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BACKGROUND: Glucose-dependent insulinotropic peptide (GIP) provides a novel link between the immune system and the gut, although results from different experimental and observational studies are contradictory, ranging from anti-inflammatory, through neutral to pro-inflammatory action of GIP. Thus, the aim of this study was to analyze inflammatory pathways on the level of gene expression and circulating inflammatory markers in relation to plasma GIP level. SUBJECTS/METHODS: The study included 128 obese adults. Two groups of obese subjects were created according to fasting GIP levels, with cutoff point at the 66th percentile and compared in respect with molecular and circulating markers of inflammation. GIP, interleukin (IL)-6 and adipokines: leptin, adiponectin, visfatin were measured by enzyme-linked immunosorbent assay. Inflammatory markers: monocyte chemoattractant protein-1 (MCP-1), sE-Selectin, sVCAM-1, sPECAM-1 were studied at fasting and after nutrient challenges. Gene expression in blood cells was determined by human gene microarray. RESULTS: Obese patients with high GIP levels had elevated fasting glucose (Q2 (Q1-Q3): 5.6 (5.0-6.0) vs 5.0 (4.8-5.4), P<0.001), homeostasis model assessment of insulin resistance (Q2 (Q1-Q3): 3.68 (2.72-5.42) vs 2.70 (2.13-4.33), P=0.021), thus increased markers of insulin resistance as well as elevated inflammatory markers Il-6 (Q2 (Q1-Q3): 1.34 (1.0-2.04) vs 1.12 (0.76-1.64), P=0.045), MCP-1 (Q2 (Q1-Q3): 363 (287-447) vs 323 (263-389), P=0.026). Leptin to adiponectin ratio was significantly associated with fasting plasma GIP levels (ß (95% CI): 0.84 (0.10-1.59)) independently of glucose levels. sE-Selectin was found to be a factor influencing GIP response to oral glucose intake (ß (95% CI): 0.47 (0.14-0.81)) and sVCAM was found to be a factor influencing GIP response to high-fat meal intake (ß (95% CI): 0.19 (0.01-0.37)). We identified 32 genes of inflammatory pathways differentially expressed in subjects with a high plasma GIP level compared to low GIP. Most upregulated genes play a role in leukocyte chemotaxis and tissue infiltration. CONCLUSIONS: These findings support the hypothesis that increased GIP signaling has a role in chronic low-grade inflammation.

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Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin/adiponectin ratio, higher visfatin and interleukin-6 levels. The fat containing meals stimulate the long-lasting release of incretins, mainly GIP, parallel to the increase of the markers of low grade inflammation associating obesity in metabolic syndrome. The possibility of use of the postprandial (OLTT) GIP release measurement for the low grade inflammation progress in MS patients is suggested.

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OBJECTIVE: Recently there has been widening stream of research on the relationships between obesity and mental disorders. Patients with obesity seem to be prone to developing bipolar spectrum disorders and they present with specific personality traits. The aim of this study was to analyze the associations between obesity, bipolarity features, and personality traits. PATIENTS AND METHODS: A nested case-control study was performed. Patients with obesity constituted the sample of cases (N = 90), and healthy individuals were ascribed to the control group (N = 70). The lifetime presence of bipolarity features was analyzed with the Mood Disorder Questionnaire (MDQ), while personality traits were assessed with the NEO-Five Factor Inventory (NEO-FFI). RESULTS: Bipolarity features were more prevalent in the patients with obesity, as compared to healthy individuals. Patients with obesity had both higher mean value of MDQ score (p = 0.01) and a higher proportion of subjects with MDQ score ≥ 7 points (p = 0.012) as well as lower score on the NEO-FFI openness to experience (p > 0.001), compared to control subjects. Using multivariate model, in patients with obesity, a significant positive correlation between bipolarity and neuroticism, and negative with agreeableness and conscientiousness was established. Such relationship was not observed in control subjects. CONCLUSIONS: In the population of patients with obesity, there is a specific combination between bipolarity and personality traits (high-trait neuroticism, low-trait conscientiousness, and low-trait agreeableness). This may have some consequences for both pharmacological and psychological management of such patients.

