Epidemiology of the metabolic syndrome in Hungary.

OBJECTIVES: Hungary has high cardiovascular mortality. Recent studies have revealed a high prevalence of several cardiovascular risk factors, including obesity, diabetes and hypertension. The objective of this study was to assess the prevalence of the metabolic syndrome in Hungary. STUDY DESIGN: Cross-sectional study. METHODS: Within the framework of the Hungarian General Practitioners' Morbidity Sentinel Stations Programme, a random sample of 2006 individuals aged 20-69 years was selected in 2006. Physical examinations, blood sampling and data collection were performed by general practitioners. Information on environmental factors was gathered using a questionnaire. The population prevalence was estimated based on the sample frequencies. RESULTS: The overall response rate was 91%. The age-adjusted prevalence of the metabolic syndrome using the 2009 Harmonized definition was 38% [95% confidence interval (CI) 35-42%] in males and 30% (95% CI 28-33%) in females aged 20-69 years. There were no significant regional differences in the frequency figures. CONCLUSIONS: The high prevalence of the metabolic syndrome is a serious public health problem in Hungary, and remains a major determinant of the high burden of cardiovascular disease.

Screening for metabolic syndrome within a minority ethnic group (adult Gypsy people) in Hungary.

BACKGROUND: Metabolic syndrome occurs more often among people living in poorer social conditions. The health status of the largest minority ethnic group in Hungary lags in many aspects behind that of the general population. METHODS: To estimate the prevalence of metabolic syndrome a screening was initiated in the city of Gyor among subjects aged 20-70 years who declared themselves as Gypsy. Subjects with known diabetes and cardiovascular disease were excluded. The diagnosis of metabolic syndrome was based on the ATP-III criteria. RESULTS: Among the 77 individuals screened (35 men, 42 women, age 46.9 ± 10.6 years, x ± SD) diabetes mellitus was found in 14 cases (18.2 %), and pre-diabetes (impaired fasting blood glucose (IFG) or impaired glucose tolerance (IGT) could be diagnosed in further 14 cases (18.2 %). Individual components of the metabolic syndrome occurred as follows: hypertension in 47 subjects (61.0 %), abnormal waist circumference in 40 individuals (51.9 %), abnormal HDL-cholesterol in 39 cases (50.6 %), abnormal triglycerides in 35 individuals (45.5 %) and abnormal fasting blood glucose in 15 subjects (19.5 %). Within the cohort metabolic syndrome could be diagnosed in 39 individuals (50.6 %) without a significant gender difference (males 20/35 = 57.1 %; women: 19/42 = 45.2 %, p>0.05). CONCLUSION: The occurrence of metabolic syndrome and that of glucose intolerance is high among adult Gypsy people in Hungary. In order to recognise cardio-metabolic risks and to prevent their cardiovascular consequences, continuous health promotion and adequate medical care should be provided for the Gypsy population in Hungary (Tab. 5, Ref. 32).

Hormonal regulation of complement biosynthesis in human cell lines--II. Upregulation of the biosynthesis of complement components C3, factor B and C1 inhibitor by interleukin-6 and interleukin-1 in human hepatoma cell line.

The effect of interleukin (IL)-6 and IL-1 on the biosynthesis of complement components C3, factor B, C2, C4 and C1 inhibitor (C1 inh), as well as that of albumin, was studied in vitro in human hepatoma-derived cell line, HepG2. Measuring the amounts of secreted complement proteins we detected a significant upregulation of C3 by both hormones. The enhancement of the factor B and especially that of C1 inh production was predominant by IL-6. In our experimental system neither IL-1 nor IL-6 affected the biosynthesis of C2 and C4. Albumin secretion was significantly decreased only in the simultaneous presence of IL-1 and IL-6. Detection of the changes in the amounts of C3- and factor B-specific mRNA of HepG2 cells suggests a pretranslational regulation by these cytokines. The secretion of C3 and factor B was markedly potentiated when IL-1 and IL-6 were added together. However only the gene expression of factor B, but not of C3, was found to reveal synergism. IL-6 enhanced the in vitro production of C3 in mouse hepatocytes as well. This effect was greatly potentiated in the presence of histamine.

Hormonal regulation of complement biosynthesis in human cell lines--I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2.

C1 inhibitor (C1inh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of C1r and C1s and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human gamma-interferon (gamma-IFN), has been determined on the production of C1inh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of C1inh. The most pronounced effect was detected in the concn range 10(-7)-10(-9) M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10(-4) M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant gamma-IFN markedly increased the gene expression and secretion of C1inh. This effect of gamma-IFN was abolished by histamine.

Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection.

OBJECTIVE: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-ADE) of HIV infection which may play a significant role in the progression of HIV-disease. METHODS: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1IIIB and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. RESULTS: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. CONCLUSION: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.

Ragweed allergy: correlation between skin reactivity and in vitro complement activation.

Recently we have reported on several observations which indicate that allergen-induced complement activation contributes to the development of the symptoms of ragweed allergy. In the present paper a new finding that supports this assumption is summarized. In 48 ragweed-allergic patients individual skin reactivity to ragweed allergen extract (RWA) was assessed using dilution skin prick testing. Sera of these patients were incubated with 20, 100, and 400 U/ml RWA and generation of two complement activation products, alternative pathway C3-convertase (C3bBbP) and terminal pathway activation complex (C5b-9) was measured by ELISA methods. A strong positive correlation (Spearman correlation coefficient r = 0.495, P = 0.0004, and r = 0.454, P = 0.0012, respectively) was found between individual skin reactivity to RWA and C3bBbP generation induced by 20 and 100 A allergological units/ml (U/ml) RWA. This finding further supports the role of complement activation products in the aggravation of the basic IgE-mediated immunopathology of ragweed allergy.

In vitro complement activation by ragweed allergen extract in the sera of ragweed allergic and non-allergic persons.

Ragweed allergen (RWA)-induced complement activation in sera of 40 RW allergic patients and of 40 non-allergic controls was investigated. After treatment of the sera with RWA, levels of C3a, C5a, C3bBbP, C1rC1sClinh, SC5b-9 and granulocyte-aggregating activity were determined. Concentration of RW-specific IgG was also measured. After RWA treatment dose-dependent complement activation was detected in sera of RW allergic and non-allergic persons. C3a generation was observed mostly in the sera of RW allergic individuals, while levels of C3bBbP and of RW-specific IgG were significantly higher in sera of allergics, and a strong correlation was found between these two parameters. In a prospective clinical study, a significant positive correlation was observed between the extent of RWA-induced alternative pathway (AP) activation and the severity of symptoms of allergic rhinoconjunctivitis that were developed in a 4-week period subsequent to blood sampling. These observations suggest that complement activation has a role in the development of the symptoms of RW allergy.

FN-C1q and C1 INH C1r-C1s complexes as indicators of complement activation in patients with chronic lymphocytic leukaemia.

We have previously found low levels of C1 and C4 INH in the sera of chronic lymphocytic leukaemia (CLL) patients. Hypocomplementaemia was supposed to be the consequence of a permanent activation of the classical pathway. We have compared the levels of C1 INH-C1rC1s and C1q-FN complexes in the sera of 95 CLL patients and 100 healthy controls, because these complexes are known to be formed in the early stage of classical pathway activation. A significant increase in the level of both types of complexes was found in sera of CLL patients as compared to the controls. These findings support the assumption that the classical complement pathway is activated in the patients with CLL.

[Plasma homocysteine levels in hyperinsulinemic patients]. / Hyperinsulinaemiás egyének plazma homociszteinszintje.

