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A significant relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus without complications

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International Journal of Clinical and Laboratory Research

Abstract

We previously found a relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus and hypothesized that this could be due to a compensatory mechanism able to lower the risk of hypofibrinolysis found in type II diabetes mellitus. The aims of the present study were: (1) to confirm the association between plasminogen activator inhibitor type-1 and lipoprotein(a) in a different group of non-insulin-dependent diabetes mellitus patients and (2) to investigate whether the association could be related to diabetic complications. Other vascular risk factors able to influence fibrinolytic parameters such as glycemia, obesity, hypertension, dyslipidemia, and oxidative stress were also considered. Sixty-six non-insulin-dependent diabetes mellitus patients without diabetic complications (48 men, 18 women), 45 non-insulin-dependent diabetes mellitus patients with complications (21 men, 24 women), and 31 control subjects (17 men, 14 women) were studied. Plasma concentrations of lipoprotein(a), plasminogen activator inhibitor type-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Antioxidant defense was assayed as oxygen radical absorbance capacity of serum. Statistically significant differences among controls and the two diabetic groups were found for fasting glucose, cholesterol, triglycerides, and oxygen radical absorbance capacity of serum, while no statistically significant differences were evident for plasminogen activator inhibitor type-1 antigen and activity and lipoprotein(a). Regression analysis of log plasminogen activator inhibitor type-1/lipoprotein(a) showed a significant correlation only in diabetic patients without complications (r=−0.57,P<0.001). These results show that a relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) is characteristic of a diabetic population without complications, supporting the suggestion that this relationship could be a compensatory mechanism of the fibrinolytic system to limit the risks of hypofibrinolysis. A lack or a loss of capacity to balance lipoprotein(a) and plasminogen activator inhibitor type-1 could contribute to the pathogenesis of the diabetic complications.

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References

  1. Wiman B, Hamsten A. The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease. Semin Thromb Hemost 1990; 16:207.

    PubMed  CAS  Google Scholar 

  2. Smith EB. Haemostatic factors and atherogenesis. Atherosclerosis 1996; 124:137.

    Article  PubMed  CAS  Google Scholar 

  3. Schneider DJ, Nordt TK, Sobel BE. Attenuated fibrinolysis and accelerated atherogenesis in type II diabetic patients. Diabetes 1993; 42:1.

    Article  PubMed  CAS  Google Scholar 

  4. Levin EG. Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells. Blood 1986; 67:1309.

    PubMed  CAS  Google Scholar 

  5. Sprengers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69:381.

    PubMed  CAS  Google Scholar 

  6. Koschinsky LM, Marcovina SM. Lipoprotein(a): structural implications for pathophysiology. Int J Clin Lab Res 1997; 27:14.

    Article  PubMed  CAS  Google Scholar 

  7. Scanu AM. Lipoprotein(a). Bailleres Clin Endocrinol Metab 1990; 4:939.

    Article  CAS  Google Scholar 

  8. Auwerx J, Bouillon R, Collen D, Geboers J. Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 1988; 8:68.

    PubMed  CAS  Google Scholar 

  9. Hancu N, Netea MG, Iancu S. Serum lipoprotein(a) is increased in hypertensive NIDDM patients. Diabetes Care 1995; 18:879.

    PubMed  CAS  Google Scholar 

  10. Morishita E, Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Yamazaki M, Aoshima K, Hashimoto T, Matsuda T. Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996; 120:7.

    Article  PubMed  CAS  Google Scholar 

  11. Park YS, Park S, Kim SY, Lee HK, Koh CS, Min HK, Kim JQ. The effect of obesity on fibrinolytic activity and plasma lipoprotein(a) levels in patients with type 2 diabetes mellitus in Korea. Diabetes Res Clin Pract 1994; 24:25.

    Article  PubMed  CAS  Google Scholar 

  12. Ho CH, Jap TS. Relationship of plasminogen activator inhibitor-1 with plasma insulin, glucose, triglyceride and cholesterol in Chinese patients with diabetes. Thromb Res 1993; 69:271.

