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DOI: 10.1055/s-0030-1270072
Hemostatic Disorders in Type 1 Diabetes Mellitus
Publication History
Publication Date:
19 January 2011 (online)
ABSTRACT
This review summarizes current knowledge of the adverse effects of type 1 diabetes mellitus on coagulation and fibrinolysis. Although further larger studies are needed to provide more definitive information, patients with type 1 diabetes exhibit a proinflammatory/procoagulant condition deriving from increased platelet adhesiveness, activation of the coagulation system, and decreased plasma fibrinolytic potential. This review also focuses on recent data from large prospective studies suggesting a strong association between procoagulant imbalance and development of chronic vascular complications in people with type 1 diabetes. It is likely that a greater appreciation of the intimate interactions between endothelial integrity, coagulation and fibrinolytic factors, and platelets in type 1 diabetes will provide a greater understanding of the risk of developing cardiovascular disease and microvascular complications such as nephropathy and retinopathy in this patient population.
KEYWORDS
Type 1 diabetes - coagulation - fibrinolysis - hemostatic disorders
REFERENCES
- 1 American Diabetes Association . Standards of medical care in diabetes—2010. Diabetes Care. 2010; 33 ((Suppl 1)) S11-S61
- 2 Eckel R H, Wassef M, Chait A et al.. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II: pathogenesis of atherosclerosis in diabetes. Circulation. 2002; 105 (18) e138-e143
- 3 Franchini M, Targher G, Montagnana M, Lippi G. The metabolic syndrome and the risk of arterial and venous thrombosis. Thromb Res. 2008; 122 (6) 727-735
- 4 Mina A, Favaloro E J, Koutts J. Hemostatic dysfunction associated with endocrine disorders as a major risk factor and cause of human morbidity and mortality: a comprehensive meta-review. Semin Thromb Hemost. 2007; 33 (8) 798-809
- 5 Targher G, Chonchol M, Miele L, Zoppini G, Pichiri I, Muggeo M. Nonalcoholic fatty liver disease as a contributor to hypercoagulation and thrombophilia in the metabolic syndrome. Semin Thromb Hemost. 2009; 35 (3) 277-287
- 6 Blann A D, Lip G Y. Endothelial integrity, soluble adhesion molecules and platelet markers in type 1 diabetes mellitus. Diabet Med. 1998; 15 (8) 634-642
- 7 el Khawand C, Jamart J, Donckier J et al.. Hemostasis variables in type I diabetic patients without demonstrable vascular complications. Diabetes Care. 1993; 16 (8) 1137-1145
- 8 Yngen M, Ostenson C G, Hu H, Li N, Hjemdahl P, Wallén N H. Enhanced P-selectin expression and increased soluble CD40 Ligand in patients with type 1 diabetes mellitus and microangiopathy: evidence for platelet hyperactivity and chronic inflammation. Diabetologia. 2004; 47 (3) 537-540
- 9 Devaraj S, Glaser N, Griffen S, Wang-Polagruto J, Miguelino E, Jialal I. Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes. 2006; 55 (3) 774-779
- 10 Davì G, Chiarelli F, Santilli F et al.. Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration. Circulation. 2003; 107 (25) 3199-3203
- 11 Hu H, Li N, Yngen M, Ostenson C G, Wallén N H, Hjemdahl P. Enhanced leukocyte-platelet cross-talk in type 1 diabetes mellitus: relationship to microangiopathy. J Thromb Haemost. 2004; 2 (1) 58-64
- 12 Haitas B, Barnes A J, Cederholm-Williams S A, Moore J, Shogry M E, Turner R C. Abnormal endothelial release of fibrinolytic activity and fibronectin in diabetic microangiopathy. Diabetologia. 1984; 27 (5) 493-496
- 13 Carmassi F, Morale M, Puccetti R et al.. Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. Thromb Res. 1992; 67 (6) 643-654
- 14 Reverter J L, Reverter J C, Tàssies D et al.. Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus. Am J Hematol. 1997; 56 (2) 93-99
- 15 Fasching P, Veitl M, Rohac M et al.. Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1996; 81 (12) 4313-4317
- 16 Targher G, Bertolini L, Zoppini G, Zenari L, Falezza G. Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in type 1 diabetic patients without clinically manifest macroangiopathy. Diabet Med. 2005; 22 (8) 999-1004
- 17 Smulders R A, Stehouwer C D, Schalkwijk C G, Donker A J, van Hinsbergh V W, TeKoppele J M. Distinct associations of HbA1c and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus. Thromb Haemost. 1998; 80 (1) 52-57
- 18 Giusti C, Schiaffini R, Brufani C, Pantaleo A, Vingolo E M, Gargiulo P. Coagulation pathways and diabetic retinopathy: abnormal modulation in a selected group of insulin dependent diabetic patients. Br J Ophthalmol. 2000; 84 (6) 591-595
