Activated platelets in subjects at increased risk of IDDM. DENIS Study Group. Deutsche Nikotinamid Interventionsstudie.
Activated platelets respond to activated leukocytes and endothelial cells via adhesion molecules linking inflammation and thrombosis. Platelets of recent-onset insulin-dependent diabetic (IDDM) patients have been shown to be activated independent of metabolic control. This study evaluates the levels of circulating activated platelets exposing adhesion molecules in healthy subjects at increased risk of IDDM (surface markers were: P-selectin (CD62), thrombospondin, lysosomal GP53 (CD63). From the DENIS and the ENDIT screening programmes 19 identified islet cell antibody positive (titre > or = 20 Juvenile Diabetes Foundation units) first degree relatives of IDDM patients (male/female 9/10; age 22 +/- 15 years; body mass index (BMI): 20.0 +/- 4.3 kg/m2) with clearly normal metabolism (HbA1: 6.1 +/- 0.8%; fasting blood glucose: 4.95 +/- 0.67 mmol/l) were available for this investigation. Platelet CD62 as well as thrombospondin and CD63 expression were determined by flow cytometry. We matched 50 normal volunteers for age (29 +/- 6 years), anthropometric measures (male/female 26/24; BMI: 22.3 +/- 2.8 kg/m2) and metabolic parameters (HbA1: 5.8% +/- 0.3; fasting blood glucose: 4.41 +/- 0.53 mmol/1) served as control subjects. The mean number of CD62+ platelets was increased 3.2-times in prediabetic patients: 1.94 x 2.91 (+/- 1) vs 0.60 x 1.83 (+/- 1%), p < 0.0001. Thrombospondin+ and CD63+ platelet levels were concomitantly increased (1.45 x 2.38( +/- 1)/5.97 x 2.89 (+/- 1)% vs 0.52 x 2.01 (+/-1)/1.64 x 2.26 (+/-1)%, p < 0.0001 for both comparisons). Thus, intravasal platelet activation is already present in potentially prediabetic subjects representing an antecedent, potentially pathogenic feature of IDDM.
Tschoepe
D
D
Diabetes Research Institute, Düsseldorf, Germany.
Driesch
E
E
Schwippert
B
B
Lampeter
E F
EF
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001323:Autoantibodies / Q000097:blood; D001792:Blood Platelets / Q000276:immunology; D016001:Confidence Intervals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D060149:Tetraspanin 30; D019699:Thrombospondins
D015703:Antigens, CD; D001323:Autoantibodies; C554586:CD63 protein, human; D008562:Membrane Glycoproteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D019699:Thrombospondins; C024211:islet cell antibody