Glycemic Control and Plasma Levels of Pro-Inflammatory and Pro-Thrombotic Biomarkers in Diabetic Patients Presenting with Acute Pulmonary Embolism

Abstract

Type I and type II diabetes are closely associated with a pro-inflammatory state and to a pro-thrombotic state. The role of glycemic control in pulmonary embolism (PE) is poorly understood and requires additional investigation. The aim of this study is to investigate the relationship between glycemic control and thrombo-inflammatory biomarkers in a PE patient cohort compared to normal samples. Demographic and clinical information for 86 diabetic patients and 106 non-diabetic patients presenting with acute PE was collected via retrospective chart review. Plasma levels of pro-inflammatory (C-reactive protein [CRP], tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and pro-thrombotic (d-dimer, plasminogen activator inhibitor-1 [PAI-1], tissue plasminogen activator [tPA], thrombin activatable fibrinolysis inhibitor [TAFI], von-Willebrand factor [vWF], endogenous glycosaminoglycans [GAGs]) biomarkers were drawn within 24 hours of diagnosis of acute PE. Data was also obtained for a population of healthy adult controls. All the pro-inflammatory and pro-thrombotic biomarkers were elevated in diabetic PE patients in comparison to healthy controls. None of the biomarkers were elevated in diabetic PE patients when compared to non-diabetic PE patients. There was no difference in the levels of the pro-inflammatory biomarkers according to glycemic control. The plasma level of TAFI was elevated in diabetic patients with poor glycemic control. Diabetic patients were more likely to have a more severe PE. These studies demonstrate that thrombo-inflammatory biomarkers are elevated in diabetic PE patients with associated comorbidities in comparison to normal individuals. However, there is no difference between the PE cohort alone in comparison to PE with diabetes. The role of TAFI within the continuum of diabetic vascular disease warrants additional investigation.

Hemostatic tests in patients with type 2 diabetes mellitus

“…(12,14) Este proceso provoca una menor producción de plasmina gracias a la inhibición de la t-PA, lo que conlleva a un estado protrombótico e inflamatorio. (12) Asimismo, la DM2 estimula a la elevación de factores antifibrinolíticos como son el PAI y TAFI, (7,15) cuyos componentes afectan a los factores fibrinolíticos, sin embargo, estos cambios están vinculados a los niveles de glucemia y podrían ser revertidos mediante un énfasis en el control glucémico. (15) Salud, Ciencia y Tecnología.…”

“…(12) Asimismo, la DM2 estimula a la elevación de factores antifibrinolíticos como son el PAI y TAFI, (7,15) cuyos componentes afectan a los factores fibrinolíticos, sin embargo, estos cambios están vinculados a los niveles de glucemia y podrían ser revertidos mediante un énfasis en el control glucémico. (15) Salud, Ciencia y Tecnología. 2024; 4:981 4…”

“…Su incremento podría estar asociado con la estimulación de citoquinas inflamatorias (TNF-α, IL-1), pues conviene mencionar que la resistencia a la insulina e hiperglicemia contribuyen a un estado inflamatorio y por tanto, puede verse aumentada la producción de citocinas y mayor expresión de PAI-1. (15,28) El PAI-1 junto con TAFI, pueden contribuir a una fibrinólisis deficiente, ya que inhiben directamente los activadores del plasminógeno y reducen los lugares de unión del tPA (activador tisular del plasminógeno)/ plasminógeno. (15) Los resultados de investigaciones han sido controversiales, pues, si bien algunos demuestran relación entre el TAFI y la diabetes, otros demuestran que la hiperglicemia y resistencia a la insulina, no afectan en el mismo.…”

“…(15,28) El PAI-1 junto con TAFI, pueden contribuir a una fibrinólisis deficiente, ya que inhiben directamente los activadores del plasminógeno y reducen los lugares de unión del tPA (activador tisular del plasminógeno)/ plasminógeno. (15) Los resultados de investigaciones han sido controversiales, pues, si bien algunos demuestran relación entre el TAFI y la diabetes, otros demuestran que la hiperglicemia y resistencia a la insulina, no afectan en el mismo. (15,16,31) Además, se ha documentado un incremento en los niveles del FvW en diabéticos a diferencia de pacientes control, tal como se muestra en la Tabla 1.…”

The Cellular and Protein Arms of Coagulation in Diabetes: Established and Potential Targets for the Reduction of Thrombotic Risk

“…Finally, high glucose levels can result in plasminogen glycation that affects conversion to plasmin and also compromises the enzymatic efficiency of the protein [83]. Circulating levels of other antifibrinolytic proteins such as TAFI have been found to be significantly greater in those with diabetes when compared to healthy controls, particularly in patients with obesity [84], and higher levels of TAFI correlate with greater thrombotic risk [85,86], including in those with poor glycaemic control [87].…”