ACTIVATED PLATELETS IN SUBJECTS AT INCREASED RISK OF IDDM

Activated platelets respond to activated leukocytes and endothelial ce lls via adhesion molecules linking inflammation and thrombosis. Platel ets of recent-onset insulin-dependent diabetic (IDDM) patients have be en shown to be activated independent of metabolic control. This study evaluates the levels of circulating activated platelets exposing adhes ion molecules in healthy subjects at increased risk of IDDM (surface m arkers were: P-selectin (CD62), thrombospondin, lysosomal GP53 (CD63)) . From the DENIS and the ENDIT screening programmes 19 identified isle t cell antibody positive (titre greater than or equal to 20 Juvenile D iabetes Foundation units) first degree relatives of IDDM patients (mal e/female 9/10; age 22 +/- 15 years; body mass index (BMI): 20.0 +/- 4. 3 kg/m(2)) with clearly normal metabolism (HbA(1): 6.1 +/- 0.8%; lasti ng blood glucose: 4.95 +/- 0.67 mmol/l) were available for this invest igation. Platelet CD62 as well as thrombospondin and CD63 expression w ere 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/m(2)) and metabolic parameters (HbA(1): 5.8% +/- 0.3; fasting blood glucose: 4.41 +/- 0.53 mmol/l) served as control subjec ts. The mean number of CD62(+) platelets was increased 3.2-times in pr ediabetic patients: 1.94 x 2.91(+/-1) vs 0.60 x 1.83(+/-1)%, p < 0.000 1. Thrombospondin(+) and CD63(+) platelet levels were concomitantly in creased (1.45 x 2.38(+/-1)/5.97 x 2.89(+/-1)% vs 0.52 x 2.01(+/-1)/1.6 4 x 2.26(+/-1)%, p < 0.0001 for both comparisons). Thus, intravasal pl atelet activation is already present in potentially prediabetic subjec ts representing an antecedent, potentially pathogenic feature of IDDM.