Summary
The biological activity of thrombin and coagulation factor Xa was assessed in 62 insulin-dependent diabetic patients. A group of non-diabetic subjects of comparable age and urinary albumin excretion rate (<30 mg/24 h) served as control subjects (group 1,n=14). The patients were divided into three groups according to urinary albumin excretion rate. In group 2, albumin excretion rate was less than 30 mg/24 h (n=17), in group 3 albumin excretion rate was in the range 30–300 mg/24 h (n=20) and in group 4 albumin excretion rate was greater than 300 mg/24 h (n=25). Compared to non-diabetic control subjects an increase in the biological activity of factor Xa was observed in all groups of diabetic patients (prothrombin fragment 1+2 levels were 1.14±0.38 nmol/l in group 2,p<0.005; 1.06±0.45 nmol/l in group 3,p<0.05 and 1.03±0.31 nmol/l in group 4,p<0.05 vs 0.75±0.34 nmol/l in group 1). No difference in the level of antithrombin III was seen between the groups. We reconfirmed the presence of intimal dysfunction in diabetic nephropathy demonstrated by elevated transcapillary escape rate of albumin in group 4 compared with group 2 (8.9±2.0% vs 7.0±1.9%,p<0.05). An overall positive correlation between transcapillary escape rate and prothrombin fragment 1+2 was found (r=0.36,p<0.005). However, in the groups with elevated albumin excretion rate such a correlation was not significant (group 3:r=0.15,p=0.54; group 4:r=0.03,p=0.86) while it was sustained in the groups with albumin excretion rate of less than 300 mg/24 h (group 1:r=0.61,p<0.05; group 2:r=0.64,p<0.05). In conclusion, IDDM patients had elevated biological activity of factor Xa, demonstrated by elevated levels of prothrombin fragment 1+2. This increment could not be explained by a deficiency of antithrombin III. [Diabetologia (1995) 38: 73–78]
Similar content being viewed by others
Abbreviations
- IDDM:
-
Insulin-dependent diabetes mellitus
- TER:
-
transcapillary of albumin
- (vWf:Ag):
-
von Willebrond Factor
- TAT:
-
thrombin-antithrombin III complexes
References
Borch-Johnsen K, Kreiner S (1987) Proteinuria — a predictor of cardiovascular mortality in insulin-dependent diabetes mellitus. BMJ 294: 1651–1654
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
Jensen T, Stender S, Deckert T (1988) Abnormalities in plasma concentrations of lipoproteins and fibrinogen in type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion. Diabetologia 31: 142–145
Lipid Research Clinics Program (1984) The lipid Research Clinics Coronary Primary Prevention Trial Results. JAMA 251: 351–374
Deckert T, Feldt-Rasmussen B, Djurup R, Deckert M (1988) Glomerular size and charge selectivity in type 1 (insulin-dependent) diabetes mellitus. Kidney Int 33: 100–106
Deckert T, Feldt-Rasmussen B, Djurup R, Deckert M (1987) Glomerular size and charge selectivity in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 513A (Abstract)
Deckert T, Kofoed-Enevoldsen A, Vidal P, Nørgaard K, Andreasen HB, Feldt-Rasmussen B (1993) Size- and charge selectivity of glomerular filtration in type 1 (insulin-dependent) diabetic patients with and without albuminuria. Diabetologia 36: 244–251
Klein DJ, Oegema TR, Brown DM (1989) Release of glomerular heparan 35-SO4 proteoglycan by heparin from glomeruli of streptozotocin-induced diabetic rats. Diabetes 38: 130–139
Kanwar YS, Rosenzweig LJ, Linker A, Jakubowski ML (1983) Decreased de novo synthesis of glomerular proteoglycans in diabetes. Proc Natl Acad Sci USA 80: 2272–2275
Rorbach R (1986) Reduced content and abnormal distribution of anionic sites (acid proteoglycans) in the glomerular basement membrane. Virchows Arch B Cell Pathol 51: 127–135
Ledbetter S, Copeland EJ, Noonan D, Vogeli G, Hassell J (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthetase inhibition. Diabetes 39: 196–203
