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Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

ABSTRACT: OJECTIVES:Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date. PATIENTS/METHODS:This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ?6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). RESULTS:Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04). CONCLUSIONS:Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.

SUBMITTER: Osinski M

PROVIDER: S-EPMC7544075 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

Osiński Maciej M Mantaj Urszula U Kędzia Małgorzata M Gutaj Paweł P Wender-Ożegowska Ewa E

PloS one 20201008 10

<h4>Ojectives</h4>Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date.<h4>Patients/methods</h4>This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into t ...[more]

PMID: 33031385

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Project description:The novel severe acute respiratory syndrome viral disease outbreak due to SARS-CoV-2 is a rapidly evolving disease and represents one of the greatest medical challenges in recent times. It is believed that SARS-CoV-2 has migrated from bats to an intermediate host and then to humans. This article aims at the mechanism and management of prothrombotic state in COVID-19 positive patients. We tried to present how the SARS-CoV-2 virus can induce thromboembolic events and the incidence of these thromboembolic events. We also tried to depict anticoagulation management in these patients as well as postdischarge plan and follow-up. Invasion of type 2 pneumocytes by the SARS-CoV-2 virus is critical in the course of illness because it results in activation of immune cells leading to elevation of cytokines. The subsequent activation of T cells and macrophages infiltrates the infected myocardial cells causing direct myocardiocyte toxicity and development of arrhythmia. Hypoxia or hypotension during the clinical course causes a mismatch between myocyte oxygen supply and workload demand resulting in cardiac distress. SARS-CoV-2 affects endothelial cells and pericytes that lead to severe micro and macrovascular dysfunction, and together with oxygen supply-demand mismatch, immune hyperresponsivity can potentially cause destabilization and plaque rupture causing acute coronary syndromes. Other mechanisms of injury include myocarditis, pericarditis, stress cardiomyopathy, vasculitis, and DIC (Disseminated intravascular coagulation)/microthrombi. SARS-CoV-2 enters the cells by the Spike protein S whose surface unit, S1, binds to the ACE2 receptor on the host cell. The type II transmembrane serine proteases TMPRSS2 and histone acetyltransferases (HAT) are host cell proteases that are recruited by the virus to cleave ACE2 surface protein S which facilitates the viral entry. Therefore, TMPRSS2 and HAT could be targeted for potential drugs against SARS-CoV-2. SARS-CoV-2 uses an RNA-dependent RNA polymerase for proliferation, which is targeted by remdesivir that is currently approved for emergency use by Food and Drug Administration (FDA). We need to adopt a multifaceted approach when combating SARS-CoV-2 because it presents several challenges including medical, psychological, socioeconomic, and ethical. COVID-19 is the biggest calamity during the 21st century, we need to have a keen understanding of its pathophysiology and clinical implications for the development of preventive measures and therapeutic modalities.

Project description:Objectives: This study aimed to explore the relationship between glycaemic control and factors that may influence this among elderly type 2 diabetes mellitus (T2DM) patients in Lahore, Pakistan. Methods: This descriptive, cross-sectional study was conducted at the Jinnah and Sir Ganga Ram Hospitals, Lahore using convenience sampling techniques between 1 December 2015 and 28 February 2016. The sample consisted of elderly (>65 years) T2DM patients. Glycaemic values and patient characteristics were obtained from medical charts. Consenting patients were interviewed to complete the Barthel Index, Lawton Instrumental Activities of Daily Living Scale, Clinical Frailty Scale, Iowa Pain Thermometer Scale, Geriatric Depression Scale, Montreal Cognitive Assessment tool, Mini Nutritional Assessment Scale-Short Form and Self Care Inventory-Revised Version. Multiple logistic regression analysis was carried out to determine the predictors of poor glycaemic control. Results: A total of 490 patients were approached and 400 agreed to participate. Overall, nearly one-third (32.2%, n = 129) of patients had glycated haemoglobin (HbA1c) at the target level. Fasting and random plasma glucose levels were within the target range to much the same extent; (36.8%, n = 147) and (27%, n = 108), respectively. HbA1c levels were also higher in patients with co-morbidities (67.4%, n = 229) with diabetes-related complications (73.5%, n = 227). Significant predictors of impaired glycaemic control (HbA1c) included poor diabetes self-care (adjusted odds ratio (AOR) 0.96; 95% confidence interval (CI) 0.95, 0.98), not being prescribed oral hypoglycaemic agents (OHA) (AOR 6.22; 95% CI 2.09, 18.46), regular hypoglycaemic attacks (AOR 2.53; 95% CI 1.34, 4.81) and falling tendency (AOR 0.19; 95% CI 0.10, 0.36). Conclusions: Poor glycaemic control prevailed among the majority of elderly Pakistani diabetic patients in this study. Triggering factors of poor glycaemic control should be taken into consideration by the healthcare professionals in targeting multifaceted interventions to achieve good glycaemic control.

Project description:BACKGROUND:Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III. METHODS:This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method. RESULTS:There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 ?g/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 ?g/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41?g/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status. CONCLUSION:Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients.

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Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

Publications

Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

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