The structural and functional changes of blood cells and molecular components in diabetes mellitus

Szablewski, Leszek; Sulima, Anna

doi:10.1515/hsz-2016-0196

Cited by 42 publications

(28 citation statements)

References 96 publications

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“…In this study, the presence of diabetes mellitus (DM) in the OA-treated subject population (7 out of the 25 subjects tested) was identified as a potential bias for the observed results, since DM is known to affect both leukocyte and platelet functions [ 76 , 77 ]. Indeed, chronic and acute hyperglycemia can trigger platelet activation [ 78 , 79 ], while, in diabetic patients, the production of several growth factors involved in initiating and sustaining the healing process are compromised [ 18 ]; for example, VEGF and TGF-beta protein expressions are reduced in diabetic dermal wounds [ 80 , 81 ].…”

Section: Discussionmentioning

confidence: 99%

Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes

et al. 2020

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Patients suffering from tissue ischemia, who would greatly benefit from angiogenesis-promoting therapies such as hypoxia preconditioned blood-derived secretomes commonly receive oral anticoagulation (OA) and/or have diabetes mellitus (DM). In this study, we investigated the effect of OA administration on the in vitro angiogenic potential of hypoxia preconditioned plasma (HPP) and serum (HPS), prepared from nondiabetic/diabetic subjects who did not receive OA (n = 5) or were treated with acetylsalicylic acid (ASA, n = 8), ASA + clopidogrel (n = 10), or nonvitamin K antagonist oral anticoagulants (n = 7) for longer than six months. The effect of DM was differentially assessed by comparing HPP/HPS obtained from nondiabetic (n = 8) and diabetic (n = 16) subjects who had not received OA in the past six months. The concentration of key proangiogenic (vascular endothelial growth factor or VEGF) and antiangiogenic (thrombospondin-1 or TSP-1 and platelet factor-4 or PF-4) protein factors in HPP/HPS was analyzed via ELISA, while their ability to induce microvessel formations was examined in endothelial cell cultures. We found that OA use significantly reduced VEGF levels in HPP, but not HPS, compared to non-OA controls. While HPP and HPS TSP-1 levels remained largely unchanged as a result of OA usage, HPS PF-4 levels were significantly reduced in samples obtained from OA-treated subjects. Neither OA administration nor DM appeared to significantly reduce the ability of HPP or HPS to induce microvessel formations in vitro. These findings indicate that OA administration does not limit the angiogenic potential of hypoxia preconditioned blood-derived secretomes, and therefore, it does not prohibit the application of these therapies for supporting tissue vascularization and wound healing in healthy or diabetic subjects.

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Section: Discussionmentioning

confidence: 99%

Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes

et al. 2020

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“…Erythrocytes of patients with T2D exhibit impaired deformability related to increased HbA 1c and accumulation of intracellular sorbitol or to the stiffness of red blood cell membranes probably due to oxidative modification of the proteins and to an imbalance of the cholesterol/phospholipids ratio [ 46 ]. Moreover, RBCs incubated in an elevated level of glucose showed a significantly increased protein glycation and induced ATPases activity [ 47 ] and were are highly susceptible to oxidative damage as a result of the high polyunsaturated fatty acid content of their membranes and the high cellular concentration of oxygen and hemoglobin [ 46 ]. Therefore, we hypothesize that these processes may impact the rheological properties of RBCs, cause membrane damage and potentially alter the RBCs contraction, influencing blood clot shrinkage properties.…”

Section: Discussionmentioning

confidence: 99%

Polyhedrocytes in blood clots of type 2 diabetic patients with high cardiovascular risk: association with glycemia, oxidative stress and platelet activation

