Summary
Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen,d-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p<0.005,p<0.02), factor VII activity (p<0.0002,p<0.002), factor VII antigen (p<0.0001,p<0.001), protein C (p<0.003,p<0.05), and lipid peroxides (p<0.02,p<0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p<0.001) and protein S (p<0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.
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References
Morrish NJ, Stevens LK, Head J, Fuller JH, Jarrett RJ, Keen H (1990) A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) I: causes and death rates. Diabetologia 33: 538–541
Morrish NJ, Stevens LK, Head J, Fuller JH, Jarrett RJ, Keen H (1990) A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: associated risk factors. Diabetologia 33: 542–548
Fuller JH, Keen H, Jarrett RJ et al. (1979) Haemostatic variables associated with diabetes and its complications. BMJ II: 964–966
Schernthaner G, Vukovich T, Gisinger C (1991) Anomalies de l'hemostase au cours du diabete sucre. In: Flammarion Medecine Sciences-Journees de Diabetologie, Paris, France, pp 91–107
Kannel WB, D'Agostino RB, Wilson PW, Belanger AJ, Gagnon DR (1990) Diabetes, fibrinogen and risk of cardiovascular disease: the Framingham experience. Am Heart J 120: 672–676
Meade TW, Mellows S, Brozovic M et al. (1986) Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet II: 533–537
Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A, Deckert T (1987) Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors. Diabetologia 30: 144–148
Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity onset diabetes. N Engl J Med 310: 356–360
Jarrett RJ, Viberti GC, Argyropoulos A, Hill RD, Mahmud U, Murrells TJ (1984) Microalbuminurea predicts mortality in noninsulin dependent diabetes. Diabetic Med 1: 17–19
Schmitz A, Vaeth M (1988) Microalbuminurea: a major risk factor in non-insulin-dependent diabetes: a 10 year follow-up of 503 patients. Diabetic Med 5: 126–134
Mattock MB, Morrish NJ, Viberti G, Keen H, Fitzgerald AP, Jackson G (1992) Prospective study of microalbuminurea as predictor for mortality in NIDDM. Diabetes 41: 736–741
Mogensen CE, Christensen CK, Vittinghus E (1983) The stages in diabetic renal disease with emphasis on the stage of incipient diabetic nephropathy. Diabetes 32 [Suppl 2]: 64–78
Clauss A (1957) Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol Leipzig 17: 237–240
Yagi K (1987) Lipid peroxides and human diseases. Chem Phys Lipids 45: 337–351
SAS users guide (1985) SAS Institute, Cary, NC
Sandset PM, Sirnes PA, Abildgaard U (1989) Factor VII and extrinsic pathyway inhibitor in acute coronary disease. Br J Haematol 72: 391–396
Jumming L, Vilcek J (1988) Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest 61: 588–602
Collier A, Rumley A, Rumley AG et al. (1992) Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminurea. Diabetes 41: 909–913
Schmitz A, Ingerslev J (1990) Haemostatic measurements in type 2 diabetic patients with microalbuminurea. Diabetic Med 7: 521–525
Vukovich T, Schernthaner G (1986) Decreased protein C levels in patients with insulin dependent diabetes mellitus. Diabetes 35: 617–619
Schernthaner G, Vukovich T, Knöbl P, Hay U, Müller M (1989) The effect of near normoglycaemic control on plasma levels of coagulation factor VII and the anticoagulants protein C and S in insulin dependent diabetic patients. Br J Haematol 73: 356–359
Vigano S, Mannucci PM, D'Angelo A et al. (1984) Protein C antigen is not an acute phase reactant and is often high in ischemic heart disease and diabetes. Thromb Haemost 52: 263–266
Saito M, Kumabashiri I, Jokaji H et al. (1988) The levels of protein C and protein S in plasma in patients with type II diabetes mellitus. Thromb Res 52: 479–486
Oida K, Takai H, Maeda H et al. (1990) Plasma thrombomodulin concentration in diabetes mellitus. Diabetes Res Clin Pract 10: 193–196
Tanaka A, Ishii H, Hiraishi S, Kazama M, Maezawa H (1991) Increased thrombomodulin values in plasma of diabetic men with microangiopathy. Clin Chem 37: 269–272
Schwarz HP, Heeb MJ, Wence-Drake J, Griffin JH (1985) Identification and quantitation of protein S in human platelets. Blood 66: 1452–1456
Ceriello A, Giuliano D, Quatraro A, Marchi E, Barbanti M, Lefebvre P (1990) Possible role for increased C4 b-binding protein level in acquired protein S deficiency in type 1 diabetes. Diabetes 39: 447–449
Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T (1989) Features of endothelial cell dysfunction in early diabetic nephropathy. Lancet I: 461–463
Vukovich TC, Schernthaner G, Knöbl PN, Hay U (1989) The effect of near-normoglycaemic control on plasma factor VIII/von Willebrand factor and fibrin degradation products in insulin dependent diabetic patients. J Clin Endocrinol Metab 69: 84–89
Stehouwer CDA, Nauta JJP, Zeldenrust GC, Hackeng WHL, Donker AJM, den Ottolander GJH (1992) Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 340: 319–323
Stringer MD, Görög PG, Freeman A, Kakker VV (1989) Lipid peroxides and atherosclerosis. BMJ 298: 281–284
Warso MA, Lands WEM (1983) Lipid peroxidation in relation to prostacyclin and thromboxane physiology and pathophysiology. Br Med Bull 39: 277–280
Gisinger CH, Jeremy J, Speiser P, Mikhailides D, Dandonda D, Schernthaner G (1988) Effect of vitamin E treatment on platelet thromboxane A2 production in insulin dependent (type 1) diabetic patients: a double blind cross over trial. Diabetes 37: 1260–1264
Schernthaner G, Sinzinger H, Silberbauer K, Freyler H, Mühlhauser I, Kaliman J (1981) Vascular prostacyclin, platelet sensitivity to prostaglandins and platelet specific proteins in diabetes mellitus. Horm Metab Res 11: 33–43
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Knöbl, P., Schernthaner, G., Schnack, C. et al. Thrombogenic factors are related to urinary albumin excretion rate in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 1045–1050 (1993). https://doi.org/10.1007/BF02374497
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DOI: https://doi.org/10.1007/BF02374497