Elevated Concentrations of Soluble Adhesion Molecules and Large Platelets in Diabetic Patients: Are They Markers of Vascular Disease and Diabetic Nephropathy?
Free accessResearch articleFirst published online October, 2007
Elevated Concentrations of Soluble Adhesion Molecules and Large Platelets in Diabetic Patients: Are They Markers of Vascular Disease and Diabetic Nephropathy?
P-selectin, E-selectin, and mean platelet volume are markers associated with platelet reactivity that have been demonstrated to be increased in diabetes. We were particularly interested to see if there was a difference in mean platelet volume and selectins between diabetics and nondiabetics, and in diabetics with and without nephropathy, and whether there was a correlation between mean platelet volume and selectins. One hundred and fourteen diabetic patients and 31 healthy controls were investigated. Plasma levels of P-selectin and E-selectin were higher in the diabetic group than in controls (P = .001 and P = .007, respectively) and in diabetic patients with proteinuria than in patients without proteinuria (P = .002 and P = .004, respectively). Protein excretion was lower in patients with low mean platelet volume values (P = .004). In conclusion, elevated platelet volume and high selectin values may play a role in the development of vasculopathies and complications in diabetes mellitus. Further studies are needed to prove these results.
Colwell JAVascular thrombosis in type II diabetes mellitus. Diabetes . 1993;42:8-11.
2.
Ruggenenti P. , Remuzzi G.The diagnosis of renal involvement in non-insulin-dependent diabetes mellitus. Curr Opin Nephrol Hypertens. 1997;6:141-145.
3.
UK Prospective Diabetes Study. IX. Relationships of urinary albumin and N-acetylglucosaminidase to glycaemia and hypertension at diagnosis of type 2 diabetes mellitus and after 3 months' diet therapy. Diabetologia.1993 ;36:835-842.
4.
Ritz E., Orth SRNephropathy in patients with type 2 diabetes mellitus. N Engl J Med.1999;341:1127-1133.
5.
Tschoepe D., Roesen P., Eser J., et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost.1991;17 :433-438.
6.
Tschoepe D., Driesch E., Schwippert B., et al. Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by nearnormoglycemia. Diabetes. 1995;44:890-894.
7.
Colwell JA, Winocour PD, Halushka PV, et al. Do platelets have anything to do with diabetic microvascular disease?Diabetes. 1983;32:14-19.
8.
Vukovich TC, Schernthaner G., Knobi PN, et al. The effect of near-normoglycemic control on plasma factor VIII/von Willebrand factor and fibrin degradation products in insulin-dependent diabetic patients. J Clin Endocrinol Metab.1989;69:84-89.
9.
Fasching P., Veilt M., Rohac M., et al. Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab.1996;8:4313-4317.
10.
Jude EB, Abbott CA, Andersen S., et al. The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy. Diabetologia. 1998 ;41:330-336.
11.
Gearing Ajh , Hemingway I., Pigott R., et al. Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1, and VCAM-1: pathologic significance. Ann NY Acad Sci.1992; 667:324-331.
12.
Fasching P., Waldhausl W., Wagner OFElevated circulating adhesion molecules in NIDDM-potential mediators in diabetic microangiopathy. Diabetologia. 1996;39:1242-1244.
13.
Schmidt AM, Crandall J., Hori O., et al. Elevated plasma levels of vascular cell adhesion molecule-1 in diabetic patients with microalbuminuria: a marker of vascular dysfunction and progressive vascular disease. Br J Haematol.1996;92:747-750.
14.
Steiner M., Reinhardt KM, Krammer B., et al. Increased levels of soluble adhesion molecules are independent of glycaemic control. Thromb Haemost.1994 ;72:979-984.
15.
Cominacini L. , Pasini AF, Garbin U., et al. Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control. Diabetologia. 1995;38: 1122-1124.
16.
Lampeter ER , Kishimoto TK, Rothlein R., et al. Elevated levels of circulating adhesion molecules in IDDM and in subjects at risk for IDDM . Diabetes . 1992;4:1668-1672.
17.
Aliberti G. , D'Erasmo E., Vecci E., et al. Platelet parameters in aged non insulin dependent diabetics. Arch Gerontol Geriatr.1991;12:255-258.
18.
Erikson U., Ewald U., Tuvemo T.Increased platelet volume in manifest diabetic rats. Ups J Med Sci.1983;88: 17-23.
19.
Rao AK, Goldberg RE, Walsh PNPlatelet coagulant activities in diabetes mellitus. Evidence for relationship between platelet coagulant hyperactivity and platelet volume. J Lab Clin Med.1984;103:82-92.