    Article  PubMed  CAS  Google Scholar 

  13. Vukovich T, Schernthaner G. The effect of insulin treatment on the balance between tissue plasminogen activator and plasminogen activator inhibitor-1 in type 2 diabetic patients. Thromb Haemost 1992; 68:253.

    PubMed  CAS  Google Scholar 

  14. Jokaji H, Asakura H, Saito M, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Matsuda T. Tissue-type plasminogen activator and its inhibitor (PAI-1) in plasma in cases of non-insulin-dependent diabetes mellitus (NIDDM). Nippon Ronen Igakkai Zasshi 1990; 27:699.

    PubMed  CAS  Google Scholar 

  15. Joven J, Vilella E. Serum levels of lipoprotein(a) in patients with well controlled non insulin dependent diabetes mellitus. JAMA 1991; 265:1113.

    Article  PubMed  CAS  Google Scholar 

  16. Testa R, Bonfigli AR, Piantanelli L, Manfrini S, Testa I, Gregorio F. Relationship between plasminogen activator inhibitor type I plasma levels and the lipoprotein(a) concentrations in non insulin dependent diabetes mellitus. Diabetes Res Clin Pract 1996; 33:111.

    Article  PubMed  CAS  Google Scholar 

  17. Huisveld IA, Leenen R, Kooy K vd, Hospers JEH, Seidell JC, Deurenberg P, Koppeschaar HPF, Mosterd WL, Bouma BN. Body composition and weight reduction in relation to antigen and activity of plasminogen activator inhibitor (PAI-1) in overweight individuals. Fibrinolysis 1990; 4:84.

    Article  Google Scholar 

  18. Oseroff A, Krishnamurti C, Hassett A, Tang D, Alving B. Plasminogen activator and plasminogen activator inhibitor activities in men with coronary artery disease. J Lab Clin Med 1989; 113:88.

    PubMed  CAS  Google Scholar 

  19. Ceriello A, Curcio F, Russo P dello, Pegoraro I, Stel G, Amstad P, Cerutti P. The defense against free radicals protects endothelial cells from hyperglycaemia-induced plasminogen activator inhibitor 1 over-production. Blood Coagul Fibrinolysis 1995; 6:133.

    Article  PubMed  CAS  Google Scholar 

  20. Trifiletti A, Barbera M, Pizzoleo MA, Lasco A, Lucifora S, Leone G, Soracie S, Pedulla M, Frisina M. Hemostatic variables in arterial hypertension. Haemostasis 1995; 25:237.

    PubMed  CAS  Google Scholar 

  21. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 25:245.

    Google Scholar 

  22. Ligthart GJ, Corberand JX, Fournier C, Galanaud P, Hijman W, Kennes B, Muller-Hermelink HK, Steimann GG. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 1984; 28:47.

    Article  PubMed  CAS  Google Scholar 

  23. Declerk PJ. Multicenter evaluation of commercially available methods for the immunological determination of plasminogen active or inhibitor-1 (PAI-1) Thromb Haemost 1993; 70:858.

    Google Scholar 

  24. Juan-Vague I, Moerman B, De Cock F, Aillaud MF, Collen D. Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. Thromb Res 1984; 33:523.

    Article  Google Scholar 

  25. Cao G, Alessio HM, Cutler RG. Oxygen-radical absorbance capacity assay for antioxidants. Free Radic Biol Med 1993; 14:303.

    Article  PubMed  CAS  Google Scholar 

  26. Testa R, Testa I, Manfrini S, Bonfigli AR, Piantanelli L, Marra M, Pieri C. Glycosylated hemoglobin and fructosamines: does their determination really reflect the glycemic control in diabetic patients? Life Sci 1996; 59:43.

    Article  PubMed  CAS  Google Scholar 

  27. Takada Y, Urano T, Watanabe I, Taminato A, Yoshimi T, Takada A. Changes in fibrinolytic parameters in male patients with type 2 (non-insulin-dependent) diabetes mellitus. Thromb Res 1993; 71:405.

