[Relationship between platelet hyperactivation and dyslipoproteinemia in diabetic nephropathy]. / A diabeteses nephropathiát kísérö dyslipoproteinaemia és a thrombocyta aktiváció összefüggése.

The relationship between the secundaer hyperlipidaemia and pathological platelet activation was examined in 40 insulin-treated diabetic patients without nephropathy and 21 with nephropathy. Diabetic nephropathy was recorded with the measurements of serum creatinine, serum beta 2-microglobulin, and urine albumin excretion. Haemostasis and lipoprotein metabolism were characterized with determination of platelet aggregation, plasma beta thromboglobulin, thromboxane-B2, serum triglyceride, HDL and LDL cholesterol concentration, respectively. In the normalbuminuric group serum triglyceride and thromboxane-B2 positively correlated. In the nephropathic group serum cholesterol and beta thromboglobulin, as well as LDL and beta thromboglobulin, finally, LDL and thromboxane-B2 showed significant positive correlation. In diabetic patients without nephropathy platelet aggregate ratio was in positive correlation with the serum triglyceride, while the ED50-S elevated with the increase of serum cholesterol and LDL. The nephropathic group exhibited no such parallelisms. However, there were significant correlations of LDL with serum creatinine in both groups of diabetic patients. Our results seem to indicate that the increase of LDL could be associated with the change of LDL structure. Interactions of modified LDL and the platelet membrane might contribute to the platelet hyperactivation both in the nephropathy-free and nephropathic cases.

Platelet function in male diabetics with and without macrovascular complications.

Changes of platelet aggregation in relation to macroangiopathy and to some of its risk factors were observed in microangiopathy-free, well-controlled type 1 diabetic males. Platelet aggregate ratio was generally lower in patients (n = 77) than in age-matched healthy subjects (n = 48). In the absence of cigarette smoking, hypertension, obesity and hypercholesterolemia (n = 25) in vitro platelet hyperaggregation was found induced with epinephrine, collagen or arachidonic acid, and to a lesser degree with ADP. There was no change in the presence of at least one risk factor in addition to diabetes (n = 29), but there was a further significant increase in platelet aggregation when overt coronary, cerebral or peripheral artery disease was present (n = 23).

Elevated levels of plasma and urine beta-thromboglobulin or thromboxane-B2 as markers of real platelet hyperactivation in diabetic nephropathy.

Serum creatinine, immunoreactive serum and urine beta 2-microglobulin, plasma and urine thromboglobulin, plasma thromboxane-B2 levels and daily protein excretion were determined in 61 insulin-treated diabetic patients, comparing the different patient groups (complication free, nephropathy without and with azotaemia) with control subjects. In the groups of diabetic patients, plasma and urine beta-thromboglobulin (BTG) and plasma thromboxane-B2 levels were higher than in the controls. There was a significant positive correlation between urine BTG and beta 2-microglobulin in the group without complication, and between the plasma BTG and beta 2-microglobulin, and plasma BTG and thromboxane levels in the diabetic group with azotaemia. In contrast to some previous assumptions, the increased level of plasma BTG reflects a real platelet hyperactivation in patients with diabetic nephropathy. At the same time, urine BTG also increases. Determination of urine BTG is more simple with less possibility of methodological error.

[Plasma and urine beta-thromboglobulin determination in the detection of thrombocyte hyperactivation in diabetic nephropathies]. / A plasma és a vizelet béta-thromboglobulin meghatározás a diabeteses nephropathiát kísérö thrombocyta hyperaktiváció kimutatásában.

