without T2DM and controls. IL6 was significantly positive association with uric acid and negative association with age and HDL. These findings demonstrated a statistically significant positive connection between IL-6, and uric acid concentrations. The identified elevated levels of inflammatory cytokines and uric acids in type 2 diabetic and hypertensive CAD patients may aid in the identification of patients at higher risk.

MicroRNAs as Biomarkers for Coronary Artery Disease Related to Type 2 Diabetes Mellitus—From Pathogenesis to Potential Clinical Application

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD.

Efficacy, safety and therapeutic mechanism of Shen-Qi Xiao-Tan formula in the treatment of peripheral atherosclerosis in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial protocol

BackgroundPeripheral atherosclerosis is a common macrovascular complication of diabetes, but the treatment is limited. Chinese herbal medicine is the complementary and alternative therapy to delay the progression of atherosclerosis and reduce blood glucose and lipids. Shen-Qi Xiao-Tan (SQXT) formula is one of the prescriptions commonly used to treat diabetic peripheral atherosclerosis, but there is still a lack of high-quality evidence-based evidence.MethodsThis is a randomized, double-blind, placebo-controlled add-on trial that is expected to enroll 114 diabetic patients with peripheral atherosclerosis. After a 2-week run-in period, participants will been randomly assigned in a 1:1 ratio and receive 12 weeks of usual treatment and SQXT formula (treatment group) or usual treatment and placebo (control group). The primary outcome is the change in carotid intima-media thickness from baseline to endpoint. The secondary outcomes are the structure and function of peripheral arteries, blood glucose and lipids, traditional Chinese medicine syndrome score, and quality of life, and safety and endpoint events are evaluated. To explore the therapeutic mechanism through oxidative stress, inflammation, and advanced glycation end products, and lipidomics will be used to screen for biomarkers for diagnosis and efficacy evaluation.DiscussionThe objective of this trial is to evaluate the efficacy, safety and therapeutic mechanism of SQXT formula in the treatment of diabetic peripheral atherosclerosis. It will obtain high-quality evidence-based evidence and promote the treatment of diabetic macroangiopathy and the research and development of new drugs.Trial registrationThis trial is registered on Chinese Clinical Trials.gov with number ChiCTR2100047189 on 10 Jun 2021, and has been approved by the Ethical Review Committee of Hospital of Chengdu University of Traditional Chinese Medicine with number 2020KL-080.

Burden of Cardiovascular Disease in South Asians: Risk Factors Prevention and Early Screening is the Key

Cardiovascular diseases (CVD) have declined over the past two decades.1 However, despite improvements in population health, marked racial and ethnic disparities in longevity and CVD management persist. South Asians (SAs), people with ancestors from the Indian subcontinent constitute 1/5 of the world's population. During the late 1980s, the term “double burden of disease” was first used and can be defined as the burden of non-communicable diseases on top of infectious diseases that remain undefeated.2 Coronary artery disease (CAD), also called heart disease, stood out as the most common cause of this increasing double burden of diseases. The first study that was published related to South Asians and CAD risk was in 1991 by McKeigue et al.3 The study assessed the relation of central obesity and insulin resistance with high type 2 diabetes mellitus prevalence and CAD risk in immigrant SAs. A sample of industrial workers and general practitioners in the United Kingdom were shown to have a higher prevalence of diabetes, higher blood pressure, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride (TG), and lower high-density lipoprotein (HDL). This study confirms the existence of an insulin resistance syndrome in SAs.

Atherosclerosis in Diabetes: Celiac Disease as a Cherry on the Cake

IntroductionFew study has been conducted to unmask the potential role of celiac disease (CD) as a supplementary cardio-vascular risk factor in diabetes mellitus (DM) patients developing atherosclerosis. We conducted a systematic review to explore this peculiar association and discussed the related investigational studies. Material and MethodsWe carried out a systematic search on PubMed* via the query: (((“Atherosclerosis”[Mesh]) AND “Celiac Disease”[Mesh]) AND “Diabetes Mellitus”[Mesh]) AND (atherosclerosis[Title/Abstract] AND (celiac disease[Title/Abstract] OR coeliac disease[Title/Abstract]) AND (diabetes[Title/Abstract])) ResultsWe retrieved only 4 investigational studies: - carotid intima-media thickness (c-IMT) was significantly greater in patients with DM+CD than in patients with DM or CD (P<0.001) (Atherosclerosis, 2011) - Patients with DM+CD had lower HDL levels than patients with DM only (P = 0.017), i.e had a more atherogenic lipid profile (J Pediatr Endocrinol Metab, 2014) - In a Polish study, coexistence of CD with DM was not associated with a greater value of cIMT (Pediatr Endocrinol Diabetes Metab, 2016) - Mean value of atherosclerosis index in DM + CD was higher than in DM (P < 0.05) (Clin Biochem, 2018) ConclusionCeliac disease is a potential risk factor for developing athersclerosis in diabetic patients More studies with large series are needed to clarify this link and guide screening and management in clinical practice.

