We studied 115 patients with uncomplicated maturity-onset diabetes mellitus, 55 males and 60 females; patients were divided into 7 groups according to the hypoglycemic therapy (diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin). All patients were tested for a prethrombotic state by the simultaneous determination of the following parameters: ADP-induced platelet aggregation, Factor VIII as antigen and procoagulant activity and the plasma levels of fibrinogen and antithrobin III. Our results show that these parameters were markedly altered in diabetic patients when compared to apparently normal subjects of the same age; on the contrary, differences between groups of diabetic patients were very slight and hardly ever statistically significant. These results suggest that the prethrombotic alterations of hemostatic system are very similar in all groups of diabetic patients; this is true also for patients submitted to diet alone, i.e. with slight and usually recent-onset diabetes mellitus. In conclusion, our study suggests the opportunity, at least from the theoretical point of view, of systematic antiaggregant and/or anticoagulant treatment(s) in maturity-onset diabetes mellitus, whose severe and precocious prethrombotic alterations seem to be independent of the hypoglycemic treatment applied.

Adenosine Diphosphate↗

PubMedDate not supplied

Plasma fibronectin, von Willebrand factor antigen, and blood rheology. Association with diabetic microvascular disease.

Plasma fibronectin might play a role in the pathogenesis and progression of diabetic microvascular disease. To test this hypothesis we measured plasma fibronectin, von Willebrand factor antigen, fibrinogen, erythrocyte filtrability, whole-blood viscosity, proteinuria and albuminuria in 25 control subjects and 29 diabetic patients with and without microvascular complications. Plasma fibronectin was significantly higher in the diabetic patients, especially in those with retinopathy and nephropathy. A significant correlation between fibronectin and von Willebrand factor antigen was found in both patients with and without microangiopathy (p less than 0.001). In diabetic patients with and without microvascular complications, several significant correlations were found between increased fibronectin levels and reduced erythrocyte filtrability (p less than 0.001) and between the increase of fibronectin and whole-blood viscosity (p less than 0.001). Furthermore, a significant correlation was found between plasma fibronectin levels, proteinuria (p less than 0.001) and albuminuria (p less than 0.001). The relationship between plasma fibronectin and changes of blood rheology may be important for the occurrence and progression of diabetic microangiopathy.

Aged↗

PubMedDate not supplied

Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy.

Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p less than 0.001), fibronectin (p less than 0.001) and fibrinogen (p less than 0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p less than 0.05 at shear-rate of 450 and 225 s-1; p less than 0.01 at 90 s-1; p less than 0.001 at 4.5 and 2.25 s-1), plasma viscosity (p less than 0.001) and lower erythrocyte filtrability (p less than 0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p less than 0.01) and nephropathy (p less than 0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus.

Blood Pressure↗

PubMedDate not supplied

Hypoglycemic treatments and the fibrinolytic system in maturity-onset diabetes mellitus without thromboembolic manifestations.

The fibrinolytic system was investigated in 115 patients with maturity-onset diabetes mellitus in good metabolic control and without thromboembolic manifestations. The patients were divided into 7 groups according to the hypoglycemic therapy: diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin. Our results indicate that in maturity-onset diabetes both fibrinolytic activity and inhibitors of fibrinolysis are increased. The enhanced fibrinolytic activity was not affected by different hypoglycemic drugs, whereas the main antiplasmins showed wide variations in the different treatment groups. In particular, a significant reduction of alpha 2M was observed in patients on glibenclamide therapy. In conclusion, our study showed that the high fibrinolytic state seems to be a constant element in diabetes, and that the different behaviors of the fibrinolytic system, reported by various authors in patients taking different hypoglycemic drugs, could be explained by the wide range of plasmin inhibitor levels observed in these conditions.

Aged↗

PubMedDate not supplied

Changes of plasma protease inhibitors in late pregnancy, during delivery and puerperium in normal women and in preeclampsia.

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Adult↗

PubMedDate not supplied

Activators and inhibitors of the fibrinolytic system in maturity-onset diabetes mellitus without thromboembolic manifestations.

In patients with maturity-onset diabetes mellitus without thromboembolic manifestations, significant increases in both fibrinolytic and antifibrinolytic activity were demonstrated. The increased fibrinolytic activity observed under basal conditions could be due to the continuous release of plasminogen activators from damaged endothelial cells. This hypothesis is supported by the fact that the higher fibrinolytic activity observed in diabetics is followed by a lesser increase in fibrinolytic activity than in controls after the venous occlusion test. The main antiplasmins, except alpha 2-antiplasmin, were significantly higher in diabetics, and their levels were not affected by sex, metabolic regulation, retinopathy, duration of the disease or cholesterolemia. On the contrary, weight, therapy and triglyceridemia significantly influenced the levels of some antiplasmins. Furthermore, hypertriglyceridemia and hypercholesterolemia were associated with a reduction of fibrinolysis. Thus, these conditions may further increase the risk of thromboembolic complications of diabetes mellitus.

Aged↗

PubMedDate not supplied

Plasma levels of protease inhibitors in acute myeloid leukemia at the onset of the disease and during antiblastic therapy.

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Adolescent↗

PubMedDate not supplied

Na(+):K(+):ATPase mRNA expression in the kidney during adaptation to sodium intake and furosemide treatment.

Nephron tubular epithelium possesses the capacity of adaptation to any salt ingestion condition. The mechanism of adaptation is due in part to an increase in the activity of Na(+):K(+):ATPase at the basolateral membrane. The goal of the present study was to analyze the long-term regulation of the Na(+):K(+):ATPase alpha(1)-subunit mRNA expression during changes in NaCl metabolism. Male Wistar rats given a normal, high, or low NaCl diet, and intraperitoneal administration of the loop diuretic furosemide from 12 h to 7 days were studied. Rats were kept in metabolic cages 4 days before and throughout the study to determine daily urinary electrolyte excretion and osmolarity. At the end of each experimental period, creatinine clearance and serum electrolytes were also measured. Total RNA was extracted from each individual cortex or outer medulla and from pooled inner medullas using the guanidine/cesium chloride method. Na(+):K(+):ATPase alpha(1)-subunit mRNA expression was assessed by nonradioactive dot-blot analysis. Experimental maneuvers were well tolerated and all groups developed the appropriate renal response to each experimental condition. Urinary sodium excretion was significantly higher in rats administered a high sodium diet or furosemide and lower in rats treated with a low sodium diet after 7 days of treatment. Glomerular filtration rate was similar among all groups. However, the level of expression of the Na(+):K(+):ATPase alpha(1)-subunit did not change in any model. Nephron adaptation to the modification in NaCl intake or furosemide administration over 7 days did not include changes in Na(+):K(+):ATPase alpha(1)-subunit mRNA levels.

Adaptation, Physiological↗