Serum creatinine, immunoreactive serum and urine beta-2-microglobulin, plasma and urine thromboglobulin, plasma thromboxane-B2 levels and daily protein excretion were determinated in 61 insulin treated diabetic patients, comparing the different patient groups (complication free, nephropathy without azotaemia and nephropathy with azotaemia) with the control subjects. In the groups of all diabetic patients plasma and urine beta-thromboglobulin and plasma thromboxane-B2 levels were higher that in the controls. There was a positive significant correlation between urine beta-thromboglobulin and beta-2-microglobulin in the group without complication, and between the plasma beta thromboglobulin and beta-2-microglobulin, and plasma beta thromboglobulin and thromboxane levels in the diabetic group with azotaemia. In contradiction to some previous assumptions, the increased level of plasma beta-thromboglobulin reflects a real platelet hyperactivation also in patients with diabetic nephropathy. At the same time urine beta-thromboglobulin also increases. Determination of urine beta-thromboglobulin is more simple with less possibility of methodological error.

[Correlation of thrombocyte reactivity and serum levels of HbA1c, cholesterol and creatinine in diabetes mellitus]. / A thrombocyta reaktivitás összefüggése a HbA1c, a serum cholesterin és a serum creatinin értékekkel diabetes mellitusban.

The thrombocyte reactivity and values of HbA1c, serum cholesterine and creatinine have been examined in 121 insulin-treated and 70 not-insulin-treated diabetic patients and in 98 healthy persons. The thrombocyte functions of patients ranged according to the microangiopathic complications and of control groups matched according to age and sex were analysed with comparative statistics. Positive correlation was found in diabetes between the serum creatinine and cholesterine levels and the aggregating agents' (adrenaline, ADP, and collagen) limit concentrations (p less than 0,05-0,001). Close correlation seems to be between the worsening of renal functions and the decrease of thrombocyte sensitivity in diabetes: The hypercholesterinemia observable in nephropathic diabetes did not lead to the hyperaggregability known in familial hypercholesterinemia. Thus it appears likely that the cholesterine-level increase in the serum does not influence directly, but rather by the effects in connection with its origin, differently the thrombocyte reactivity.

[Necrobiosis lipoidica without diabetes mellitus (diagnostic and therapeutic possibilities)]. / Necrobiosis lipoidica diabetes mellitus nélkül (diagnosztikus és terápiás lehetöségek).

The goal of the present study was to follow the clinical behaviour of 6 non diabetic patients (5 females and 1 male, aged 23-68) suffering from necrobiosis lipoidica. Thickening of the basalmembrane of capillaries could be confirmed by electron microscopy, although the histological structure of skin alterations are not different from those observed in diabetes mellitus. Three patients (2 females and one male) showed impaired glucose tolerance, 2 other patients had increased levels of total cholesterol, whereas one patient suffered from both metabolic disturbances. After treatment with ASA (acetylsalicylic acid, 1.0 g/day) and dipyridamole (200 mg/day) for six weeks, the decrease of platelet in vitro aggregation in platelet rich plasma could be observed by stimulation with arachidonic acid, epinephrine, ADP and collagen, respectively. Healing of the exulceration of skin lesion could be detected by the use of the combined treatment of ASA and dipyridamole in 4 cases.

[Distribution of lipoprotein fractions in men with arteriosclerosis obliterans]. / A lipoprotein frakciók megoszlása arteriosclerosis obliteransban szenvedö férfiakban.

The fasting serum total cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol and HDL-cholesterol were determined in fifty male patients with arteriosclerosis obliterans (ASO) confirmed by angiography. Twenty five of the patients were hyperlipidemic and significantly elevated concentration of atherogenic lipoproteins could be demonstrated compared to age matched control group of healthy subjects (n = 20). The HDL-cholesterol level in the patient group was significantly decreased even if comparing normolipemic patients to controls. In the postprandial phase of cholesterol loading (600 mg) the serum total cholesterol, LDL-cholesterol and HDL-cholesterol levels did not change in both groups. A marked increase in serum total triglyceride, VLDL-cholesterol and VLDL/HDL-cholesterol ratio was detected and the differences between the two groups regarding these lipoprotein fractions were increased. The importance of cholesterol-rich VLDL in ASO and its relationship to familial dysbetalipoproteinemia are discussed.