Kanwar YS, Linker A, Farquhar MG (1980) Increased permeability of the glomerular membrane to ferritin after removal of glycosaminoglycans (heparan sulphate) by enzyme digestion. J Cell Biol 86: 688–693
Bourin M-C, Lindahl U (1993) Glycosaminoglycans and the regulation of blood coagulation. Biochem J 289: 313–330
Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32: 219–226
Parving H-H, Rasmussen SM (1973) Transcapillary escape rate of albumin and plasma volume in short- and longterm juvenile diabetics. Scand J Clin Lab Invest 32: 81–87
Bröchner-Mortensen J (1972) A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest 30: 271–274
Svendsen PA, Christiansen JS, Søegaard U, Welinder BS, Nerup J (1980) Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentrations. Diabetologia 19: 130–136
Feldt-Rasmussen B, Dinesen B, Deckert M (1985) Enzyme immunoassay: an improved determination of urinary albumin in diabetics with incipient nephropathy. Scand J Clin Lab Invest 45: 539–544
Pelzer H, Schwarz A, Stüber W (1991) Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemostas 65: 153–159
Soria J, Soria C, Ryckewaert JJ (1980) A solid phase immuno enzymological assay for the measurement of human fibrinopeptide A. Thromb Res 20: 425–435
Gram J, Jespersen J (1989) Increased concentrations of heparin cofactor II in diabetic patients, and possible effects on thrombin inhibition assay of antithrombin III. Clin Chem 35: 52–55
Ingerslev J (1987) A sensitive ELISA for von Willebrand factor (vW:Ag). Scand J Clin Lab Invest 47: 143–149
Blombäck B, Blombäck M (1956) Preparation of human fibrinogen fraction 1–2. Arkiv Kemi 10: 415–443
Pelzer H, Schwartz A, Heimburger N (1988) Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemostas 59: 101–106
Bauer KA, Goodman TL, Kass BL, Rosenberg RD (1985) Elevated factor Xa activity in the blood of asymptomatic patients with congenital antithrombin deficiency. J Clin Invest 76: 826–836
Rosove MH, Harrison JL, Frank JL, Harwig SSL (1984) Plasma β-thromboglobulin, platelet factor 4, fibrinopeptide A, and other hemostatic functions during improved, short-term glycemic control in diabetes mellitus. Diabetes Care 7: 174–179
Haaber AB, Deckert M, Stender S, Jensen T (1993) Increased urinary loss of high density lipoproteins in albuminuric insulin-dependent diabetic patients. Scand J Clin Lab Invest 53: 191–196
Gruden G, Cavallo-Perin P, Bazzan M, Stella S, Bruna A, Pagano G (1993) Haemostatic alterations in microalbuminuric insulin-dependent diabetic patients. Diabetologia 36 [Suppl 1]: A215 (Abstract)
Ceriello A, Giacomello R, Colatutto A, Taboga C, Gonano F (1992) Increased prothrombin fragment 1+2 in type 1 diabetic patients. Haemostasis 22: 50–51
Ceriello A (1993) Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia 36: 1119–1125
Rohrbach DH, Hassel JR, Kleinman HK, Martin GR (1982) Alterations in the basement membrane (heparan sulphate) proteoglycans in diabetic mice. Diabetes 31: 185–188
Parthasarathy N, Spiro RG (1982) Effect of diabetes on the glycosaminoglycan component of the human glomerular basement membrane. Diabetes 31: 738–741
Feldt-Rasmussen B (1986) Increased transcapillary escape rate of albumin in type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 29: 282–286
Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T (1989) Features of endothelial dysfunction in early diabetic nephropathy. Lancet i: 461–463
Jensen T (1989) Increased plasma concentration of von Willebrand factor in insulin dependent diabetics with incipient nephropathy. BMJ 298: 27–28
Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD (1987) Aging-associated changes in indices of thrombin generation and protein C activation in humans. J Clin Invest 80: 1527–1534
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Myrup, B., Rossing, P., Jensen, T. et al. Procoagulant activity and intimal dysfunction in IDDM. Diabetologia 38, 73–78 (1995). https://doi.org/10.1007/BF02369355
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02369355