- 19 Elhadd T A, Kennedy G, Hill A et al.. Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease. Diabetes Metab Res Rev. 1999; 15 (6) 405-411
- 20 Zoppini G, Targher G, Cacciatori V, Guerriero A, Muggeo M. Chronic cigarette smoking is associated with increased plasma circulating intercellular adhesion molecule 1 levels in young type 1 diabetic patients. Diabetes Care. 1999; 22 (11) 1871-1874
- 21 Schalkwijk C G, Poland D C, van Dijk W et al.. Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia. 1999; 42 (3) 351-357
- 22 Rathcke C N, Persson F, Tarnow L, Rossing P, Vestergaard H. YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care. 2009; 32 (2) 323-328
- 23 Romano M, Pomilio M, Vigneri S et al.. Endothelial perturbation in children and adolescents with type 1 diabetes: association with markers of the inflammatory reaction. Diabetes Care. 2001; 24 (9) 1674-1678
- 24 Antovic J P, Yngen M, Ostenson C G et al.. Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications. Blood Coagul Fibrinolysis. 2003; 14 (6) 551-556
- 25 Harmanci A, Kandemir N, Dagdelen S et al.. Thrombin-activatable fibrinolysis inhibitor activity and global fibrinolytic capacity in type 1 diabetes: evidence for normal fibrinolytic state. J Diabetes Complications. 2006; 20 (1) 40-44
- 26 Leurs P B, van Oerle R, Hamulyak K, Wolffenbuttel B H. Tissue factor pathway inhibitor activity in patients with IDDM. Diabetes. 1995; 44 (1) 80-84
- 27 Iorio A, Federici M O, Mourvaki E et al.. Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type 1 diabetic patients. Thromb Haemost. 2007; 98 (3) 635-641
- 28 Rigla M, Mateo J, Fontcuberta J, Souto J C, de Leiva A, Pérez A. Normalisation of tissue factor pathway inhibitor activity after glycaemic control optimisation in type 1 diabetic patients. Thromb Haemost. 2000; 84 (2) 223-227
- 29 Franklin V L, Khan F, Kennedy G, Belch J J, Greene S A. Intensive insulin therapy improves endothelial function and microvascular reactivity in young people with type 1 diabetes. Diabetologia. 2008; 51 (2) 353-360
- 30 Schönbeck U, Libby P. CD40 signaling and plaque instability. Circ Res. 2001; 89 (12) 1092-1103
- 31 Harding S A, Sommerfield A J, Sarma J et al.. Increased CD40 ligand and platelet-monocyte aggregates in patients with type 1 diabetes mellitus. Atherosclerosis. 2004; 176 (2) 321-325
- 32 Varo N, Vicent D, Libby P et al.. Elevated plasma levels of the atherogenic mediator soluble CD40 ligand in diabetic patients: a novel target of thiazolidinediones. Circulation. 2003; 107 (21) 2664-2669
- 33 Targher G, Zoppini G. Soluble CD40L in young type 1 diabetic individuals without clinical microvascular and macrovascular complications. Diabetes Care. 2004; 27 (5) 1236-1237
- 34 Sabatier F, Darmon P, Hugel B et al.. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes. 2002; 51 (9) 2840-2845
- 35 Sibal L, Aldibbiat A, Agarwal S C et al.. Circulating endothelial progenitor cells, endothelial function, carotid intima-media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia. 2009; 52 (8) 1464-1473
- 36 Goldberg R B. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab. 2009; 94 (9) 3171-3182
- 37 Costacou T, Lopes-Virella M F, Zgibor J C The Pittsburgh Epidemiology of Diabetes Complications Study et al. Markers of endothelial dysfunction in the prediction of coronary artery disease in type 1 diabetes. J Diabetes Complications. 2005; 19 (4) 183-193
- 38 Astrup A S, Tarnow L, Pietraszek L et al.. Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortality and decline of glomerular filtration rate. Diabetes Care. 2008; 31 (6) 1170-1176
- 39 Lin J, Glynn R J, Rifai N et al.. Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial. Diabetes Care. 2008; 31 (12) 2338-2343
- 40 Lopes-Virella M F, Carter R E, Gilbert G E Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Cohort Study Group et al. Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications. Diabetes Care. 2008; 31 (10) 2006-2012
- 41 Soedamah-Muthu S S, Chaturvedi N, Pickup J C, Fuller J H. EURODIAB Prospective Complications Study Group . Relationship between plasma sialic acid and fibrinogen concentration and incident micro- and macrovascular complications in type 1 diabetes. Diabetologia. 2008; 51 (3) 493-501
- 42 Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005; 54 (6) 1615-1625
Giovanni TargherM.D.
Section of Endocrinology, Department of Medicine, University of Verona
Ospedale Civile Maggiore, Piazzale Stefani, 1, 37126 Verona, Italy
Email: giovanni.targher@univr.it