Peripheral artery disease in type 2 diabetes: the role of fibrinolysis

Summary

The aim of the present study is to verify the relationship between peripheral artery disease (PAD) and some coagulation/fibrinolysis parameters in type 2 diabetic patients.

Sixty-three type 2 diabetic patients, without PAD, were studied at baseline and after 4 years. Assessments included tissue-Plasminogen Activator (t-PA), Plasminogen Activator Inhibitor-1 antigen (PAI-1 Ag), Plasminogen Activator Inhibitor-1 activity (PAI-1 Act), Plasminogen (Pl), Fibrin peptide A (FPA), Fibrinogen (Fr), and the ankle/brachial pressure index (ABI).

We observed a significant difference between diabetic patients and controls as regards tPA (11.8 ± 5.4 vs. 6.6 ± 3.0 ng/ml; p <0.05 ) and PAI-1 Act (17.8 ± 9.2 vs. 11.7 ± 6.6 ng/dl; p <0.005). After 4 years 13 diabetic patients became vasculo-pathic and, at baseline, had significantly lower tPA (8.9 ± 4.8 vs. 12.5 ± 5.3; p <0.011), and higher PAI-1 Ag (50.8 ± 22.2 vs. 32 ± 22.2; p <0.006), and PAI-1 Act values (24.1 ± 9.5 vs. 16.1 ± 8.4; p <0.014), compared with 50 diabetic patients who did not develop PAD after 4 years.

These data show that the physiological equilibrium which exists between t-PA and PAI-1 moves towards higher levels in our diabetic patients compared with controls, at baseline, whereas diabetic patients who developed PAD showed a shift towards an antifibrinolytic pathway with diminished t-PA, increased PAI-1 Ag and PAI-1 Act and consequently procoagulant activity. Our study suggests that hypofibrinolysis may be involved in the future onset of PAD in type 2 diabetic patients.