In order to evaluate the clinical characteristics of metabolic syndrome, a screening procedure was performed and in a cohort of middle-aged (40-60 years) hyperinsulinaemic (fasting plasma insulin > 15 microU/ml) and/or postprandial [120 min after 75 g glucose load] insulin > 45 microU/ml) subjects (n = 91; men/women: 38/53; age mean +/- SD 47.6 +/- 4.3 years; body mass index: 34.6 +/- 4.9 kg/m2; waist-hip ratio: 0.92 +/- 0.07; actual blood pressure 146 +/- 16/87 +/- 9 mmHg; fasting insulin: 24.2 +/- 11.3 microU/ml; postprandial insulin 125.5 +/- 103.8 microU/ml; serum LDL-cholesterol: 3.73 +/- 1.09 mmol/l; HDL-cholesterol: 1.12 +/- 0.30 mmol/l; triglycerides: 2.97 +/- 2.38 mmol/l; uric acid 279 +/- 79 mumol/l) plasma fasting homocysteine, vitamin B12 and folic acid levels were simultaneously determined. The values were separately evaluated according to the stages of glucose tolerance (normal glucose tolerance [n = 47]; impaired glucose tolerance [n = 24] and diabetes mellitus [n = 20]). Laboratory normal values were determined in 47 healthy subjects (control group, age: 45.0 +/- 7.8 years, men/women: 19/28). There was no significant difference between hyperinsulinaemic and control subjects regarding plasma homocysteine (9.28 +/- 3.81 mumol/l vs. 9.63 +/- 2.70 mumol/l), folic acid (8.5 +/- 5.9 ng/ml vs. 7.5 +/- 2.1 ng/ml) and vitamin B12 levels (423 +/- 141 pg/ml vs. 356 +/- 121 pg/ml). Plasma homocysteine levels were significantly (p < 0.001) higher in hyperinsulinaemic men than women (11.34 +/- 4.72 mumol/l [n = 38] vs. 7.86 +/- 2.13 mumol/l [n = 53]). There was no significant difference between subgroups classified according to the stages of glucose tolerance in hyperinsulinaemic groups. Plasma homocysteine values exceeding the upper limit of normal range (> 12.45 mumol/l) were detected at a similar prevalence rate in control (4/47 = 8.5%) and in hyperinsulinaemic subjects (10/91 = 10.9%). A weak but statistically significant correlation was found between plasma homocysteine values and age of subjects (r = 0.222; p < 0.05) whereas a stronger correlation was documented between plasma homocysteine and serum creatinine values (r = 0.658; p < 0.001) in hyperinsulinaemic groups (n = 91). Plasma homocysteine values independently from the stages of glucose tolerance are not elevated in hyperinsulinaemic subjects. Hyperhomocysteinaemia is not a characteristic feature of hyperinsulinism suggesting that plasma homocysteine levels are of no considerable importance in the complex pathomechanism of atherosclerosis at early stages of metabolic syndrome.

Quality of plasma separated from (buffy coat + plasma). An alternative way of blood processing.

A CPD/ADSOL triple-bag system was used to produce plasma, buffy coat and resuspended erythrocytes. These components could be produced in a quadruple-bag system when working according to the conventional technique. In the experimental technique, buffy coat and plasma are transferred together into the satellite bag and are separated from each other only after the second centrifugation. The plasma complement system is not activated and factor IXa is not generated when applying the experimental technique. The quality of plasma meets the international requirements. The blood component processing technique using a triple-bag system is less expensive compared to the quadruple-bag one.

Cardiometabolic risk and educational level in adult patients with type 1 diabetes.

A low educational level and a poor socioeconomic status could be associated with increased risk for chronic diseases. The aim of the study was to evaluate the relationship between the educational level and cardiometabolic risk in adult patients with type 1 diabetes (n = 437; age: 38.0 +/- 10.4 years, duration of diabetes: 19.2 +/- 11.1 years; x +/- SD). Educational levels were classified as low [primary school, n = 56 (12.8%)], middle [high school, n = 251 (57.4%)] or high [university, n = 130 (29.7%)]. The prevalence rate of the metabolic syndrome proved to be higher in patients with low versus high educational levels (ATP-III criteria: 42.9 vs. 21.5%, P = 0.0006). Antihypertensive treatment and cardiovascular diseases were more prevalent in patients with low versus high educational level (46.4 vs. 26.2%, P = 0.01; 12.5 vs. 2.3%, P = 0.02; respectively). Overall glycemic control was worse in patients with low versus high educational level (HbA(lc): 8.8 +/- 1.6 vs. 7.9 +/- 1.4%; P = 0.0006). Patients with low versus high educational level differed significantly regarding smoking habits (smokers: 28.6 vs. 11.6%; P = 0.01) and regular physical activity (5.4 vs. 33.1%; P = 0.0001). Higher prevalence rate of certain cardiometabolic risk factors was associated with low educational level in middle-aged type 1 diabetic patients with relatively long duration of diabetes; therefore, these patients should have priority when preventing cardiovascular complications.

