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

Abstract

Diabetes is a metabolic condition with a rising global prevalence and is characterised by abnormally high blood glucose levels. Cardiovascular disease (CVD) accounts for the majority of deaths in diabetes and, despite improvements in therapy, mortality and hospitalisations in this cohort remain disproportionally higher compared to individuals with normal glucose metabolism. One mechanism for increased CVD risk is enhanced thrombosis potential, due to altered function of the cellular and acellular arms of coagulation. Different mechanisms have been identified that mediate disordered blood clot formation and breakdown in diabetes, including dysglycaemia, insulin resistance, and metabolic co-morbidities. Collectively, these induce platelet/endothelial dysfunction and impair the fibrinolytic process, thus creating a prothrombotic milieu. Despite these abnormalities, current antithrombotic therapies are largely similar in diabetes compared to those without this condition, which explains the high proportion of patients experiencing treatment failure while also displaying an increased risk of bleeding events. In this narrative review, we aimed to summarise the physiological functioning of haemostasis followed by the pathological effects of diabetes mellitus on platelets and the fibrin network. Moreover, we carefully reviewed the literature to describe the current and future therapeutic targets to lower the thrombosis risk and improve vascular outcomes in diabetes.

Short, frequent, light‐intensity walking activity improves postprandial vascular‐inflammatory biomarkers in people with type 1 diabetes: The SIT‐LESS randomized controlled trial

“…Cardiovascular complications in T1D are driven by an enhanced inflammatory/thrombotic milieu and are characterized by raised levels and activities of procoagulant proteins as well as compromised function of the fibrinolytic system, 4 thereby increasing the risk of vascular occlusive events. Plasma levels of prothrombotic, including fibrinogen, and antifibrinolytic factors, such as PAI‐1, are increased in people with diabetes, 10,11,25 particularly in T2D and T1D with associated IR 4,10,25 . In the present study, postprandial fibrinogen increased by 61% and PAI‐1 by 49% under SIT, showing the acute deleterious impact of prolonged sitting in this population.…”

“…Sedentary behaviours, including prolonged periods of uninterrupted sitting, are prevalent in type 1 diabetes (T1D) 1 and increase cardiovascular risk 2,3 . A number of inflammatory and thrombotic molecules have been implicated in cardiovascular pathology, including tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, plasminogen activator inhibitor (PAI)‐1 and fibrinogen 4 . Data from previous studies indicate that sitting for prolonged periods predisposes to an adverse cardiovascular inflammatory/metabolic environment, 5 including poorer glucose control, 6 insulin resistance 7 and an increased vascular‐inflammatory milieu 8,9 .…”