Role of complement in diabetes

Abstract

Accumulating evidence suggests a role for the complement system in the pathogenesis of diabetes and the vascular complications that characterise this condition. Complement proteins contribute to the development of type 1 diabetes (T1D) by enhancing the underlying organspecific autoimmune processes. Complement upregulation and activation is also an important feature of insulin resistance and the development of type 2 diabetes (T2D). Moreover, animal and human studies indicate that complement proteins are involved in the pathogenic mechanisms leading to diabetic microvascular and macrovascular complications. The adverse vascular effects of complement appear to be related to enhancement of the inflammatory process and the predisposition to a thrombotic environment, eventually leading to vascular occlusion. Complement proteins have been considered as therapeutic targets to prevent or treat vascular disease but studies have been mainly conducted in animal models, while human work has been both limited and inconclusive so far. Further studies are needed to understand the potential role of complement proteins as therapeutic targets for reversal of the pathological processes leading to T1D and T2D and for the prevention/treatment of diabetic vascular complications.

Persistent Clotting Protein Pathology in Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) is Accompanied by Increased Levels of Antiplasmin

“…SAA1 and Complement C1r subcomponent-like protein were also increased in the fully digested plaama supernatant of T2DM (after a rst trypsinization step), compared to the fully digested plasma supernatant samples from controls. Increases in SAA1 is known in T2DM [44], and adverse vascular effects of complement, the in ammatory process, and a thrombotic environment may play signi cant roles in T2DM pathology [53].…”

Dihydromyricetin Improves Endothelial Dysfunction in Diabetic Mice via Oxidative Stress Inhibition in a SIRT3-Dependent Manner

“…The increasing prevalence of diabetes becomes a serious global health problem [ 1 , 2 , 3 ]. There are various chronic complications of diabetes, which are the main cause of morbidity and mortality of diabetes, including: diabetic nephropathy, neuropathy, retinopathy, lower extremity vascular lesions, and gastroenteropathy [ 4 , 5 , 6 , 7 ]. Prolonged hyperglycemia may impair endothelial function of macro- and micro-vascular to increase risks for cardiovascular disease in diabetes [ 8 , 9 ].…”

Diabetes affects endothelial cell function and alters fibrin clot formation in a microvascular flow model: A pilot study

“…We measured several proteins of the coagulation/fibrinolysis (fibrinogen, PAI-1) 20,21 and complement system (MBL, C3, sC5b-9) 14,15 that are associated with diabetes and reflect the procoagulant and proinflammatory state. Fructosamine is a marker for non-enzymatic protein glycation.…”

“…The complement system, a part of the innate immune system that fights infection but also boosts inflammatory reactions, is emerging as a player in diabetes. 14,15 The complement system also closely interacts with the coagulation and fibrinolytic system, further promoting clot formation. 16 In diabetes patients, elevated plasma levels of complement proteins and activation products were associated with increased clot formation, denser clot structure and prolonged clot lysis.…”