[Differences in platelet aggregation in various microangiopathic complications of diabetes mellitus]. / A thrombocyta aggregabilitas eltérései a cukorbetegség egyes microangiopathiás szövödményeiben.

In vitro platelet aggregometry with epinephrine, adenosine-diphosphate, collagen and arachidonic acid was performed in 201 patients with diabetes, and in 106 healthy subjects. Those patients who were free of nephropathy showed hyperaggregability to collagen and arachidonic acid, and also to epinephrine and adenosine diphosphate, when neuropathy occurred. Patients with nephropathy, both with and without azotaemia, had diminished platelet responses to each of the four aggregating agents as compared to age- and sex-matched controls. Aggregability was not dependent on type of diabetes. It is concluded that diabetic nephropathy is characterized by decreased in vitro reactivity of platelets. Further researches are necessary to explain in vitro hypoaggregability besides the numerous evidence of in vivo hyperfunction of platelets in diabetes.

[Clinical significance of beta-2-microglobulin in diabetes mellitus]. / A beta-2-mikroglobulin klinikai jelentösége diabetes mellitus-ban.

The beta-2-microglobulin (B2M) level of the serum and urine was determined in 61 diabetics and 15 control patients by enzyme-immunoassay, to asses the value of B2M in clinical diagnosis. In patients with daily protein excretion exceeding 300 mg there was a significant positive correlation between serum creatinine, daily (24-hour) protein excretion, and B2M level of the serum and urine. In patients with less than 300 mg and in those with more than 300 mg daily protein excretion the B2M levels of the serum and urine were significantly higher than in the controls. Serum creatinine level underwent a significant rise only in patients with more than 1000 mg daily protein excretion. Determination of the B2M level is a sensitive method in the diagnosis of diabetic nephropathy. Simultaneous measurement of B2M level in the serum and urine detects nephropathy at an early stage and thus it may be of value in the prevention of the disease.

Platelet hyper- and hypoaggregability in different microangiopathic complications of diabetes mellitus.

In vitro platelet aggregometry was performed in 201 patients with diabetes mellitus, and in 106 controls. The complication-free and retinopathic patients showed hyperaggregability to collagen and arachidonic acid, and also to epinephrine and adenosine diphosphate when neuropathy occurred. Patients with nephropathy, both with and without azotemia, had diminished in vitro platelet responses to each of the four stimuli as compared to age- and sex-matched controls. These characteristics were independent of the type of diabetes. It is concluded that diabetic nephropathy is characterized by reduced platelet in vitro reactivity. Further research is necessary to explain in vitro hypoaggregability in contrast to the numerous proofs of in vivo hyperfunction of platelets in diabetes.

Sex- and age-dependence of platelet aggregation in diabetes mellitus.

Platelet aggregate ratios (PAR) were determined, and threshold concentrations (ED50) of epinephrine, adenosine diphosphate (ADP), and collagen were estimated by platelet aggregometry in 88 IDDM and 52 NIDDM patients without hyperlipidaemia or azotaemia, and in 106 healthy volunteers to revise the question of hyperaggregability in diabetes. ED50-s showed a tendency for negative correlation with age, significant in female but not in male controls. Similar trends were obtained in IDDM and NIDDM females, but were not in IDDM and NIDDM males. The ED50-s of different aggregating agents positively correlated with each other. ED50-s were higher in men than in women in both controls and IDDM patients. Similar but minor differences were observed between women and men in NIDDM. IDDM patients had significantly lower PAR and collagen ED50, and a tendency for epinephrine and ADP to be lower as compared to the sex- and age-matched controls. The differences of PAR were the same, while those of ED50-s were diminished in older NIDDM patients compared to the matched controls. It is concluded, that the previously observed general hyperaggregability in diabetic patients may have partly resulted from sex- and age differences. Threshold concentrations should be compared to sex- and age-matched controls.