Enhanced Anticoagulant Response to Activated Protein C in Patients With IDDM

Anticoagulant response to activated protein C (APC) was studied in 40 healthy subjects and 67 patients with insulin-dependent diabetes mellitus (IDDM) using a modified activated thromboplastin time assay. Results are expressed in terms of the APC sensitivity ratio (APC SR). In addition, plasma levels of protein C, total and free protein S (PS), coagulation factors V and VIII, and prothrombin fragment 1+2 (F1+2) were measured. Patients with IDDM and a urinary albumin excretion rate (UAER) <30 mg/24 h showed a median APC SR of 2.5 (interquartile range 2.3–2.9). In patients with a UAER between 30 and 300 mg/24 h, the median APC SR was 2.7 (2.7–2.9). Both values were significantly greater than the median APC SR of 2.1 (2.0–2.5) observed in healthy control subjects (P < 0.001). Also, the percentage of subjects with an APC SR ≤2.0 was markedly smaller in both patient groups. Factor V and VIII levels were not significantly different between IDDM patients and healthy subjects. Grouping of IDDM patients according to the APC SR revealed significantly enhanced levels of total PS (P < 0.05) and factor VIII (P < 0.01) in patients with a poor anticoagulant response to APC (APC SR ≤2.0) compared with those with an APC SR >2.7. The negative correlation of the APC SR in diabetic patients with both coagulation and anticoagulation factors indicates a complex role of this parameter in regulating the coagulation system in IDDM.