Cardiovascular risk factors characteristic for the metabolic syndrome in adult patients with type 1 diabetes.

UNLABELLED: The prevalence rate and clinical significance of the metabolic syndrome in type 1 diabetic patients are not well established. The aim of this study was to estimate the prevalence rate of the metabolic syndrome in adult patients with type 1 diabetes. Patients with type 1 diabetes (n=533; age: 35.6+/-11.6 years; duration of diabetes: 18.0+/-11.1 years; x+/-SD) were consecutively enrolled from 11 diabetes outpatient departments. Data on medical history, actual treatment, anthropometric and laboratory parameters as well as actual blood pressure were registered while eating habits and physical activity were evaluated by standardized questionnaires. The prevalence rate of the metabolic syndrome according to the ATP-III criteria was 31.1% (29.7% in men, 32.7% in women; p>0.05). Using the IDF criteria a higher overall prevalence rate of the metabolic syndrome (36.2%; [32,8% in men, 39.4% in women; p>0.05]) was observed. Comparing type 1 diabetic patients to the general population, the prevalence rate of the metabolic syndrome proved to be significantly higher in each age-group of patients with type 1 diabetes. According to the stepwise logistic regression analysis the metabolic syndrome in type 1 diabetic patients was associated in a decreasing ranking order of significance with waist circumference, serum triglycerides, female gender, antihypertensive medication, HDL-cholesterol, diastolic blood pressure and serum creatinine. CONCLUSIONS: The metabolic syndrome can frequently be detected and is predominantly associated with higher waist circumference in adult patients with type 1 diabetes in Hungary.

Non-covalently bound C3 enhances lysis of rabbit erythrocytes through the alternative pathway.

Rabbit red blood cells (RaRBC, 3 x 10(7)/ml PBS) were incubated with different amounts of purified human C3 at 37 degrees for 30 min and washed twice in PBS. Different amounts of normal human serum containing 2 mM Mg2+ and 5 mM EGTA were added to the C3-treated and control RaRBC. The extent of lysis was measured after a further incubation at 37 degrees for 40 min. Enhanced lysis was observed with C3-treated RaRBC as compared to control cells. The enhancing effect was dependent on the dose of C3 used for the treatment of RaRBC. Investigation the kinetics of lysis, the lag phase was observed to be significantly shorter with the C3-treated than with the control RaRBC. No enhancement was found when RaRBC were pretreated with preformed C3b fragment. KSCN-treated C3 (C3b-like C3), however, had a lysis-enhancing effect. These results suggest that noncovalently bound C3 molecules may have a role in the initiation and/or maintenance of the alternative pathway activation on activator cells.

Intima-media thickness of the carotid arteries in subjects with hyperinsulinaemia (insulin resistance).

