Download PDF
Thromb Haemost 1994; 72(06): 979-984
DOI: 10.1055/s-0038-1648993
Original Article
Schattauer GmbH Stuttgart

Increased Levels of Soluble Adhesion Molecules in Type 2 (Non-Insulin Dependent) Diabetes mellitus Are Independent of Glycaemic Control

M Steiner
1   The University of Rostock, Institute of Clinical Chemistry and Pathobiochemistry, Rostock, Germany
,
K M Reinhardt
1   The University of Rostock, Institute of Clinical Chemistry and Pathobiochemistry, Rostock, Germany
,
B Krammer
1   The University of Rostock, Institute of Clinical Chemistry and Pathobiochemistry, Rostock, Germany
,
B Ernst
1   The University of Rostock, Institute of Clinical Chemistry and Pathobiochemistry, Rostock, Germany
,
A D Blann
2   Department of Surgery, University Hospital of South Manchester, Didsbury, Manchester, UK
› Author Affiliations
Further Information

Publication History

Received 30 May 1994

Accepted after revision 08 August 1994

Publication Date:
06 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Patients with Type 2 (non-insulin dependent) diabetes mellitus are at increased risk of thrombosis and the premature development of atherosclerosis. This may be related to damage to the endothelium (which may be the primary target tissue for the disease process) resulting from a loss of normal glycaemic metabolic control. Thus changes in endothelial cell function, such as modified release of soluble leukocyte and platelet adhesion molecules, may be important. Accordingly, E-selec-tin, von Willebrand factor (vWf), vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) were measured in serum from 60 patients and 76 controls. Raised levels of vWf (p = 0.0002), E-selectin (p <0.0001) and VC AM (p = 0.003) in patient’s samples failed to correlate with glycaemic control as assessed by levels of fructosamine and glycated haemoglobin, or with 24 h urine albumin. Levels of ICAM were not increased in our patients. Levels of the two endothelial cell products, vWf and E-selectin, failed to correlate although E-selectin correlated with low density lipoprotein cholesterol (p = 0.016). vWf correlated with VCAM (p <0.001) and hypertension (p = 0.032). We conclude that levels of soluble adhesion molecules vWf, E-selectin and VCAM are raised in Type 2 diabetes mellitus. The mechanisms for these changes appear to be independent of glycaemic control but may relate to concurrent hypertension and/or hypercholes-terolaemia.

 