Gajos

Siniarski

Natorska

et al. 2018

Cardiovasc Diabetol

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BackgroundLittle is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients.MethodsIn 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9–7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro.ResultsPolyhedrocytes content in contracted clots was positively correlated with glucose (r = 0.24, p = 0.028), glycated hemoglobin (r = 0.40, p = 0.024), total cholesterol (r = 0.22, p = 0.044), TBARS (r = 0.60, p = 0.0027), P-selectin (r = 0.54, p = 0.0078) and platelet factor-4, PF4 (r = 0.59, p = 0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥ 10th percentile) (n = 83, 85.6%) had higher glucose (+ 15.7%, p = 0.018), fibrinogen (+ 16.6%, p = 0.004), lower red blood cell distribution width (RDW, − 8.8%, p = 0.034), reduced plasma clot density (− 21.8% Ks, p = 0.011) and impaired fibrinolysis (+ 6.5% CLT, p = 0.037) when compared to patients with lesser amount of polyhedrocytes (< 10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r = 0.79, p = 0.036 and r = 0.67, p = 0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p = 0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR = 0.61, 95% CI 0.39–0.92).ConclusionsPoor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0789-6) contains supplementary material, which is available to authorized users.

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“…Il existe de nombreux mécanismes par lesquels l'hyperglycémie et la glycosurie pourraient altérer la sensibilité aux infections : les cellules immunitaires en général et les polynucléaires neutrophiles en particulier subissent d'impor tantes modifications au niveau fonctionnel et structurel chez les patients diabétiques 70,71 . L'oxygénation locale peut être altérée par la micro-angiopathie ainsi que les altérations rhéologiques (réduction de la déformabilité des érythrocytes, aggrégabilité accrue, surreprésentation des protéines de phase aigüe).…”

Section: Plausibilite Biologiqueunclassified

Association between diabetes mellitus and infection : which evidence for a causal role of hyperglycemia ?

Richard¹,

Buttafuoco²,

Vanhaeverbeek³

et al. 2018

Rev Med Brux

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RESUME L'association statistique entre le diabète et l'infection est en accord avec les observations de la pratique clinique quotidienne et les notions anciennes de la physiopathologie. Dans cet article, nous cherchons à déterminer si, dans cette association, l'hyperglycémie en elle-même constitue un facteur causal. Pour ce faire, nous avons vérifié si cette hypothèse est en accord avec les neuf critères de Bradford-Hill. Nous avons procédé en analysant systématiquement la littérature, en partant d'une liste de tableaux cliniques infectieux définis. Nous avons donc vérifié successivement la force de cette association, sa stabilité, sa spécificité, sa temporalité, l'existence d'un effet dose-réponse, sa plausibilité biologique, la cohérence de l'hypothèse, les données expérimentales et l'existence possible d'analogies. Nous avons ainsi pu identifier les tableaux cliniques concernés, ainsi que les risques relatifs et rapports de cote associés. Nous avons également relevé certaines affections hautement spécifiques du diabète, comme la pyélonéphrite emphysémateuse ou l'otite maligne externe. Nous avons pu voir que l'hypothèse testée s'insère correctement dans les données de la biologie et de l'épidémiologie moderne. Huit des neuf critères de Bradford-Hill étant remplis, il existe effectivement une association causale entre l'hyperglycémie, la glycosurie et l'augmentation du risque d'infection dans le diabète. Rev Med Brux 2018 ; 39 : 495-504 ABSTRACTThe statistical association between diabetes mellitus and infectious diseases is consistent with the observations of daily clinical practice and ancillary notions of pathophysiology. In this issue, we aim to establish whether hyperglycemia itself plays a causal role in this association. To do so, we have verified whether this hypothesis fulfilled the Bradford Hill criteria. We have systematically reviewed the medical literature from a panel of infectious diseases. We have successively verified the strength of the association, its stability, specificity, and temporality, the existence of a dose-response effect, its coherence, the experimental data and available analogy. We could identify the clinical affections of interest and related relative risks and odds ratios. We also have identified several affections highly specific of diabetic patients, such as emphysematous pyelonephritis and malignant external otitis. We could conclude that the the hyperglycemia and glycosuria play a causal role in the relation between diabetes mellitus and the risk of infectious disease. Rev Med Brux 2018 ; 39 : 495-504

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The structural and functional changes of blood cells and molecular components in diabetes mellitus

Cited by 42 publications

References 96 publications

Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes

Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes

Polyhedrocytes in blood clots of type 2 diabetic patients with high cardiovascular risk: association with glycemia, oxidative stress and platelet activation

Association between diabetes mellitus and infection : which evidence for a causal role of hyperglycemia ?

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