    Article  PubMed  CAS  Google Scholar 

  28. Morishita E, Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Yamazaki M, Aoshima K, Hashimoto T, Matsuda T. Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus. Atherosclerosis 1996; 120:7.

    Article  PubMed  CAS  Google Scholar 

  29. Schreiner PJ, Heiss G, Tyroler HA, Morrisett JD, Davis CE, Smith R. Race and gender differences in the association of Lp(a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol 1996; 16:471.

    PubMed  CAS  Google Scholar 

  30. Gray RP, Hydkin JS, Patterson DL. Plasminogen activator inhibitor: a risk factor for myocardial infarction in diabetic patients. Br Heart J 1992; 69:228.

    Article  Google Scholar 

  31. Utermann G, Menzel HJ, Kraft HG, Duaba HC, Kemmler HG, Seitz C. Lp(a) glycoprotein phenotypes inheritance and relation to Lp(a): lipoprotein concentrations in plasma. J Clin Invest 1987; 80:458.

    Article  PubMed  CAS  Google Scholar 

  32. Sonnichsen AC, Richler WO, Schwandt P. Reduction of lipoprotein(a) by weight loss. Int J Obes 1990; 14:487.

    PubMed  CAS  Google Scholar 

  33. Kervinen K, Savolainen MJ, Kesaniemi YA. A rapid increase in lipoprotein(a) levels after ethanol withdrawal in alcoholic men. Life Sci 1991; 48:2183.

    Article  PubMed  CAS  Google Scholar 

  34. Boyer H, Gennes JL de, Truffert J, Chatellier G, Dairou F, Bruckert E. Lp(a) levels in different types of dyslipidemia in the French population. Atherosclerosis 1990; 85:61.

    Article  PubMed  CAS  Google Scholar 

  35. Juhan-Vague I, Vague P, Alessi MC, Badier C, Valadier J, Aillaud MF. Relationships between plasma insulin, triglyceride, body mass index and plasminogen activator inhibitor 1. Diabetes Metab 1987; 13:331.

    CAS  Google Scholar 

  36. Mussoni L, Mannucci L, Sirtori M, Camera M, Maderna P, Sironi L, Tremoli E. Hypertriglyceridemia and regulation of fibrinolytic activity. Artherioscler Thromb 1992; 12:19.

    CAS  Google Scholar 

  37. Medina R, Socher SH, Han JH, Friedman PA. Interleukin-1, endotoxin or tumor necrosis factor/cachectin enhance the level of plasminogen activator inhibitor messenger RNA in bovine aortic endothelial cells. Thromb Res 1989; 54:41.

    Article  PubMed  CAS  Google Scholar 

  38. Gris JC, Schved JF, Aguilar-Martinez P, Arnaud A, Sanchez N. Impact of physical training on plasminogen activator inhibitor activity in sedentary men. Fibrinolysis 1990; 4:97.

    Article  CAS  Google Scholar 

  39. Vicari AM, Viganò D’Angelo S, Testa S, Comi G, Garlardi G, Orsi E, D’Angelo A. Normal tissue plasminogen activator and plasminogen activator inhibitor activity in plasma from patients with type I diabetes mellitus. Horm Metab Res 1991; 24:516.

    Article  Google Scholar 

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Authors and Affiliations

  1. Center of Biochemistry, Department of Gerontological Research, INRCA, Via G. Birarelli,8, I-60121, Ancona, Italy

    R. Testa & A. R. Bonfigli

  2. Center of Cytology, Department of Gerontological Research, INRCA, Ancona, Italy

    C. Pieri & M. Marra

  3. Center of Demographic and Statistical Studies, INRCA, Ancona, Italy

    C. Sirolla

  4. Institute of Internal Medicine, University of Ancona, Italy

    S. Manfrini & I. Testa

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  1. R. Testa
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Testa, R., Bonfigli, A.R., Pieri, C. et al. A significant relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus without complications. Int J Clin Lab Res 28, 187–191 (1998). https://doi.org/10.1007/s005990050042

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  • DOI: https://doi.org/10.1007/s005990050042

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