Plasma β-Thromboglobulin, Platelet Factor 4, Fibrinopeptide A, and Other Hemostatic Functions During Improved, Short-Term Glycemic Control in Diabetes Mellitus

Abstract

To determine the effect of improved, short-term glycemic control on various functions of hemostasis in insulin-dependent diabetes, we measured changes in plasma fibrinogen, fibrinopeptide A (FPA), functional antithrombin III (AT-III), factor VIII:ristocetin cofactor (VIIIRCoF), beta-thromboglobulin (BTG), platelet factor 4 (PF4), and platelet aggregation responses to ADP and collagen in 12 patients with low or undetectable stimulated (postprandial) serum C-peptide levels during 4–8 wk (median, 6 wk) of treatment with constant subcutaneous insulin infusion. Mean plasma fibrinogen, FPA, AT-III, VIIIRCoF , and BTG at baseline were elevated compared with normal. Three patients had heightened platelet responses to ADP that did not correlate to other indicators of a hypercoagulable state; the affected patients, in fact, had significantly lower plasma BTG (25.5 ± 5.3 [SEM] versus 44.6 ± 4.6 ng/ml, P < 0.05) and FPA (1.1 ± 0.1 versus 2.5 ± 0.5 ng/ml, P < 0.05) than the remaining patients. Patients with clinically evident vascular disease had higher baseline plasma BTG and FPA than those without vascular disease (44.6 ± 5.4 versus 30.2 ± 4.6, and 2.6 ± 0.6 versus 1.3 ± 0.2 ng/ml, P < 0.05, respectively). During treatment, all patients had declining blood glucose (200 ± 18 to 102 ± 5 mg/dl, P < 0.001) and HbA1 (11.8 ± 0.6 to 10.2 ± 0.4%, P < 0.005). No statistically significant changes in hemostaticfunctions were noted. During treatment, one patient had an acute myocardial infarction. It appears that short-term glycemic control alone in insulin-dependent diabetes does not exert a remarkable ameliorative effect on some aspects of hemostatic hyperfunction as defined by currently available, sensitive laboratory tests. It remains to be determined whether excellent long-range control, taking into consideration the extent of pre-existing vascular disease, might be more successful.