  • References

  • 1 Steiner G. Diabetes and atherosclerosis. Diabetes 1981; 30 (Suppl. 02) 1-7
    PubMedSearch in Google Scholar
  • 2 Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990’s. Nature 1993; 362: 801-809
    CrossrefPubMedSearch in Google Scholar
  • 3 Blann AD, McCollum CN. Von Willebrand factor, endothelial cell damage and atherosclerosis. Eur J Vase Surg 1994; 8: 10-15
    CrossrefPubMedSearch in Google Scholar
  • 4 Greaves M, Pickering C, Knight G, Boulton AJM, Ball J, Ward JD, Preston FE. Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage. Diabetologia 1987; 30: 160-165
    CrossrefPubMedSearch in Google Scholar
  • 5 Stehouwer CDA, Nauta JJP, Zeldenrust GC, Hackeng WHL, Donker AJM, den Ottolander GJH. Urinary albumin excretion, cardiovascular disease and endothelial cell dysfunction in non-insulin dependent diabetes mellitus. Lancet 1992; 340: 319-323
    CrossrefPubMedSearch in Google Scholar
  • 6 Stehouwer CDA, Stroes ESG, Hackeng WHL, Mulder PGH, den Ottolander GJH. Von Willebrand factor and development of diabetic nephropathy in IDDM. Diabetes 1991; 40: 971-976
    CrossrefPubMedSearch in Google Scholar
  • 7 Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425-434
    CrossrefPubMedSearch in Google Scholar
  • 8 Anonymous Editorial. Atherosclerosis goes to the wall Lancet 1992; 339: 647-648
    PubMedSearch in Google Scholar
  • 9 Gearing AJH, Hemingway I, Pigott R, Hughes J, Rees AJ, Cashman SJ. Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1 and VCAM-1: Pathological significance. Annals NY Acad Sci 1992; 667: 324-331
    CrossrefPubMedSearch in Google Scholar
  • 10 Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506-512
    CrossrefPubMedSearch in Google Scholar
  • 11 Lampeter ER, Kishimoto TK, Rothlein R, Mainolfi EA, Bertrams J, Kolb H, Maretin S. Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM. Diabetes 1992; 41: 1668-1671
    CrossrefPubMedSearch in Google Scholar
  • 12 Blann AD, McCollum CN. Adverse influence of cigarette smoking on the endothelium. Thromb Haemost 1993; 70: 707-711
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Blann AD, Naqvi T, Waite MA, McCollum CN. Von Willebrand factor and endothelial cell damage in essential hypertension. J Human Hypertension 1993; 7: 107-111
    PubMedSearch in Google Scholar
  • 14 Blann AD, Bushell D, Davies A, Faragher EB, Miller JP, McCollum CN. Von Willebrand factor, the endothelium and obesity. Int J Obesity 1993; 17: 723-725
    PubMedSearch in Google Scholar
  • 15 WHO Study Group. Diabetes mellitus. Technical report series 727, 1985, WHO, Geneva, Switzerland 1-113
    PubMed
  • 16 Penttila IM, Voutilainen P, Laitinen P, Juutilainen P. Comparison of different analytical and precipitation methods for direct estimation of serum high-density lipoprotein cholesterol. Scand J Clin Lab Invest 1981; 41: 353-360
    CrossrefPubMedSearch in Google Scholar
  • 17 Friedewald WT, Levy RJ, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    PubMedSearch in Google Scholar
  • 18 Unsitupa MIJ, Niskanen LK, Siitonen O, Voutilainen E, Pyorala K. Ten year cardiovascular mortality in relation to risk factor and abnormalities in lipoprotein composition in Type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Diabetologia 1993; 36: 1175-1184
    CrossrefPubMedSearch in Google Scholar
  • 19 Fontbonne A, Eschwege E, Cambien FN, Richard JL, Ducimetiere P, Thi-bult N, Wamet JM, Claude JR, Rosselin GE. Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Diabetologia 1989; 32: 300-304
    CrossrefPubMedSearch in Google Scholar
  • 20 Sosenko JM, Kato M, Soto R, Goldberg RB. Plasma lipid levels at diagnosis in type 2 diabetic patients. Diabetic Medicine 1993; 10: 814-819
    CrossrefPubMedSearch in Google Scholar
  • 21 Blann AD, McCollum CN. Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis. Thromb Haemost 1994; 72: 151-154
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Li H, Cybulsky MI, Gimbrone MA, Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arteriosclerosis Thromb 1993; 13: 197-204
    CrossrefPubMedSearch in Google Scholar
  • 23 O’Brien K, Allen M, McDonald T, Chait A, Harlan J, Fishbein D, McCarty J, Ferguson M, Hudkins K, Benjamin C. Vascular cell adhesion molecule 1 is expressed in human coronary atherosclerotic plaques: implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 1993; 92: 945-951
    CrossrefPubMedSearch in Google Scholar
  • 24 Libby P, Li H. Vascular cell adhesion molecule-1 and smooth muscle cell activation during atherogenesis. J Clin Invest 1993; 92: 538-589
    CrossrefPubMedSearch in Google Scholar
  • 25 Richardson M, Hadock SJ, DeReske M, Cybulsky MI. Increased expression in vivo of VCAM-1 and E-Selectin by the aortic endothelium of normolipaemic and hyperlipaemic diabetic rabbits. Arteriosclerosis Thromb 1994; 14: 760-769
    CrossrefPubMedSearch in Google Scholar
  • 26 Consensus Statement of the American Diabetic Association. Role of cardiovascular risk factors in prevention and treatment of macrovascular disease in diabetes Diabetes Care 1989; 12: 573-579
    PubMedSearch in Google Scholar
  • 27 Mattock MB, Morrish NJ, Viberti G, Keen H, Fitzgerald AP, Jackson G. Prospective study of microalbuminuria as predictor of mortality in NIDDM. Diabetes 1992; 41: 736-741
    CrossrefPubMedSearch in Google Scholar
  • 28 Ruderman NB, Gupta S, Sussman I. Hyperglycaemia, diabetes and vascular disease; an overview. In: Hyperglycaemia, diabetes and vascular disease Ruderman N, Williamson J, Brownlee M. (eds) Oxford; Oxford University Press: 1992: 3-20
  • 29 Winocour PH. Microalbuminuria Worth screening for in early morning urine samples in diabetic, hypertensive and elderly patients. Br Med J 1992; 304: 1196-1197
    CrossrefPubMedSearch in Google Scholar
  • 30 Stehouwer CDA, Zellenrath P, Polak BCP, Baarsma GS, Nauta JJP, Donker AJM, den Ottolander GJH. Von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion. Diabeto-logia 1992; 35: 555-559
    CrossrefPubMedSearch in Google Scholar
  • 31 Pearson JD. Markers of endothelial perturbation and damage. Br J Rheum 1993; 32: 651-652
    CrossrefPubMedSearch in Google Scholar
  • 32 Knaap JHVD, de Boer AC, Pannebakker MAG, van Heerde W, den Ottolander GJH. The effect of diabetes regulation on platelet release, fibrinolysis and coagulation tests, before and after stimulation with DDAVP. Thromb Haemost 1985; 53: 118-121
    Thieme ConnectPubMedSearch in Google Scholar
  • 33 Colwell JA. Vascular thrombosis in type II diabetes mellitus. Diabetes 1993; 42: 8-11
    CrossrefPubMedSearch in Google Scholar
  • 34 Ceriello A. Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia 1993; 36: 1119-1125
    CrossrefPubMedSearch in Google Scholar
  • 35 Knobl P, Schemthaner G, Schnack C, Pietschmann P, Griesmacher A, Prager R, Muller M. Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin dependent) and type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 1045-1050
    CrossrefPubMedSearch in Google Scholar