Blood coagulation and fibrinolysis before and after exhaustive exercise in patients with IDDM

Summary

Diabetes mellitus involves changes in haemostasis which leads to the opinion that diabetes mellitus is a hypercoagulable state. However, little is known about the relationship of exercise and haemostasis in diabetics. Therefore, first of all the aim was to investigate if differences in blood coagulation and fibrinolysis can be demonstrated in subjects with insulin-dependent diabetes mellitus (IDDM) compared to controls and secondly, if differences concerning exercise induced changes can be seen in diabetics. 16 moderately fit subjects with IDDM and 16 matched controls underwent a maximal step test. Blood samples were taken after a 30 min rest, immediately and 1h after exercise and in addition after 30 min rest 7 days later at the same time of day. The rest values (mean of the two rest samples) in extrinsic total thrombin potential (TTPex, P=0.049), tPA-activity (P=0.007) were significantly higher and in PAI-1-antigen (P=0.002) -activity (P=0.049) lower in the diabetic group. APTT, PT, TAT (only control), TTPin, tPA-activity and -antigen and PAP were increased immediately and D-dimer (only control) 1 h after exercise, whereas PAI-1-activity and -antigen (only control) decreased immediately or 1 h after exercise (all minimal P<0.05). The increase of tPA-antigen and decrease in PAI-1-antigen after exercise were both lower in the diabetics (P<0.05).

IDDM led to higher extrinsic total thrombin and fibrinolytic potential at rest, and reducing the exercise provoked distribution of tPA-antigen and decrease of PAI-1-antigen. Nevertheless a higher thrombotic risk after maximal exercise has not been investigated in young IDDM patients without complications and in good metabolic control.