20.
Cagliero E. , Porta M., Cousins S., et al. Increased platelet volume in diabetic retinopathy. Haemostasis.1982;12: 293-299.
21.
Tschoepe D. , Roesen P., Eser J., et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Haemost.1991;17:433-438.
22.
Porta M., Peters AM, Cousins SA, et al. A study of platelet-relevant parameters in patients with diabetic microangiopathy. Diabetologia. 1983;25:21-25.
23.
Bennett PHThe diagnosis of diabetes: new international classification and diagnostic criteria. Annu Rev Med.1983;34:295-309.
24.
Kroc Collaborative Study Group. Blood glucose control and the evolution of diabetic retinopathy and albuminuria: a preliminary multicenter trial. N Engl J Med.1984;311:365-372.
25.
Lauritzen T. , Frost-Larsen K., Larsen H-W., et al. Two-year experience with continuous subcutaneous insulin infusion in relation to retinopathy and neuropathy. Diabetes. 1985;34:74-79.
26.
Zhao Y., He Y., Shen W., et al. Plasma P-selectin measurement using immunoassay method and its clinical significance. JExp Haematol. 1997 ;5:426-428.
27.
Ruderman NB , Grupta S., Susman I.Hyperglycemia, diabetes and vascular disease: an overview. In: Ruderman NB, Williamson J., Brownless M., eds. Hyperglycemia , Diabetes and Vascular Disease.New York : Oxford University Press;1992 :3-20.
28.
Nathan DMLong-term complications of diabetes mellitus. N Engl J Med.1993;328:1676-1685.
29.
Haffner SM, Lehto S., Ronnemaa T., et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction . N Engl J Med.1998;339:229-234.
30.
Brownlee M.Biochemistry and molecular cell biology of diabetic complications. Nature.2001;414:813-820.
31.
Fuller JH, Shipley MJ, Rose G., et al. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: The Whitehall Study. BMJ.1983;287:867-870.
32.
Strano A., Davi G., Patrono C.In vivo platelet activation in diabetes mellitus. Semin Thromb Haemost.1991;17:422-430.
33.
Carter AM, Grant PJVascular homeostasis, adhesion molecules, and macrovascular disease in non-insulin dependent diabetes mellitus. Diabet Med.1997 ;14:423-432.
34.
Blann AD, Lip Gyh.Endothelial integrity, soluble adhesion molecules and platelet markers in type 1 diabetes mellitus. Diabet Med.1998 ;15:634-642.
Jude EB, Abbott CA, Young MJ, et al. The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy. Diabetologia. 1998 ;41:330-336.
37.
McLeod DS, Lefer DJ, Merges C., et al. Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol.1995;147:642-665.
38.
Hirata K., Shikata K., Matsuda M., et al. Increased expression of selectins in kidneys of patients with diabetic nephropathy. Diabetologia. 1998;41:185-192.
39.
Martin JF, Trowbridge EA, Salmon G., et al. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res.1983;32: 443-460.
40.
Martin JF, Bath Pmw, Burr MLInfluence of platelet size on outcome after myocardial infarction. Lancet. 1991;338: 1409-1411.
41.
D'Erasmo E. , Aliberti G., Celi FS, et al. Platelet count, mean platelet volume and their relation to prognosis in cerebral infarction . J Intern Med.1990;227:11-14.
42.
Halushka PV , Lurie D., Colwell JAIncreased synthesis of prostaglandin-E-like material by platelets from patients with diabetes mellitus. N Engl J Med.1977;297:1306-1310.
43.
Heath H., Bridgen WD, Canecer JV, et al. Platelet adhesiveness and aggregation in relation to diabetic retinopathy. Diabetologia. 1971;7:308-315.
44.
Vicari AM, Macagni A.Primary platelet activation in recent onset type 1 diabetes mellitus . Scand J Clin Lab Invest.1990;50:429-432.
45.
Martny CN, Matthews DM, Popp-Snijders C., et al. Effects of sorbinil treatment on erythrocytes and platelets of persons with diabetes. Diabetes Care. 1986 ;9:36-39.
Steiner M., Reinhardt KM, Krammer B., et al. Increased levels of soluble adhesion molecules are independent of glycaemic control. Thromb Haemost.1994 ;72:979-984.
48.
Cominacini L. , Pasini AF, Garbin U., et al. Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control. Diabetologia. 1995;38: 1122-1124.
49.
Nomura S., Kagawa H., Ozaki Y., et al. Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies. Thromb Res.1999;95:205-213.
50.
Rozanski A. , Blumenthal JA, Kaplan J.Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation . 1999;99: 2192-2217.
