scholarly journals Protease-Activated Receptor-Mediated Platelet Aggregation In Patients With Type 2 Diabetes On Potent P2Y12 Inhibitors

Author(s):  
Benjamin Panzer ◽  
Patricia P Wadowski ◽  
Kurt Huber ◽  
Simon Panzer ◽  
Thomas Gremmel

Abstract Background: Dual antiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI) with stent implantation. The new, more potent adenosine diphosphate (ADP) P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to improve patients’ outcomes. Whether or not these drugs have equal efficacy in diabetic as in non-diabetic individuals is disputed. Furthermore, platelets can be activated by thrombin, which is, at least in part, independent of ADP-inducible activation. Protease-activated receptor (PAR)-1 and -4 are thrombin receptors on human platelets activated by the agonists SFLLRN and AYPGKF, respectively. In the current study, we sought to compare the in vitro efficacy of prasugrel (n=121) and ticagrelor (n=99) to inhibit PAR-mediated platelet activation in patients with type 2 diabetes (n=55).Materials and Methods: We compared P2Y12-, PAR-1- and PAR-4-mediated platelet aggregation as assessed by multiple electrode platelet aggregometry between prasugrel- and ticagrelor-treated patients without and with type 2 diabetes who underwent acute PCI. Results: There were no significant differences of on-treatment platelet aggregation in response to ADP, SFLLRN and AYPGKF between patients on prasugrel or on ticagrelor. Diabetic and non-diabetic patients responded equally. There was no significant correlation between either; ADP-, SFLLRN-, or AYPGKF-inducible platelet aggregation and levels of HbA1c or the body mass index. However, we observed patients with high residual platelet reactivity to SFLLRN and AYPGKF in all cohorts.Conclusion: Prasugrel and ticagrelor inhibit platelet aggregation in diabetic and non-diabetic patients to a similar extent.

2015 ◽  
Vol 114 (08) ◽  
pp. 289-296 ◽  
Author(s):  
Romain Colas ◽  
Catherine Calzada ◽  
Quang Huy Lê ◽  
Nathalie Feugier ◽  
Christine Cugnet ◽  
...  

SummaryPlatelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.


2011 ◽  
Vol 6 (4) ◽  
pp. 381-390 ◽  
Author(s):  
Abhaykumar . ◽  
K. Nirmala ◽  
M.P.R. Prasad ◽  
Virendra V. Panpatil ◽  
T. Prasanna Krishna ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Francis Agyemang-Yeboah ◽  
Benjamin Ackon Jnr. Eghan ◽  
Max Efui Annani-Akollor ◽  
Eliezer Togbe ◽  
Sampson Donkor ◽  
...  

Background. Metabolic syndrome (MS) is a collection of cardiovascular risk factors comprising insulin resistance, dyslipidemia, obesity, and hypertension, which may cause further complications in diabetes. Although metabolic syndrome (MS) is increasing in incidence in diabetics and leading to significant cardiovascular diseases and mortality, there is dearth of data in Ghana. This study investigated metabolic syndrome, its prevalence, and its associated risk factors in type 2 diabetes at the Komfo Anokye Teaching Hospital, Kumasi, Ghana. Methods. The study involved 405 diabetic patients attending the Diabetic Clinic of the Komfo Anokye Teaching Hospital (KATH) Kumasi, in the Ashanti Region of Ghana. A well-structured questionnaire was used to obtain demographic background such as their age and gender. Anthropometric measurements were obtained using the Body Composition Monitor (Omron ® 500, Germany) which generated digital results on a screen and also by manual methods. Fasting venous blood was collected for the measurement of biochemical parameters comprising fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-c), and triglyceride (TG). Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Results. Out of the total of 405 participants, 81 were males and 324 were females, and the estimated mean age was 58.5 ± 9.9 years. The female patients exhibited higher mean waist circumference (WC) and mean hip circumference (HC) as well as an approximately higher body mass index than males (28.3 ± 5.1, 26.5 ± 4.2 for the female and male respectively). Overall, the prevalence of metabolic syndrome observed among the study population was 90.6%. Conclusions. The prevalence of metabolic syndrome observed among the study population was 90.6%, with a higher percentage in females than males. High triglyceride levels and high waist circumference were the main risk factors for MS in the diabetic population.


2021 ◽  
Vol 17 (4) ◽  
pp. 322-328
Author(s):  
A.V. Кovalchuk ◽  
О.В. Zinych ◽  
V.V. Korpachev ◽  
N.M. Кushnareva ◽  
О.В. Prybyla ◽  
...  

Recent studies have demonstrated the importance of bone as an endocrine organ that produces biologically active substances, which regulate both local bone metabolism and metabolic functions throughout the body. In the process of bone remodeling (formation/destruction), the active cells secrete specific biomarkers that help detect osteometabolic dysfunction. Among bone hormones, osteocalcin plays an important role as a coordinator of bone modeling processes, energy homeostasis, metabolism of glucose, lipids and minerals. Osteocalcin is a structural protein of the bone matrix, which is synthesized by osteoblasts and enters the bloodstream in the process of bone resorption. The level of osteocalcin in the serum is used as a specific marker of bone formation. Osteocalcin promotes pancreatic β-cell proliferation and insulin secretion, and also affects the insulin sensitivity of peripheral tissues. The inverse association of glycemia with the level of osteocalcin was revealed. Patients with type 2 diabetes mellitus usually have normal or even slightly elevated bone mineral density compared to age-appropriate controls. Decreased bone quality and increased risk of fractures are associated with changes in bone microarchitecture and local humoral environment. An imbalance in osteoblast/osteoclast activity may be due to oxidative stress and the accumulation of glycosylation end products, which contributes to chronic inflammation and bone resorbtion in patients with diabetes. It is shown that the level of osteocalcin in the blood serum is significantly reduced compared to healthy controls, both in patients with type 1 diabetes mellitus and, especially, in type 2 diabetes mellitus. Given the importance of developing new approaches to the diagnosis and correction of metabolic disorders in diabetic patients, the study of the influence of bone hormones on hormonal and metabolic parameters and bone status, including the risk of fractures, remains relevant in modern diabetology.


Author(s):  
Robson Bonoto Teixeira ◽  
Luciana Moreira Lima ◽  
Yuri Lucas Xavier ◽  
Carlos Gabriel de Lade ◽  
Gabriela Fernandes Lopes ◽  
...  

Introduction: Type 2 Diabetes Mellitus affects current society, and is associated with overweight and obesity. Physical exercise has been showing favorable results in the anthropometric parameters and in the gain of joint flexibility and body mobility in these individuals. Objective: The objective of this study was to analyze the interference of an exercise program in anthropometric measures, flexibility and body mobility in type 2 diabetics. Method: This is a longitudinal study, performed with 14 type 2 diabetic patients, with a mean age of 55± 9 years, both genders, separated in aerobic group (n=8) and resistance group (n=6). The body mass index, waist circumference, abdominal circumference, hip circumference, waist-hip ratio, fat percentage, limp-femoral flexibility and body mobility were assessed before and after a 10-week period of aerobic or resistance exercises with a weekly frequency of 3 days. Results: For the analysis of the results, it was applied the paired t test (pre x post exercise) and independent t test (aerobic group x resistance group) with significance level of 5%. No significant differences were found in the anthropometric variables in both groups after the 10-week period of supervised training. In relation to the body mobility test, we observed a significant difference in the total sample (p=0.02), in the aerobic group (p=0.02) and in the resistance group (p=0.04). The coxofemoral flexibility test showed significant improvement (p=0.02) in the total sample and clinical improvement in aerobic (p=0.12) and resistance (p=0.09) groups. Conclusion: Both aerobic and resistance training provided positive effects in the coxofemoral flexibility and body mobility tests. In contrast, there was no significant improvement in anthropometric variables after 10 weeks of physical exercise.


2020 ◽  
Vol 4 (6) ◽  
pp. 340-346
Author(s):  
A.B. Fursov ◽  
◽  
R.A. Fursov ◽  
O.B. Ospanov ◽  
◽  
...  

A large number of patients with type 2 diabetes (T2D) have a high incidence of complications and disease decompensation, which becomes the reason for therapy inefficacy. In recent years, endocrinologists and diabetologists are increasingly paying attention to surgical methods for treating T2D. The review attempts to study and systematize new trends in the treatment of T2D, as well as to determine the historical vector of changes in diabetologist views on the control, stabilization of the glycemic level in diabetic patients, and surgical methods.A retrospective study of scientific approaches to the treatment of diabetes confirmed the opinion of some researchers that the evolution of treatment methods commonly consisted of improving control and means of insulin delivery to the body. The analysis of scientific papers that confirm that detection of glycemic disorders among those admitted to the surgical hospital has a direct and immediate benefit both in a planned and urgent order. The growth of economic costs associated with insufficient glycemic control in diabetic patients was studied. Over the past decades, medical care standards for diabetes are analyzed in chronological order. Using the American Diabetes Association Guidelines, new trends in the treatment of T2D have been developed, and a stable vector in changing views on the efficacy of surgical bariatric and metabolic methods has been identified.KEYWORDS: medical care standards, type 2 diabetes, glycemia, evolution of diabetes mellitus treatment, economic costs, guidelines, metabolic surgery, endoscopic methods.FOR CITATION: Fursov A.B., Fursov R.A., Ospanov O.B. Medical care standards for diabetes in the hospital: evolution of views from glycemic control to metabolic surgery. Russian Medical Inquiry. 2020;4(6):340–346. DOI: 10.32364/2587-6821-2020-4-6-340-346.


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Nathanne S Ferreira ◽  
Thiago Bruder-Nascimento ◽  
Camila A Pereira ◽  
Camila Z Zanotto ◽  
Douglas S Prado ◽  
...  

Diabetic patients and animal models of type 2 diabetes (DM2) display increased plasma aldosterone (aldo) levels. Aldo induces vascular inflammation and endothelial dysfunction. NOD-like receptors, which are pattern recognition receptors involved in a variety of host innate immune responses, promote vascular inflammation. We hypothesized that aldo via mineralocorticoid receptors (MR) activates the inflammasome platform in the vasculature of DM2 mice. Control (db/+) and diabetic (db/db) mice were treated with vehicle or spironolactone (spiro - MR antagonist, 50 mg/Kg/day). Mesenteric resistance arteries (MA) from db/db mice exhibited reduced acetylcholine (ACh) dilation, which was reversed by spiro [Emax (% of relaxation): db/+: 78.5±4.1; db/db: 40.5±6.4; db/+spiro: 77.0±3.8; db/db+spiro: 62.8±5.9 n=3-6 p<0.05]. Spiro treatment reduced caspase-1 and mature IL-1β content in MA from db/db mice. Spiro also reduced caspase-1 activity in macrophages from peritoneal lavage of db/db mice [% of activity: db/+: 33.9±2.5; db/db: 51.8±7.4; db/+spiro: 31.1±1.9; db/db+spiro: 34.8±3.8 n=4-7, p<0.05]. In vitro, aldo increased mature IL-1β in vascular smooth muscle cells (VSMC) (cont: 0.9±0.01 ; LPS+Nigericine: 6.1±2.1 ; Aldo 4h: 9.7±2.6; LPS+Aldo 4h: 12.8±1.9 n=3-5, p<0.05). To determine whether aldo in vivo directly activates NLRP3/inflammasome in the vasculature and whether NLRP3 activation contributes to aldo-induced vascular injury, aldo was infused (600 ug/Kg/day for 14 days) in wild type (WT) and NLRP3 knockout mice ( NLRP3-/- ) after bone marrow transplantation from WT donor. The groups were constituted: WT->WT, WT->WT+aldo and WT-> NLRP3 -/-+aldo. NLRP3 -/- mice were protected against aldo-induced endothelial dysfunction [Emax: WT: 89.3±2.9; WT+aldo: 39.8±1.8; NLRP3-/- +aldo: 87.7±4.2, p<0.05]. Aldo treatment leaded to endothelial dysfunction in WT ->WT mice, but WT-> NLRP3 -/- mice were protected from aldo-induced endothelial dysfunction [Emax: WT->WT: 95.1±3.1; WT->WT+aldo: 57.1±4.7; WT->NLRP3-/-+aldo: 85.3±3.1 p<0.05]. These results suggest that NLRP3/inflammasome in the vasculature plays a crucial role on aldo/MR-induced vascular damage and on DM2-associated vascular dysfunction. Financial Support: FAPESP, CAPES, CNPq.


2008 ◽  
Vol 77 (3) ◽  
pp. 1008-1014 ◽  
Author(s):  
Sunny Park ◽  
Jeremy Rich ◽  
Frank Hanses ◽  
Jean C. Lee

ABSTRACT Foot and ankle infections are the most common cause of hospitalization among diabetic patients, and Staphylococcus aureus is a major pathogen implicated in these infections. Patients with insulin-resistant (type 2) diabetes are more susceptible to bacterial infections than nondiabetic subjects, but the pathogenesis of these infections is poorly understood. C57BL/6J-Lepr db /Lepr db (hereafter, db/db) mice develop type 2 diabetes due to a recessive, autosomal mutation in the leptin receptor. We established a S. aureus hind paw infection in diabetic db/db and nondiabetic Lepr +/+ (+/+) mice to investigate host factors that predispose diabetic mice to infection. Nondiabetic +/+ mice resolved the S. aureus hind paw infection within 10 days, whereas db/db mice with persistent hyperglycemia developed a chronic infection associated with a high bacterial burden. Diabetic db/db mice showed a more robust neutrophil infiltration to the infection site and higher levels of chemokines in the infected tissue than +/+ mice. Blood from +/+ mice killed S. aureus in vitro, whereas db/db blood was defective in bacterial killing. Compared with peripheral blood neutrophils from +/+ mice, db/db neutrophils demonstrated a diminished respiratory burst when stimulated with S. aureus. However, bone marrow-derived neutrophils from +/+ and db/db mice showed comparable phagocytosis and bactericidal activity. Our results indicate that diabetic db/db mice are more susceptible to staphylococcal infection than their nondiabetic littermates and that persistent hyperglycemia modulates innate immunity in the diabetic host.


2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Gunilla T. Westermark ◽  
Per Westermark

Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.


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