Frequency of Triple Vessel Coronary Artery Disease in Diabetic and Non Diabetic Patients Presenting with NSTEMI

Multi-vessel coronary artery disease (MVD) has profound challenges to the revascularization system. Several investigations showed diverse forms of CAD associated with complete or incomplete revascularization in MVD in PCI. Diabetic patient had more multi-vessel CAD as compared to non-diabetics. Objectives: To determine the frequency of triple vessel coronary artery disease and afterwards compare the triple vessel coronary artery disease in diabetic v/s non-diabetics in patients presenting with NSTEMI. Methods: This Descriptive Cross-Sectional Study was conducted at Emergency Department of the National Institute of Cardiovascular Diseases (NICVD), Karachi for Six months from March 4, 2019, to September 3, 2019. Samples size n=250 was calculated through non-probability consecutive sampling technique. All the patients of either gender presenting NSTEMI and undergone coronary angiography, aged &gt;40 and &lt; 75 years and agreed to participate after their volunteer affirmation were included in this study. Results: Out of 250 patients, 75.6% were male while 24.4% were female with a mean age of 56.60. Triple Vessel Disease was documented in 107(42.8%) patients. As for the study main objective variable diabetes, the comparative analysis of triple vessel disease between diabetic versus non-diabetic resulted in significant difference was noted i.e., p-value =0.030. Conclusions: Diabetic Mellitus has a significant factor for 3VD among the patients of NSTEMI patients. As a risk factor and comorbid, DM screening is a necessary factor in all NSTEMI patients who diagnosed with 3VD.

Analysis of Dynamic Association Between Diabetes Mellitus and Cardiovascular Disease

Diabetes mellitus (DM) is becoming more common because of the modern lifestyle. The two primary causes of mortality and disability among people are “diabetes mellitus (DM)” and “cardiovascular disease (CVD)”, which are linked closely. Diabetes mellitus is on the increase, it is quickly becoming one of the world’s most devastating and costly chronic diseases. Heart disease is the leading cause of mortality in diabetes and it has shown to have a significantly association with diabetes. Diabetic patients are more likely to have cardiovascular events due to the prevalence of CV diseases such as obesity, hypertension, and dyslipidemia. In addition, this study discusses the debated benefits of monitoring for subclinical atherosclerosis in asymptomatic individuals. Investigate on the connection between suboptimal glycemic management, and insulin resistance indicators, as possible variables connecting diabetes and cardiovascular disease is also done in this study. With this study it was reported that there is very little information is present on the early medication for treatment of the subclinical atherosclerosis in diabetics who are asymptomatic. The present study concluded that there is an urgent need for advanced research strategies to reduce the weight loss and overcome the obesity to reduce the prevalence of cardiovascular diseases.

Utility of screening for silent myocardial ischaemia in diabetes with an annual electrocardiogram.

Asymptomatic coronary artery disease (CAD) is common in people with diabetes mellitus, but there is a lack of consensus regarding appropriate screening for the condition. We performed a 12-lead electrocardiogram (ECG) on 312 consecutive participants with diabetes mellitus attending for routine annual outpatient review in order to determine the effectiveness of a yearly ECG in screening people with diabetes for asymptomatic CAD. Three of 312 participants (0.96%, 95% CI 0.2%-2.78%) had a newly identified ECG abnormality. One person had newly discovered atrial fibrillation. Two people had abnormalities which prompted further investigation for asymptomatic CAD. One of these participants underwent percutaneous coronary intervention. Seventeen further participants had abnormalities on ECG which had been previously documented, the majority having been present since their diagnosis of diabetes. A low positive yield of routine annual ECG in our study does not support its use as a screening tool for asymptomatic CAD in diabetes. Our findings support advice to perform an ECG at diagnosis of diabetes and to repeat only if a person develops relevant symptoms.

