fibrinopeptide-a and Diabetes-Mellitus

Topics: Adult; Aged; Diabetes Mellitus; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Protein C

The aim of this study was to evaluate the balance between thrombin and plasmin activity in a group of 79 diabetic patients (IDDM and NIDDM). For this purpose we determined fibrinopeptide A (FPA) and B beta 15-42, specific products of thrombin and plasmin activity. Moreover we investigated the behaviour of antithrombin III and alpha 2 antiplasmin, important inhibitors of blood coagulation and fibrinolysis. Results show an increase both in FPA and B beta 15-42 in IDDM and NIDDM patients when compared to healthy controls. However the ratio between B beta 15-42 and FPA was lower than in controls indicating an imbalance between thrombin and plasmin activity. Antithrombin III levels were not different from the controls and no correlation was found with Hb A1c. alpha 2 antiplasmin was found to be higher in IDDM when compared both with NIDDM and controls. A non linear correlation was found between Hb A1c and alpha 2 AP in both diabetic groups. We conclude that the imbalance between thrombin and plasmin activity may have a role in determining fibrin deposition. These subclinical abnormalities, unrelated to vascular complications and duration of the disease, may progressively contribute to the development of the vascular complications in diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-2-Antiplasmin; alpha-Macroglobulins; Antithrombin III; Blood Coagulation; Child; Diabetes Mellitus; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Peptide Fragments; Radioimmunoassay; Thrombin

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.

Topics: beta-Thromboglobulin; Blood Coagulation; Cold Temperature; Diabetes Complications; Diabetes Mellitus; Fibrinopeptide A; Humans; Platelet Aggregation; Stress, Physiological

Abnormalities of haemostasis are common in diabetes mellitus. As indicators of fibrinolysis and coagulation, plasmin and thrombin activity were assessed by assay of the fibrinogen peptide derivatives B beta 15-42 and fibrinopeptide A respectively in 60 diabetic patients and 50 control subjects in a cross-sectional study. Glycosylated haemoglobin (HbA1) correlated with B beta 15-42 (r = -0.26, p less than 0.05) and fibrinopeptide A (r = 0.30, p less than 0.05) in the diabetic patients suggesting that poor glycaemic control (i.e. high HbA1 levels) was associated with depressed plasmin and enhanced thrombin activity. Compared to controls, fibrinopeptide A levels were increased in diabetics (p less than 0.001) irrespective of sex or type of diabetes. B beta 15-42 levels were normal in diabetic females but increased in diabetic men (p less than 0.001) possibly secondary to the activation of coagulation. These results suggest that in diabetes mellitus activation of coagulation is the dominant haemostatic abnormality and that better glycaemic control could influence in-vivo plasmin and thrombin activity favourably.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Glycated Hemoglobin; Hemostasis; Humans; Male; Middle Aged; Peptide Fragments; Thrombin

Plasma fibrinopeptide A (FPA) concentration, as a measure of thrombin activity, was determined during an insulin tolerance test in 17 non-obese diabetics. FPA was measured by a modification of the Nossel method. Administration of insulin significantly lowered plasma glucose, accompanied by a significant increase in FPA from 0.9 +/- 0.1 ng/ml to 4.3 +/- 1.6 ng/ml (P less than 0.05) as well as a significant increase in circulating levels of epinephrine and growth hormone. The magnitude of the peak in epinephrine levels correlated well with both the rate of decline of plasma glucose and the magnitude of the peak of FPA. In addition, the FPA increment was suppressed by treatment with heparin. These results indicate that insulin-induced hypoglycemia or a rapid fall in plasma glucose is associated with enhanced thrombin generation and fibrin formation, which may be considered as a contributory factor to the development of diabetic microangiopathy through a hypercoagulable state.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus; Epinephrine; Female; Fibrinogen; Fibrinopeptide A; Growth Hormone; Humans; Insulin; Kinetics; Male; Middle Aged; Norepinephrine

Topics: Adult; Aged; Diabetes Complications; Diabetes Mellitus; Diabetic Retinopathy; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged

Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ between type I and type II diabetic subjects. Comparison of plasma FPA with blood glucose and hemoglobin A1 (HbA1) indicated that elevation of FPA is rapidly reversible and intermittent during hypo- and hyperglycemia. Although elevated plasma FPA was seen in patients of short as well as long duration of diabetes, plasma and urine FPA correlated with duration of diabetes in type I patients. In type I diabetic patients with vascular complications, hyperglycemia induced by an oral glucose challenge was accompanied by elevation of plasma FPA and acceleration of fibrinogen disappearance. These responses were not seen when the patients were treated with intravenous (i.v.) heparin before the glucose challenge. In patients without vascular complications, there was also an acceleration of fibrinogen disappearance and a marginal (not statistically significant) elevation of plasma FPA seen after the FPA response observed in vascular disease patients. In all patients, induced hyperglycemia resulted in a decrease in hematocrit and hemoglobin (blood volume expansion) and an increase in pulse pressure indicating hemodynamic changes. The association of hyperglycemia and hemodynamic changes with augmented thrombin activity is consistent with a mechanism for fibrin formation and deposition based on endothelial injury and/or increased vascular permeability. Fibrin deposition due to such a mechanism may participate in the development of the vascular complications of diabetes.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrinogen; Fibrinopeptide A; Glucose; Hemodynamics; Humans; Male; Middle Aged

Plasma levels of platelet factor 4 (PF4) determined in 58 apparently healthy subjects were found to increase with age. In 66 insulin dependent diabetics, PF4 plasma levels were increased but unrelated to the age of subject. Mean fibrinopeptide A levels were elevated in the diabetics but not correlated to PF4 levels. Activation of the coagulation system with thrombin generation thus seems to be operative in diabetes, but the enhanced platelet activation also observed in this disease is probably not thrombin mediated. No correlation was found between PF4 plasma concentration and the degree of vascular complication, HbA1C, blood glucose, 24-h urinary glucose, serum cholesterol or serum triglycerides.

Topics: Adult; Aged; Aging; Aspirin; Blood Platelets; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Fibrinopeptide A; Humans; Insulin; Male; Middle Aged; Platelet Count; Platelet Factor 4

Plasma thromboglobulin concentrations are raised in diabetes. Although patients with angiopathic complications tend to have the highest thromboglobulin, this distinction is not clearly defined. Diabetic subjects with high thromboglobulin also have increased plasma concentrations of fibrinogen and fibrinopeptide A. Abnormal platelet function, therefore, accompanies changes in the coagulation system and suggests a "prethrombotic" state. Increases in plasma glucose induced by an oral glucose load in diabetics are associated with a decrease in plasma thromboglobulin. The role of these changes in the pathogenesis of microangiopathic complications remains speculative.

Topics: Adolescent; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Blood Glucose; Diabetes Mellitus; Diabetic Angiopathies; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged