scholarly journals Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Agata Hanna Bryk-Wiązania ◽  
Anetta Undas
Keyword(s):  
Type 2 Diabetes ◽  
Posttranslational Modifications ◽  
Platelet Reactivity ◽  
Fibrin Clot ◽  
Typical Feature ◽  
Current Data ◽  
Complement C3 ◽  
Diabetic Patients ◽  
Clot Structure

AbstractA prothrombotic state is a typical feature of type 2 diabetes mellitus (T2DM). Apart from increased platelet reactivity, endothelial dysfunction, hyperfibrinogenemia, and hypofibrinolysis are observed in T2DM. A variety of poorly elucidated mechanisms behind impaired fibrinolysis in this disease have been reported, indicating complex associations between platelet activation, fibrin formation and clot structure, and fibrinolysis inhibitors, in particular, elevated plasminogen antigen inhibitor-1 levels which are closely associated with obesity. Abnormal fibrin clot structure is of paramount importance for relative resistance to plasmin-mediated lysis in T2DM. Enhanced thrombin generation, a proinflammatory state, increased release of neutrophil extracellular traps, elevated complement C3, along with posttranslational modifications of fibrinogen and plasminogen have been regarded to contribute to altered clot structure and impaired fibrinolysis in T2DM. Antidiabetic agents such as metformin and insulin, as well as antithrombotic agents, including anticoagulants, have been reported to improve fibrin properties and accelerate fibrinolysis in T2DM. Notably, recent evidence shows that hypofibrinolysis, assessed in plasma-based assays, has a predictive value in terms of cardiovascular events and cardiovascular mortality in T2DM patients. This review presents the current data on the mechanisms underlying arterial and venous thrombotic complications in T2DM patients, with an emphasis on hypofibrinolysis and its impact on clinical outcomes. We also discuss potential modulators of fibrinolysis in the search for optimal therapy in diabetic patients.

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

2021 ◽  
Author(s):  
Benjamin Panzer ◽  
Patricia P Wadowski ◽  
Kurt Huber ◽  
Simon Panzer ◽  
Thomas Gremmel
Keyword(s):  
Type 2 Diabetes ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
The Body ◽  
Diabetic Patients ◽  
P2y12 Inhibitors ◽  
Platelet Aggregometry

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.

Interplay between elevated cellular fibronectin and plasma fibrin clot properties in type 2 diabetes

2017 ◽  
Vol 117 (09) ◽  
pp. 1671-1678 ◽  
Author(s):  
Małgorzata Konieczyńska ◽  
Agata Bryk ◽  
Krzysztof Malinowski ◽  
Katarzyna Draga ◽  
Anetta Undas
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Vascular Injury ◽  
Microvascular Complications ◽  
Fibrin Clot ◽  
Diabetic Patients ◽  
Lysis Time ◽  
Supplementary Material ◽  
Cellular Fibronectin

SummaryType 2 diabetes is associated with faster formation of poorly lysable, denser fibrin clots and elevated cellular fibronectin (cFn), a marker of vascular injury. We investigated whether cFn affects clot properties in type 2 diabetes. In 200 consecutive patients with type 2 diabetes and 100 control subjects matched for age and sex, we determined plasma cFn along with clot formation and degradation using turbidimetric and permeability assays. Diabetic patients had elevated cFn (median, 3.99 [interquartile range, 2.87–4.81] µg/ml]), increased clot density (MaxAbsC) and prolonged lysis time (LysT) compared with those without type 2 diabetes (all p<0.01). Diabetic patients with documented cardiovascular disease (CVD, n=127, 63.5 %) had increased cFn (4.53 [3.68–4.95] µg/ml), decreased clot permeability (Ks) and increased MaxAbsC compared with those without CVD (all p<0.001). Diabetic patients with cFn in the top quartile (>4.81 µg/ml) were two times more likely to have CVD compared with those in the lowest quartile (odds ratio 1.80, 95 % confidence interval 1.41–2.46, p<0.001). No differences in cFn were observed in relation to microvascular complications. After adjustment for potential confounders, cFn accounted for 10.2 % of variance in Ks, 18.2 % of variance in clot density and 10.2 % of variance in AUC in diabetic patients. This study shows that elevated cFn is associated with unfavourably modified clot properties in type 2 diabetes, especially with concomitant CVD, which indicates novel links between vascular injury and prothrombotic alterations in diabetes. Coagulation, cellular fibronectin, type 2 diabetes, cardiovascular disease.Supplementary Material to this article is available online at www.thrombosis-online.com.

Thrombus and antiplatelet therapy in type 2 diabetes mellitus

2012 ◽  
Vol 108 (11) ◽  
pp. 937-945 ◽  
Author(s):  
Girish Viswanathan ◽  
Sally Marshall ◽  
Clyde Schechter ◽  
Karthik Balasubramaniam ◽  
José Badimon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Medical Therapy ◽  
Platelet Reactivity ◽  
Controlled Trial ◽  
Diabetic Patients ◽  
Coronary Syndrome ◽  
Stable Cad

SummaryType 2 diabetes mellitus (T2DM) is associated with higher rates of thrombotic complications in patients with coronary artery disease (CAD) despite optimal medical therapy. Thrombus area was measured in T2DM and non-diabetic patients receiving aspirin and clopidogrel 7–10 days after troponin positive Non ST-elevation acute coronary syndrome (NSTE-ACS). Secondly, we assessed response to clopidogrel in naive patients with T2DM and stable CAD in a randomised controlled trial. Thrombus area was measured by Badimon chamber and platelet reactivity by VerifyNow®. In T2DM patients presenting with NSTE-ACS, thrombus area was greater compared to non-diabetic patients (mean ± SD, 20,512 ± 12,567 [n=40] vs. 14,769 ± 8,531 [n=40] μm2/mm, p=0.02) Clopidogrel decreased thrombus area among stable CAD patients with T2DM (mean ± SD, Clopidogrel [n=45]: 13,978 ± 5,502 to 11,192 ± 3,764 μm2/mm vs. placebo [n=45]: 13,959 ± 7,038 to 14,201 ± 6,780 μm2/mm, p<0.001, delta values: clopidogrel vs. placebo, mean ± SD, 2,786 ± 4,561 vs. –249 ± 2,478, p<0.0005). Only 44% of patients with CAD and T2DM responded to clopidogrel as per VerifyNow® (cut-off PRUz value of ≥240). Importantly, no correlation was observed between thrombus area and VerifyNow® values (rho 0.08, p=0.49). Thrombus area values were similar among hypo-responders and good responders to clopidogrel (mean thrombus area ± SD: 12,186 ± 4,294 vs. 10,438 ± 3,401; p=0.17). Type 2 diabetes mellitus is associated with an increased blood thrombogenicity among NSTE-ACS patients on currently recommended medical therapy. Thrombus area was significantly reduced in all stable CAD patients independently of their response to clopidogrel therapy.

scholarly journals Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ceren Eyileten ◽  
Agnieszka Kaplon-Cieslicka ◽  
Dagmara Mirowska-Guzel ◽  
Lukasz Malek ◽  
Marek Postula
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Neurotrophic Factor ◽  
Platelet Reactivity ◽  
Brain Derived Neurotrophic Factor ◽  
Diabetic Patients ◽  
Antidiabetic Effect ◽  
Coronary Syndrome

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM). BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM.

scholarly journals Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients

2015 ◽  
Vol 114 (08) ◽  
pp. 289-296 ◽  
Author(s):  
Romain Colas ◽  
Catherine Calzada ◽  
Quang Huy Lê ◽  
Nathalie Feugier ◽  
Christine Cugnet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Platelet Aggregation ◽  
Docosahexaenoic Acid ◽  
Platelet Function ◽  
Plasma Lipids ◽  
Platelet Reactivity ◽  
Thromboxane B2 ◽  
Diabetic Patients

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.

Association of Major Dietary Patterns with General and Abdominal Obesity in Iranian Patients with Type 2 Diabetes Mellitus

2015 ◽  
Vol 85 (3-4) ◽  
pp. 145-155 ◽  
Author(s):  
Marjan Ghane Basiri ◽  
Gity Sotoudeh ◽  
Mahmood Djalali ◽  
Mohammad Reza Eshraghian ◽  
Neda Noorshahi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Abdominal Obesity ◽  
Dietary Patterns ◽  
Dietary Pattern ◽  
Diabetic Patients ◽  
General Obesity ◽  
Healthy Dietary Pattern

Abstract. Background: The aim of this study was to identify dietary patterns associated with general and abdominal obesity in type 2 diabetic patients. Methods: We included 728 patients (35 - 65 years) with type 2 diabetes mellitus in this cross-sectional study. The usual dietary intake of individuals over 1 year was collected using a validated semi-quantitative food frequency questionnaire. Weight, height, and waist circumference were measured according to standard protocol. Results: The two major dietary patterns identified by factor analysis were healthy and unhealthy dietary patterns. After adjustment for potential confounders, subjects in the highest quintile of the healthy dietary pattern scores had a lower odds ratio for the general obesity when compared to the lowest quintile (OR = 0.45, 95 % CI = 0.26 - 0.79, P for trend = 0.02), while patients in the highest quintile of the unhealthy dietary pattern scores had greater odds for the general obesity (OR = 3.2, 95 % CI = 1.8 - 5.9, P for trend < 0.001). There were no significant associations between major dietary patterns and abdominal obesity, even after adjusting for confounding factors. Conclusion: This study shows that in patients with type 2 diabetes mellitus, a healthy dietary pattern is inversely associated and an unhealthy dietary pattern is directly associated with general obesity.

ESTIMATION OF SERUM FERRITIN LEVELS IN TYPE 2 DIABETIC PATIENTS AND ITS RELATION WITH HbA1C LEVEL.

2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Shah Namrata Vinubhai ◽  
Pardeep Agarwal ◽  
Bushra Fiza ◽  
Ramkishan Jat
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Sugar ◽  
Serum Ferritin ◽  
Inflammatory Marker ◽  
Control Group ◽  
Diabetic Patients ◽  
Positive Correlation

Background: Serum ferritin is known as an index for body iron stores also as an inflammatory marker and it is influenced by several disease. We were looking for a correlation between HbA1c and S. Ferritin in type 2 DM. Methodology: The present study a total of 150 participants were enrolled of which 100 were confirmed cases of Type 2 Diabetes Mellitus and rest 50 age and sex matched healthy subjects constituted the control group. All were screened for HbA1c, Fasting blood sugar, Post prandial blood sugar and S.Ferritin. Results: A highly significant variation and positive correlation was observed with respect to S.Ferritin and HbA1c levels. Mean S.Ferritin was high in the subgroup with poor glycemic control. Conclusion: The fasting, post prandial sugar levels, HbA1c and S.Ferritin were significantly higher in the diabetic subjects. This study shows a positive correlation between HbA1c and S. Ferritin levels. So we can conclude that in diabetic patients S. Ferritin may serve as an independent marker of poor glycemic and metabolic control. Keywords: Serum ferritin, Type 2 Diabetes Mellitus, HbA1c.

Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update

2019 ◽  
Vol 25 (23) ◽  
pp. 2510-2525 ◽  
Author(s):  
Bashir Usman ◽  
Neha Sharma ◽  
Saurabh Satija ◽  
Meenu Mehta ◽  
Manish Vyas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Patient Compliance ◽  
Postprandial Hyperglycemia ◽  
Diabetic Patients ◽  
Poor Patient ◽  
Glucosidase Inhibitors ◽  
Poor Patient Compliance ◽  
Recent Developments ◽  
Alpha Glucosidase

The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety. Alphaglucosidase is a family of enzyme originated from the pancreas which plays a role in the anabolism of 80-90% of carbohydrate consumed into glucose. This glucose is absorbed into the blood and results in frank postprandial hyperglycemia and worsens the conditions of diabetic patients which precipitate complications. Inhibition of these enzymes helps to prevent postprandial hyperglycemia and the formation of glycated end products. Alphaglucosidase inhibitors are reported to be more important in adequate control of type 2, but marketed drugs have various side effects, such as poor patient compliance and also expensive. This proves the needs for other class of drugs with better efficacy, safety, patient compliance and economic. In this review, we have emphasized the recent advances in the field of new alpha-glucosidase inhibitors with improved safety and pharmacological profile.

Serum Complement C3 and Type 2 Diabetes in Rheumatoid Arthritis: A Case-Control Study

2018 ◽  
Vol 13 (3) ◽  
pp. 215-221 ◽  
Author(s):  
Francesco Ursini ◽  
Salvatore D`Angelo ◽  
Emilio Russo ◽  
Giorgio Ammerata ◽  
Ludovico Abenavoli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
Case Control Study ◽  
Case Control ◽  
Complement C3 ◽  
Serum Complement ◽  
Control Study

scholarly journals Functional Cereal Products in the Diet for Type 2 Diabetes Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Ada Krawęcka ◽  
Aldona Sobota ◽  
Emilia Sykut-Domańska
Keyword(s):  
Type 2 Diabetes ◽  
Nutritional Value ◽  
Glycaemic Index ◽  
Modern World ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Major Health ◽  
Cereal Products

Type 2 diabetes has become one of the major health problems of the modern world. It is assumed that environmental factors have a significant impact on the development of the disease, and great importance is ascribed to the diet, which can be modified accordingly. The diet can exert prophylactic and therapeutic effects; changes in the diet in advanced disease can improve the quality of life of diabetic patients and minimise the risk of complications, which are the direct cause of diabetes-related death. Functional food, which has a potentially health-enhancing effect in addition to its nutritional value, has been increasingly recognised and required. Cereal products are crucial in diabetic nutrition. Their function can additionally be enhanced by fortification with compounds with proven hypoglycaemic effects. Pasta has a low glycaemic index and is a good carrier of fortifying substances; hence, it can be highly recommended in diets for diabetic patients.

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