Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients.
Patients with diabetes mellitus manifest increased in vitro platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12-14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 +/- 15, before treatment, to 107 +/- 6 mg/dl on the final day (P less than 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05). The reduction in platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c greater than 12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P less than 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly in patients with HbA1c greater than 12% (2.8 +/- 1.3 versus 1.2 +/- 0.6 microM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007332:Insulin Infusion Systems; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D001786:Blood Glucose; D007328:Insulin; D008074:Lipoproteins; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate