Platelet Function During Continuous Insulin Infusion Treatment in Insulin-dependent Diabetic Patients

Patients with diabetes mellitus manifest increased in vitro platelet aggregation andincreased 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 < 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 ± 28ng iTXB₂/ml/ 5 × 10⁵ platelets; P < 0.05). The reductionin platelet iTXB₂ synthesis (15 and 30 s) was greater in poorly controlled patients (HbA_1c>12%; N = 8), and for all patients the decrease in iTXB₂ (15 and 30 s) was correlated with the prestudy HbA_1c level (15 s: r = 0.6; P < 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 inpatients with HbA_1c 12% (2.8 ± 1.3 versus 1.2 ± 0.6 μM; P < 0.01). Other factors that were associated in this study with platelet aggregation responses were plasma lipoprotein levels and microvascular disease. In all patients before treatment, the ED₅₀ for AA was inversely correlated with the LDL-cholesterol level(r = 0.57; P < 0.01). Although platelet aggregation did not improve during the period of intensive treatment, when the relations of microvascular disease and glycemic control to platelet aggregation were analyzed together in all patients, the ED50 for AA was greatest (P < 0.02) in thosepatients without microvascular disease and HbA_1c <12%, indicating less platelet aggregability.

Thus, a brief period of CSII treatment reduced AA-stimulated platelet iTXB₂ generation; however, the effects of this treatment on platelet aggregation appear to be complex and other extraplatelet factors also seem to influence the aggregation response.