The metabolic syndrome is characterised by hyperinsulinaemia (insulin resistance) leading to an increased risk of atherosclerotic cardiovascular diseases. Carotid intima-media thickness (IMT) can be easily measured to detect early atherosclerosis. In order to evaluate the clinical characteristics of the metabolic syndrome a screening procedure was performed and carotid IMT was determined by high-resolution B-mode ultrasonography in a cohort of middle-aged (40-60 years) subjects who proved to be hyperinsulinaemic [fasting plasma insulin >15 microU/ml and/or post-prandial (120 min) insulin > 45 microU/ml; n = 91; men/women: 35/56; homeostasis model assessment (HOMA)-index: 6.42 +/- 3.65; x +/- SD]. Subjects known to have diabetes were not involved. Subjects were divided into subgroups according to the stages of glucose intolerance (normal glucose tolerance, n = 46; impaired glucose tolerance, n = 26; diabetes mellitus, n = 19). As controls, age- and sex-matched non-diabetic and non-hyperinsulinaemic subjects (n = 20; HOMA-index: 2.09 +/- 0.85) were investigated. The values of IMT of the internal carotid arteries were higher in hyperinsulinaemic subjects than in controls (0.93 +/- 0.39 mm vs 0.57 +/- 0.13 mm,p < 0.001), whereas the lumen diameter proved to be smaller than in control subjects (5.04 +/- 0.75 mm vs 5.45 +/- 0.71 mm; p < 0.05). In hyperinsulinaemic subjects only a trend of increasing IMT values and that of decreasing lumen diameter of the internal carotid arteries were observed when subgroups classified according to the stages of glucose intolerance were compared. No significant changes in IMT or lumen diameter of the common carotid arteries were observed. Early and asymptomatic signs of atherosclerosis could be detected in middle-aged subjects who proved to be hyperinsulinaemic in a screening procedure. The prevention of clinically manifest cardiovascular diseases in these subjects could be of great importance.

Concentration of C1 inhibitor in sera of healthy blood donors as studied by immunoenzymatic assay.

One hundred and forty sera from healthy blood donors (age 19-30 years) were studied for the concentration of C1 inhibitor. The determinations were performed by enzyme-linked immunosorbent assay with the use of specific anti-C1 inhibitor antibodies fixed to the wells of a microplate and peroxidase labeled as the second layer. The geometric mean of the C1 inhibitor value was 0.25 g/l with a standard deviation of 0.09 and a standard error of 0.0077 g/l while the median and mode values were equal to 0.27 g/l. The technique is relatively simple and can be used for the screening of hereditary or acquired angioedema. The technique can be applied also for the study of population differences in the C1 inhibitor concentration and for the study of its synthesis in in vitro systems.

Comparative study of the complement-activating and specific IgE-binding properties of ragweed pollen allergen.

Previous reports have defined the capacity of ragweed pollen extract (RWA) to activate human complement (C) in fluid phase through the classical pathway and have ascertained a strong correlation between the extent of complement activation and the severity of symptoms of allergic rhinoconjunctivitis during the ragweed blooming season. In the present study the complement-activating and specific IgE-binding capacities of various ragweed allergen preparations were compared. Elimination of physically adsorbed (flavonoid) pigments from the allergenic proteins had no significant effect on their complement-consuming capacity, although the process strongly diminished specific IgE binding. Removal of an IgE-binding trypsin inhibitor from RWA significantly enhanced RWA-induced complement activation, whereas it did not change IgE binding. These findings indicate that neither the physically adsorbed pigments nor the trypsin inhibitor are involved in complement activation by ragweed pollen allergens, and suggest that complement activation and specific IgE binding are distinct molecular properties of ragweed pollen allergen.

The severity of clinical symptoms in ragweed-allergic patients is related to the extent of ragweed-induced complement activation in their sera.

We have previously reported a correlation between the extent of ragweed allergen (RWA)-induced in vitro serum complement activation and the symptom scores registered daily during the ragweed (RW)-blooming season in RW-allergic patients. The present study was performed in 22 15-17-year-old RW-allergic adolescents. Serum samples were incubated with 100 micrograms/ml RWA, and the generation of different complement activation products was measured by ELISA or RIA. Symptom scores were registered for 4 weeks during the RW-blooming season. The patients were divided according to the extent (low or high) of the generation of complement activation products, and symptom scores registered in the two groups were compared by two-way ANOVA. Significantly higher symptom scores were obtained in the high than in the low complement activation group (P values: 0.049 for C1rC1sC1inh, 0.022 for C3bBbP, 0.015 for C5b-9, 0.0001 for C3a, and 0.0008 for C5a). Similar results were obtained at the measurement performed in the sera obtained from the same patients half a year before the season (P values: 0.022 for C3bBbP, and 0.005 for C5b-9). These findings indicate that complement activation induced by the allergen may enhance the clinical symptoms of RW allergy.