Salvianolic acid A regulates pyroptosis of endothelial cells via directly targeting PKM2 and ameliorates diabetic atherosclerosis.

Rescuing endothelial cells from pyroptotic cell death emerges as a potential therapeutic strategy to combat diabetic atherosclerosis. Salvianolic acid A (SAA) is a major water-soluble phenolic acid in the Salvia miltiorrhiza Bunge, which has been used in traditional Chinese medicine (TCM) and health food products for a long time. This study investigated whether SAA-regulated pyruvate kinase M2 (PKM2) functions to protect endothelial cells. In streptozotocin (STZ)-induced diabetic ApoE-/- mice subjected to a Western diet, SAA attenuated atherosclerotic plaque formation and inhibited pathological changes in the aorta. In addition, SAA significantly prevented NLRP3 inflammasome activation and pyroptosis of endothelial cells in the diabetic atherosclerotic aortic sinus or those exposed to high glucose. Mechanistically, PKM2 was verified to be the main target of SAA. We further revealed that SAA directly interacts with PKM2 at its activator pocket, inhibits phosphorylation of Y105, and hinders the nuclear translocation of PKM2. Also, SAA consistently decreased high glucose-induced overproduction of lactate and partially lactate-dependent phosphorylation of PKR (a regulator of the NLRP3 inflammasome). Further assay on Phenylalanine (PKM2 activity inhibitor) proved that SAA exhibits the function in high glucose-induced pyroptosis of endothelial cells dependently on PKM2 regulation. Furthermore, an assay on c16 (inhibitor of PKR activity) with co-phenylalanine demonstrated that the regulation of the phosphorylated PKR partially drives PKM2-dependent SAA modulation of cell pyroptosis. Therefore, this article reports on the novel function of SAA in the pyroptosis of endothelial cells and diabetic atherosclerosis, which provides important insights into immunometabolism reprogramming that is important for diabetic cardiovascular disease complications therapy.

Current Developments on Chemical Compositions, Biosynthesis, Color Properties and Health Benefits of Black Goji Anthocyanins: An Updated Review

Lycium ruthenicum is a therapeutic plant and its fruits (black goji) are commonly used as a traditional Chinese medicine. This review comprehensively discusses the recent research developments of black goji anthocyanins (BGAs), including chemical compositions, biosynthesis, color properties and health benefits. Among the 39 identified BGAs, most are 3,5-diglycoside derivatives of petunidin (&gt;95%) with an individual anthocyanin [petunidin 3-O-rutinoside (trans-p-coumaroyl)-5-O-glucoside], accounting for 80% of the total BGAs. Due to their unique anthocyanin profile, BGAs possess various health benefits, including antioxidant activities, α-glucosidase inhibiting activity, alleviating insulin resistance, improving mitochondrial function, anti-inflammatory effects, etc., and therefore have the potential to treat a range of chronic diseases, such as type 2 diabetes mellitus, memory disorders, stroke, colitis, atherosclerosis, cardiovascular and cerebrovascular diseases. In addition, BGAs exhibit a pH-dependent “red-purple-blue” pattern of color change and thus could be used as natural colorants and to prepare smart food packaging materials. This review is valuable for broad applications of BGAs as promising natural colorants, functional foods and potential herbal medicines.

External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry

AimsTHEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. Methods and resultsThe THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a ‘THEMIS-eligible population’ of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. ConclusionsIn a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be ‘THEMIS eligible.’ Clinical trial registrationhttp://www.clinicaltrials.gov identifier: NCT01991795

Oxidative stress and metabolic diseases: Relevance and therapeutic strategies.

Metabolic syndrome (MS) is a prominent cause of death worldwide, posing a threat to the global economy and public health. A mechanism that causes the oxidation of low-density lipoproteins (LDL) is associated with metabolic abnormalities. Various processes are involved in oxidative stress (OS) of lipoprotein. Although the concept of the syndrome has been fiercely debated, this confluence of risk factors is associated with a higher chance of acquiring type 2 diabetes mellitus (T2DM) and atherosclerosis. Insulin resistance has been found to play a significant role in the progression of these metabolism-associated conditions. It causes lipid profile abnormalities, including greater sensitivity to lipid peroxidation, contributing to the increased prevalence of T2DM and atherosclerosis. This review aims to cover the most recent scientific developments in dietary OS, the consequence of metabolic disorders, and their most significant clinical manifestations (T2DM and atherosclerosis). It will also emphasize the effects of dietary approaches in alleviating OS in MS.