Based on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.
The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.
Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).
In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.
References
1
Colwell JA.
Vascular thrombosis in type II diabetes mellitus (editorial). Diabetes 1993; 42 (01) 8-11
3
Tschoepe D,
Driesch E,
Schwippert B,
Nieuwenhuis HK,
Gries FA.
Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by near-normoglycemia. Diabetes 1995; 44: 890-894
4
Colwell JA,
Winocour PD,
Halushka PV.
Do platelets have anything to do with diabetic microvascular disease. Diabetes 1983; 32 (Suppl. 02) Suppl 14-19
5
Vukovich TC,
Schemthaner G,
Knobi PN,
Hay U.
The effect of near-normoglycemic control on plasma factor VUI/von Willebrand factor and fibrin degradation products in insulin-dependent diabetic patients. J Clin Endocrinol Metab 1989; 69 (01) 84-89
14
Kaikita K,
Ogawa H,
Yasue H,
Sakamoto T,
Suefujig H,
Sumida H.
et al
Soluble P-selectin is released into the coronary circulation after coronary spasm. Circulation 1995; 92: 1827-1830
15
Ikeda H,
Takajo Y,
Kazuya I,
Takafumi U,
Maki S,
Noda T,
Sugi K,
Imaizumi T.
Increased soluble form of P-selectin in patients with unstable angina. Circulation 1995; 92: 1693-1696
17
Wu G,
Li F,
Li P,
Ruan C.
Detection of plasma alpha-granule membrane protein GMP-140 using radiolabeled monoclonal antibodies in thrombotic disease. Haemostasis 1993; 23 (02) 121-128
19
McLeod DS,
Lefer DJ,
Merges C,
Lutty GA.
Enhanced expression of intercellular adhesion molecule-1 and P-Selectin in diabetic human retina and choroid. Am J Pathol 1995; 147 (03) 642-653
23
Knobl P,
Schemthaner G,
Schnack C,
Pietschmann P,
Griesmacher A,
Prager R,
Muller M.
Thrombogenic factors are related to uninary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36 (10) 1045-1050
24
Khawand CE,
Jamart J,
Donckier J,
Chatelain B,
Moriau M,
Buysschaert M.
Hemostasis variables in type I diabetic patients without demonstrable vascular complications. Diabetes Care 1993; 16 (08) 1137-1145
27
Ceriello A,
Giacomello R,
Stel G,
Motz E,
Taboga C,
Tonutti L,
Falleti E,
Bartoli E.
Hyperglycemia-induced thrombin formation in diabetes. The possible role of oxidative stress. Diabetes 1995; 44: 924-928
29
Johnston GI,
Bliss GA,
Newman PJ,
McEver RP.
Structure of the human gene encoding GMP-140, a member of the selectin family of adhesion receptors for leukocytes. J Biol Chem 1990; 265: 21381-21385
30
Katayama M,
Handa M,
Ambo H,
Araki Y,
Kawai Y,
Watanabe K,
Ikeda Y.
Soluble P-selectin is present in normal circulation and its plasma level is elevated in patients with thrombotic thrombocytopenic purpura and haemo-lytic uraemic syndrome. Br J Haematol 1993; 84: 702-710
33
Freedman S,
Hatchell D.
Enhanced superoxide radical production by stimulated polymorphonuclear leukocytes in a cat model of diabetes. Exp Eye Res 1992; 55: 767-773
34
Fasching P,
Rohac M,
Waldhausl W,
Soregi G,
Veitl M,
Schneider B,
Streli C,
Wagner OF.
Elevated concentrations of circulating adhesion molecules and their association with late diabetic complications in insulin-dependent and non-insulin-dependent diabetes mellitus. submitted
35
Lampeter ER,
Kishimoto TK,
Rothlein R,
Mainolfi EA,
Bertrams J,
Kolb H,
Martin S.
Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM. Diabetes 1992; 41 (12) 1668-1671
36
Steiner M,
Reinhardt KM,
Krammer B,
Ernst B,
Blann AD.
Increased levels of soluble adhesion molecules in type 2 (non-insulin dependent) diabetes mellitus are independent of glycaemic control. Thromb Haemost 1994; 72 (06) 679-684
37
Celi A,
Pellegrini G,
Lorenzet R,
Blasi AD,
Ready N,
Furie BC,
Furie B.
P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci 1994; 8767-8771