Keywords

Peripheral artery disease - fibrinolysis - diabetes

• References

• 1 Kannel WB, Mc Gee DL. Diabetes and cardiovascular disease. JAMA 1979; 241: 2035-8.
• 2 Hooi JD, Kester ADM, Stoffers HEJH, Overdijk MM, van Ree JW, Knottneurus JA. Incidence of and risk factors for asyntomatic arterial occlusive disease: a longitudinal study. Am J Epidemiol 2001; 153 (07) 666-72.
• 3 Jude EB, Oyibo SO, Chalmers N, Boulton AJ. Peripheral arterial disease in diabetic and non diabetic patients: a comparison of severity and outcome. Diabetes Care 2001; 24 (08) 1433-7.
• 4 Leng GC, Fowkes FG, Lee AJ, Dunbar J, Housley E, Ruckley CV. Use of ankle brachial pressure index to predict cardiovascular events and death: a cohort study. BMJ 1996; 313 7070 1440-4.
• 5 1999 World Health Organization – International Society of Hypertension. Guidelines for the Management of Hypertension. Guidelines Subcommitee. J Hypertens 1999; 17 (02) 151-83.
• 6 Mogensen CE, Chachati A, Christensen CK, Close CF, Deckert T, Hommel E, Kastrup J, Lefebvre P, Mathiesen ER, Feldt-Rasmussen B. Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest 1985; 1986; 9 (02) 85-95.
• 7 Rose G. The diagnosis of ischemic heart pain and intermittent claudication in field surveys. Bull WHO 1962; 27: 645-58.
• 8 Yao JST.. Pressure measurement in the extremity. In: Vascular diagnosis. Bernstein EF, Editor. 4th ed. St Louis, Missouri: Mosby; 1993: 169-75.
• 9 Sumner D.. Volume plethysmography in vascular disease: an overview. In Vascular diagnosis. 4th ed. Bernstein EF, Editor. St Louis, Missouri: Mosby; 1993: 181-93.
• 10 Fowkes FGR. The measurement of atherosclerotic peripheral arterial disease in epidemiological surveys. Intern J Epidemiol 1988; 17: 248-54.
• 11 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502.
• 12 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28 (07) 412-9.
• 13 Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23 (01) 57-63.
• 14 Rosner E. Fondamental of biostatistics. In: SAS/STAT User’s guide. 4th ed. Version 8. Cary, NC, SAS Institute: Inc Duxbury; 1999
• 15 Meheler PS, Jeffers WJ, Estacio R, Schrirer RW. Association of hypertension and complications in non insulin-dependent diabetes mellitus. Am J Hypertens 1997; 10: 152-61.
• 16 Mac Gregor AS, Price JF, Hau CM, Lee AJ, Carson MN, Fowkes FG. Role of systolic blood pressure and plasma triglycerides in diabetic peripheral arterial disease. Diabetes Care 1999; 22 (03) 453-8.
• 17 Nelson RG, Gohdes DM, Everhart JE, Hartner JA, Zwemer FL, Pettit DJ, Knowler WC. Lower-extremity amputations in NIDDM. 12-year follow-up study in Pima Indians. Diabetes Care 1988; 11 (01) 8-16.
• 18 Uusitupa MIJ, Niskanen LK, Siitonen O, Voutilainen E, Pyorala K. 5 years incidence of atherosclerotic vascular disease in relation to general risk factors, insulin levels, and abnormalities in lipoprotein composition in non-insulin diabetic and non diabetic subjects. Circulation 1990; 82: 27-36.
• 19 Walters DP, Gatling W, Mullee MA, Hill RD. The prevalence, detection, and epidemiological correlates of peripheral vascular disease: a comparison of diabetic and non-diabetic subjects in an English community. Diabet Med 1992; 9 (08) 710-5.
• 20 Katsilambros NL, Tsapogas PC, Arvanitis MP, Tritos NA, Alexiou ZP, Rigas KL. Risk factors for lower extremity arterial disease in non insulin-dependent diabetic persons. Diabet Med 1996; 13: 243-6.
• 21 Kreines K, Johnson E, Albrink M, Knatterud GL, Levin ME, Lewitan A, Newberry W, Rose FA. The corse of peripheral vascular disease in non-insulin-dependent diabetes. Diabetes Care 1985; 8: 235-43.
• 22 Mc Daniel MD, Cronenwett JL. Basic data related to the natural hystory of intermittent claudicatio. Ann Vasc Surg 1989; 3: 273-7.
• 23 Lee AJ, MacGregor AS, Hau CM, Price JF, Rumley A, Lowe GDO, Fowkes FG. The role of haematological factors in diabetic peripheral arterial disease: the Edinburgh Artery Study. Br J Haematol 1999; 105 (03) 648-54.
• 24 Tkac I, Molcanyiova A. Fibrinogen and albuminuria are related to the presence and severity of peripheral arterial disease in women with type 2 diabetes mellitus. Angio-logy 1997; 48: 715-9.
• 25 Fabsitz RR, Sidawy AN, Go O, Lee ET, Welty TK, Devereux RB, Howard BV. Prevalence of peripheral arterial disease and associated risk factors in American Indians: the Strong Heart Study. Am J Epidemiol 1999; 149 (04) 330-8.
• 26 Missov RM, Stolk RP, van der Bom JG, Hofman A, Bots ML, Pols HA, Groobbee DE. Plasma fibrinogen in NIDDM: the Rotterdam study. Diabetes Care 1996; 19 (02) 157-9.
• 27 Auwerx J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988; 8 (01) 68-72.
• 28 Schneider DJ, Nordt TK, Sobel BE. Attenuated fibrinolysis and accelerated atherogenesis in type II diabetic patients. Diabetes 1993; 42: 1-7.
• 29 Juhan-Vague I, Thompson SG, Jespersen J. Involment of the hemostatic system in the insulin resistence syndrome: a study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group. Arterioscler Thromb 1993; 13 (12) 1865-73.
• 30 Adler IA, Stevens RJ, Neil A, Stratton IM, Boulton AJM, Holman RR. UKPDS 59: Hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabetes Care 2002; 25: 894-9.
• 31 Pahloo A, Yudkin S. Diminished fibrinolysis in diabetes mellitus and its implication for diabetic vascular disease. Coron Artery Dis 1996; 7 (10) 723-31.