The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects

Marlien Pieters; Namukolo Covic; Du Toit Loots; Francois H. van der Westhuizen; Danie G. van Zyl; Paul Rheeder; Johann C. Jerling; John W. Weisel

doi:10.1160/TH06-07-0390

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 96(05): 623-629
DOI: 10.1160/TH06-07-0390

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects

Autor*innen

Marlien Pieters

¹Department of Nutrition, North-West University, Potchefstroom, South Africa
Namukolo Covic

¹Department of Nutrition, North-West University, Potchefstroom, South Africa
Du Toit Loots

¹Department of Nutrition, North-West University, Potchefstroom, South Africa
Francois H. van der Westhuizen

²School of Biochemistry, North-West University, Potchefstroom, South Africa
Danie G. van Zyl

³Department of Internal Medicine, University of Pretoria, South Africa
Paul Rheeder

⁴Division of Clinical Epidemiology, University of Pretoria, Pretoria, South Africa
Johann C. Jerling

¹Department of Nutrition, North-West University, Potchefstroom, South Africa
John W. Weisel

⁵Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Abstract

Summary

Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures. The subjects were then treated with insulin until blood glucose control was achieved before end blood samples were taken. Twenty age- and BMI-matched non-diabetic subjects were included as a reference group. The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs. 3.89 mol glucose / mol fibrinogen;p < 0.001).This was significantly reduced during the intervention (7.84 to 5.24 mol glucose / mol fibrinogen; p< 0.0002) in the diabetic group. Both groups had high mean fibrinogen concentrations (4.25 and 4.02 g/l, diabetic and non-diabetic subjects respectively). There was no difference in fibrinogen concentration, porosity, compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline, nor were there any changes during the intervention despite the reduced fibrinogen glycation. Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control. Improved glycaemic control resulted in decreased fibrinogen glycation but not fibrinogen concentration. It seems as though porosity, compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model.

Keywords

Diabetes - glycation - fibrinogen - fibrin network structure - glucose control

Volltext

Referenzen

References
1 Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. J Am Med Assoc 1979; 241: 2035-8.
2 Dunn EJ, Ariens RA. Fibrinogen and fibrin clot structure in diabetes. Herz 2004; 29: 470-9.
3 Danesh J, Lewington S, Thompson SG. et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. J Am Med Assoc 2005; 294: 1799-809.
4 Koenig W. Fibrin(ogen) in cardiovascular disease: an update. Thromb Haemost 2003; 89: 601-9.
5 Collet JP, Park D, Lesty C. et al. Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy. Arterioscler Thromb Vasc Biol 2000; 20: 1354-1361.
6 Dunn EJ, Ariens RA, Grant PJ. The influence of type 2 diabetes on fibrin structure and function. Diabetologia 2005; 48: 1198-206.
7 Nair CH, Azhar A, Wilson JD. et al. Studies on fibrin network structure in human plasma. Part II--Clinical application: diabetes and antidiabetic drugs. Thromb Res 1991; 64: 477-85.
8 Jorneskog G, Egberg N, Fagrell B. et al. Altered properties of the fibrin gel structure in patients with IDDM. Diabetologia 1996; 39: 1519-23.
9 Lutjens A, te Velde AA, vd Veen EA. et al. Glycosylation of human fibrinogen in vivo . Diabetologia 1985; 28: 87-9.
10 Hammer MR, John PN, Flynn MD. et al. Glycated fibrinogen: a new index of short-term diabetic control. Ann Clin Biochem 1989; 26: 58-62.
11 Ardawi MS, Nasrat HN, Mira SA. et al. Comparison of glycosylated fibrinogen, albumin, and haemoglobin as indices of blood glucose control in diabetic patients. Diabet Med 1990; 07: 819-24.
12 Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation reduces the susceptibility of fibrin to degradation by plasmin. Diabetes 1983; 32: 680-4.
13 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.
14 Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G. et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402-10.
15 Takebe M, Soe G, Kohno I. et al. Calcium ion-dependent monoclonal antibody against human fibrinogen: preparation, characterization, and application to fibrinogen purification. Thromb Haemost 1995; 73: 662-7.
16 Blomback B, Carlsson K, Fatah K. et al. Fibrin in human plasma: gel architectures governed by rate and nature of fibrinogen activation. Thromb Res 1994; 75: 521-38.
17 Fatah K, Hamsten A, Blomback B. et al. Fibrin gel network characteristics and coronary heart disease: relations to plasma fibrinogen concentration, acute phase protein, serum lipoproteins and coronary atherosclerosis. Thromb Haemost 1992; 68: 130-5.
18 Dhall TZ, Bryce WA, Dhall DP. Effects of dextran on the molecular structure and tensile behaviour of human fibrin. Thromb Haemost 1976; 35: 737-45.
19 Ford I, Singh TP, Kitchen S. et al. Activation of coagulation in diabetes mellitus in relation to the presence of vascular complications. Diabet Med 1991; 08: 322-9.
20 Festa A, D’Agostino Jr. R, Mykkanen L. et al. Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler Thromb Vasc Biol 1999; 19: 562-8.
21 Donders SH, Lustermans FA, van Wersch JW. Glycometabolic control, lipids, and coagulation parameters in patients with non-insulin-dependent diabetes mellitus. Int J Clin Lab Res 1993; 23: 155-9.
22 Avellone G, Di G V, Cordova R. et al. Blood coagulation and fibrinolysis in obese NIDDM patients. Diabetes Res 1994; 25: 85-92.
23 Asakawa H, Tokunaga K, Kawakami F. Elevation of fibrinogen and thrombin-antithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy. J Diabetes Complications 2000; 14: 121-6.
24 Jerling JC, Vorster HH, Oosthuizen W. et al. Differences in plasminogen activator inhibitor 1 activity between blacks and whites may be diet related. Haemostasis 1994; 24: 364-8.
25 Folsom AR, Wu KK, Conlan MG. et al. Distributions of hemostatic variables in blacks and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) Study. Ethn Dis 1992; 02: 35-46.
26 Kannel WB, D’Agostino RB, Wilson PW. et al. Diabetes, fibrinogen, and risk of cardiovascular disease: the Framingham experience. Am Heart J 1990; 120: 672-6.
27 Ganda OP, Arkin CF. Hyperfibrinogenemia. An important risk factor for vascular complications in diabetes. Diabetes Care 1992; 15: 1245-50.
28 Missov RM, Stolk RP, van der Bom JG. et al. Plasma fibrinogen in NIDDM: the Rotterdam study. Diabetes Care 1996; 19: 157-9.
29 Jorneskog G, Hansson LO, Wallen NH. et al. Increased plasmafibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusion. J Thromb Haemost 2003; 01: 1195-201.
30 Ryan EA, Mockros LF, Weisel JW. et al. Structural origins of fibrin clot rheology. Biophys J 1999; 77: 2813-26.
31 Lutjens A, Jonkhoff-Slok TW, Sandkuijl C. et al. Polymerisation and crosslinking of fibrin monomers in diabetes mellitus. Diabetologia 1988; 31: 825-30.
32 Ney KA, Pasqua JJ, Colley KJ. et al. In vitro preparation of nonenzymatically glucosylated human transferrin, alpha 2-macroglobulin, and fibrinogen with preservation of function. Diabetes 1985; 34: 462-70.
33 Austin GE, Mullins RH, Morin LG. Non-enzymic glycation of individual plasma proteins in normoglycemic and hyperglycemic patients. Clin Chem 1987; 33: 2220-4.