Keywords

TAT - F1+2 - thrombin potential - tPA - PAI-1

• References

• 1 Takahashi H, Tsuda A, Tatewaki W. et al. Activation of blood coagulation and fibrinoly-sis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex. Thromb Res 1989; 55: 727-35.
• 2 Carr ME. Diabetes mellitus: a hypercoagulable state. J Diabetes Complications 2001; 15: 44-54.
• 3 Acang N, Jalil FD. Hypercoagulation in diabetes mellitus. Southeast Asian J Trop Med Public Health 1993; 24 (01) Suppl 263-6.
• 4 Reverter JL, Reverter JC, Tassies 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: 93-9.
• 5 Yokoyama H, Myrup B, Rossing P. et al. Increased tissue factor pathway inhibitor activity in IDDM patients with nephropathy. Diabetes Care 1996; 19: 441-5.
• 6 Davi G, Gennaro F, Spatola A. et al. Thrombin-antithrombin III complexes in type II diabetes mellitus. J Diabetes Complications 1992; 6: 7-11.
• 7 Morishita E, Asakura H, Jokaji H. et al. Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996; 120: 7-14.
• 8 Lopez Y, Paloma MJ, Rifon J. et al. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res 1999; 93: 71-8.
• 9 Sumida Y, Wada H, Fujii M. et al. Increased soluble fibrin monomer and soluble thrombomodulin levels in non-insulin-dependent diabetes mellitus. Blood Coagul Fibrinolysis 1997; 8: 303-7.
• 10 Van Wersch JW, Westerhuis LW, Venekamp WJ. Coagulation activation in diabetes mellit-us. Haemostasis 1990; 20: 263-9.
• 11 Hemker HC, Wielders S, Kessels H. et al. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thromb Haemost 1993; 70: 617-24.
• 12 Aso Y, Fujiwara Y, Tayama K. et al. Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes. Clin Chim Acta 2000; 301: 135-45.
• 13 Wieczorek I, Pell AC, McIver B. et al. Coagulation and fibrinolytic systems in type I diabetes: effects of venous occlusion and insulin-induced hypoglycaemia. Clin Sci (Lond) 1993; 84: 79-86.
• 14 Takada Y, Urano T, Watanabe I. et al. Changes in fibrinolytic parameters in male patients with type 2 (non-insulin-dependent) diabetes mellitus. Thromb Res 1993; 71: 405-15.
• 15 Brandenburg SL, Reusch JE, Felder KK. et al. Impaired fibrinolysis in premenopausal women and age-matched men with Type 2 diabetes mellitus: a pilot study. J Investig Med 2002; 50: 110-5.
• 16 Sharma SC. Platelet adhesiveness, plasma fibrinogen, and fibrinolytic activity in juvenile-onset and maturity-onset diabetes mellit-us. J Clin Pathol 1981; 34: 501-3.
• 17 Leurs PB, Stolk RP, Hamulyak K. et al. Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes. Diabetes Care 2002; 25: 1340-5.
• 18 Cho YW, Yang DH, Oh DY. et al. Plasma t-PA and PAI-1 antigen concentrations in non-insulin dependent diabetic patients: implication for diabetic retinopathy. Diabetes Res Clin Pract 1994; 22: 123-8.
• 19 Walmsley D, Hampton KK, Grant PJ. Contrasting fibrinolytic responses in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes. Diabet Med 1991; 8: 954-9.
• 20 Vicari AM, Vigano D’Angelo S, Testa S. et al. Normal tissue plasminogen activator and plasminogen activator inhibitor activity in plasma from patients with type 1 diabetes mellitus. Horm Metab Res 1992; 24: 516-9.
• 21 Weiss C, Seitel G, Bartsch P. Coagulation and fibrinolysis after moderate and very heavy exercise in healthy male subjects. Med Sci Sports Exerc 1998; 30: 246-51.
• 22 Bartsch P, Welsch B, Albert M. et al. Balanced activation of coagulation and fibrinolysis after a 2-h triathlon. Med Sci Sports Exerc 1995; 27: 1465-70.
• 23 Hilberg T, Nowacki PE, Muller-Berghaus G. et al. Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives. J Sci Med Sport 2000; 3: 383-90.
• 24 Hilberg T, Prasa D, Sturzebecher J. et al. Thrombin potential and thrombin generation after exhaustive exercise. Int J Sports Med 2002; 23: 500-4.
• 25 Dunstan DW, Mori TA, Puddey IB. et al. A randomised, controlled study of the effects of aerobic exercise and dietary fish on coagulation and fibrinolytic factors in type 2 diabetics. Thromb Haemost 1999; 81: 367-72.
• 26 Ibbotson SH, Gough SC, Rice PJ. et al. The effect of short-term exercise on plasma procoagulant activity in patients with type II (non-insulin-dependent) diabetes and healthy volunteers. Thromb Res 1993; 71: 149-58.
• 27 Schneider SH, Kim HC, Khachadurian AK. et al. Impaired fibrinolytic response to exercise in type II diabetes: effects of exercise and physical training. Metabolism 1988; 37: 924-9.
• 28 Stegmann H, Kindermann W, Schnabel A. Lactate kinetics and individual anaerobic threshold. Int J Sports Med 1981; 2: 160-5.
• 29 Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974; 37: 247-8.
• 30 Prasa D, Svendsen L, Sturzebecher J. Inhibition of thrombin generation in plasma by inhibitors of factor Xa. Thromb Haemost 1997; 78: 1215-20.
• 31 Prasa D, Svendsen L, Sturzebecher J. The ability of thrombin inhibitors to reduce the thrombin activity generated in plasma on extrinsic and intrinsic activation. Thromb Haemost 1997; 77: 498-503.
• 32 Garcia Frade LJ, de la Calle H, Alava I. et al. Diabetes mellitus as a hypercoagulable state: its relationship with fibrin fragments and vascular damage. Thromb Res 1987; 47: 533-40.
• 33 Williams E, Timperley WR, Ward JD. et al. Electron microscopical studies of vessels in diabetic peripheral neuropathy. J Clin Pathol 1980; 33: 462-70.
• 34 Hemker HC, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 1995; 74: 134-8.
• 35 Rotteveel RC, Roozendaal KJ, Eijsman L. et al. The influence of oral contraceptives on the time-integral of thrombin generation (throm-bin potential). Thromb Haemost 1993; 70: 959-62.
• 36 Wielders S, Mukherjee M, Michiels J. et al. The routine determination of the endogenous thrombin potential, first results in different forms of hyper- and hypocoagulability. Thromb Haemost 1997; 77: 629-36.
• 37 Ceriello A. Fibrinogen and diabetes mellitus: is it time for intervention trials?. Diabetologia 1997; 40: 731-4.
• 38 Rigla M, Fontcuberta J, Mateo J. et al. Physical training decreases plasma thrombomodulin in type I and type II diabetic patients. Diabetologia 2001; 44: 693-9.
• 39 Carmassi F, Morale M, Puccetti R. et al. Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. Thromb Res 1992; 67: 643-54.
• 40 Kvasnicka J, Skrha J, Perusicova J. et al. [Levels of tissue-type plasminogen activator (T-PA), its inhibitor (PAI-1) and fibrinogen in the blood of patients with type 1 and 2 diabetes mellitus]. Cas Lek Cesk 1996; 20: 174-177.
• 41 Avellone G, Di Garbo V, Cordova R. et al. Blood coagulation and fibrinolysis in obese NIDDM patients. Diabetes Res 1994; 25: 85-92.
• 42 Freeman MS, Mansfield MW, Barrett JH. et al. Insulin resistance: an atherothrombotic syndrome. Thromb Haemost 2003; 89: 161-8.
• 43 Potter van Loon BJ, Kluft C, Radder JK. et al. The cardiovascular risk factor plasmino-gen activator inhibitor type 1 is related to insulin resistance. Metabolism 1993; 42: 945-9.
• 44 Landin K, Tengborn L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med 1990; 227: 273-8.
• 45 Heywood DM, Mansfield MW, Grant PJ. Factor VII gene polymorphisms, factor VII: C levels and features of insulin resistance in non-insulin-dependent diabetes mellitus. Thromb Haemost 1996; 75: 401-6.
• 46 Asplund-Carlson A, Hamsten A, Wiman B. et al. Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men. Diabetologia 1993; 36: 817-25.
• 47 Morale M, De Negri F, Carmassi F. Fibrin(ogen) and diabetes mellitus: don’t forget fibrinolysis. Diabetologia 1997; 40: 735-7.
• 48 Sobel BE, Woodcock-Mitchell J, Schneider DJ. et al. Increased plasminogen activator inhibitor type 1 in coronary artery atherecto-my specimens from type 2 diabetic compared with nondiabetic patients. A potential factor predisposing to thrombosis and its persistance. Circulation 1998; 97: 2213-21.
• 49 Zhang J, Ren S, Sun D. et al. Influence of gly-cation on LDL-induced generation of fibrinolytic regulators in vascular endothelial cells. Arterioscler Thromb Vasc Biol 1998; 18: 1140-8.
• 50 El-Sayed MS. Blood hemostasis in exercise and training. Med Sci Sports Exerc 2000; 32: 918-25.