Hyperglycemia-induced thrombin formation in diabetes : the possible role of oxidative stress

• Published in: Diabetes (New York, N.Y.) Vol. 44; no. 8; pp. 924 - 928
• Main Authors: CERIELLO, A, GIACOMELLO, R, STEL, G, MOTZ, E, TABOGA, C, TONUTTI, L, PIRISI, M, FALLETI, E, BARTOLI, E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.1995
• Subjects: Aged; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Cohort Studies; Complications and side effects; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose Tolerance Test; Glutathione - pharmacology; Glutathione metabolism; Humans; Hyperglycemia; Hyperglycemia - physiopathology; Male; Medical sciences; Oxidative Stress; Physiological aspects; Reference Values; Thrombin; Thrombin - biosynthesis; Thrombin - metabolism; Endocrinopathy; Human; Oxidative stress; Hyperglycemia; Serine endopeptidases; Enzyme; Coagulation; Hydrolases; Thrombin; Antioxidant; Proteinases; Non insulin dependent diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.44.8.924

Diabetes is characterized by the existence of a thrombosis-prone condition, possibly related to hyperglycemia. However, the mechanism linking hyperglycemia to the activation of the coagulation cascade is still unclear. It has been recently suggested that diabetes is accompanied by increased oxidative stress. In this work, the possibility that oxidative stress may be involved in the hyperglycemia-induced coagulation activation has been evaluated. Prothrombin fragment 1 + 2 (F1 + 2), which represents a reliable marker of the amount of thrombin released in the circulation, has been chosen for studying thrombin formation in vivo. In nine type II diabetic patients and in seven healthy control subjects, matched for age and body mass index, three different experiments were performed: oral glucose tolerance test (OGTT), intravenous antioxidant glutathione (GSH) administration for 2 h, and OGTT plus intravenous GSH administration. Samples were drawn at -15 min and every 30 min from 0 to 180 min. During the OGTT, F1 + 2 significantly increased in both diabetic and healthy subjects. GSH administration during OGTT normalized this phenomenon. GSH administration alone significantly decreased F1 + 2 in diabetic patients, while no effect was observed in the normal subjects. These data suggest that hyperglycemia may induce thrombin activation, possibly inducing an oxidative stress, and that antioxidant GSH may counterbalance this effect.