Diabetes and atherothrombosis: The circadian rhythm and role of melatonin in vascular protection.

Publisher: Sage Publications Country of Publication: England NLM ID: 101234011 Publication Model: Print Cited Medium: Internet ISSN: 1752-8984 (Electronic) Linking ISSN: 14791641 NLM ISO Abbreviation: Diab Vasc Dis Res Subsets: MEDLINE

Publication: 2009- : London : Sage Publications
Original Publication: Edgbaston, Birmingham, UK : Sherborne Gibbs, c2005-

Circadian Rhythm*; Atherosclerosis/*blood ; Diabetes Mellitus, Type 2/*blood ; Melatonin/*blood ; Thrombosis/*blood; Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/etiology ; Atherosclerosis/physiopathology ; Blood Coagulation ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/physiopathology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Fibrinolysis ; Humans ; Insulin Resistance ; Melatonin/deficiency ; Melatonin/therapeutic use ; Secretory Pathway ; Signal Transduction ; Thrombosis/drug therapy ; Thrombosis/etiology ; Thrombosis/physiopathology

Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease. The disruption of circadian cycles in man secondary to chronic obesity and loss of circadian cues is implicated in the increased risk of developing diabetes and cardiovascular disease. Levels of melatonin, the endogenous synchronizer of circadian rhythm, are reduced in individuals with vascular disease and those with deranged glucose metabolism. The anti-inflammatory, antihypertensive, antioxidative and antithrombotic activities of melatonin make it a potential therapeutic agent to reduce the risk of vascular occlusive disease in diabetes. The mechanisms behind melatonin-associated reduction in procoagulant response are not fully known. Current evidence suggests that melatonin inhibits platelet aggregation and might affect the coagulation cascade, altering fibrin clot structure and/or resistance to fibrinolysis. Large-scale clinical trials are warranted to investigate the effects of modulating the circadian clock on insulin resistance, glycaemia and cardiovascular outcome.

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Keywords: Diabetes; freestyle libre; hypoglycaemia; interstitial fluid glucose; mean average relative difference

JL5DK93RCL (Melatonin)

Date Created: 20200609 Date Completed: 20200925 Latest Revision: 20240330

20240330

PMC7607413

10.1177/1479164120920582

32506946