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The aim of the study was to examine the allelic frequency of the -3826A > G mutation of UPC1 in patients with familiar obesity and to investigate putative association of this polymorphism with metabolic disorders. One hundred and eighteen overweight /obese patients participated in the study. The UCP1 polymorphism was determined by RFLP. Glucose, lipid, insulin and leptin levels were measured both during OGTT and OLTT. The majority of patients had a homozygous A/A genotype (51,38%), while 14,68% had a G/G genotype. We found no significant association of the G allele with either BMI or glucose tolerance. Patients with the homozygous G/G genotype had significantly higher fasting levels of TG (p < 0.04) and decreased levels of HDL-cholesterol (p = 0,004). They also had an increased concentration of FFA and the rise of TG levels during the OLTT compared to controls was significant (p = 0,058). In addition, the carriers of the G/G genotype had the lowest insulin levels both during OGTT and OLTT. In our study we have demonstrated that the -3826A > G polymorphism of UCP1 does not play a major role in the development of obesity and/or disturbances of glucose metabolism. However, the increased levels of TG and FFA and decreased levels of HDL observed in carriers of the G allele suggest FFA-induced impairment of the HDL turnover and disturbance of the beta-cell function, both of which are risk factors for endothelial injury.

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UNLABELLED: The endothelial dysfunction in cardiological syndrome X has been studied mainly by invasive methods and by measuring vasoactive mediator (nitric oxide (NO), endothelin-1) levels. Other parameters evaluating this dysfunction (defined as an imbalance between vascular relaxing and contracting factors, between procoagulant and anticoagulant or growth-inhibiting and growth-promoting substances) have not been used. METHODS: Twenty-five non-diabetic patients (16 men, 9 women) with cardiological syndrome X and 10 healthy volunteers (5 men, 5 women) were examined. Biochemical parameters: ET-1, the end products of nitric oxide metabolism (NOx), VEGF, vWF, betaTG, tPA, PAI-1 were measured before and during an ECG exercise tolerance test. The blood concentrations of testosterone and estradiol in men and LH, FSH and estradiol in women were tested. RESULTS: A significantly lower basal concentration of NOx (p=0.01), lower basal NOx/ET-1 ratio (p<0.05) and higher levels of VEGF (p<0.05) were observed in patients with cardiological syndrome X. The male patients also had higher concentrations of estradiol (p<0.05). A significant decrease in tPA concentration and increase in betaTG was noticed during exercise, but with no differences between the study groups. CONCLUSIONS: Endothelial dysfunction in cardiological syndrome X manifests mainly in the regulation of vessel wall tonus. which was revealed by the decrease of NOx level and NOx/ET-1 ratio. VEGF elevation in syndrome X may result from chronic tissue ischaemia due to endothelial dysfunction. Exercise augments the prothrombotic activity of the blood, since a significant elevation in betaTG and decrease in tPA were observed after exercise.

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Since a number of pathological processes such as septic shock, inflammation, graft rejection, diabetes, etc. are associated with a release of nitric oxide (NO), rapid and accurate methods of monitoring of NO concentration are of interest. Various methods for measurement of nitrite and nitrate (NO2-, NO3- ) -- the stable metabolites of NO -- are commonly used for this purpose. In this paper we have shown that the proper Griess procedure for nitrite determination significantly increases the sensitivity of this method. This procedure, supplemented with deproteinization and reduction of nitrates to nitrites in the presence of NADPH-sensitive reductase, can be successfully applied for measurement of NOx levels in human body fluids (serum, urine and CSF). Deproteinization of samples with methanol/diethylether is required and does not influence the sensitivity of detection of NO metabolites. The recovery of the method is 88%+/-6% (n = 30). The NOx concentrations measured by this procedure ranged from 25.0 to 39.0 micromol/l in blood, 4.6 to 14.6 micromol/l in CSF and 0.37 to 2.52 mmol/l (adjusted to creatinine concentration) in urine. The coefficient of variation for this method was between 1.3-2.2%. This method can also be recommended for measurement of NOx produced by cells in tissue cell culture.

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BACKGROUND: The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential hypertension and in control subjects (non-obese, non-diabetic normotensive subjects) was estimated. METHODS: According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output. RESULTS: The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups. CONCLUSION: The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.

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BACKGROUND: The role of nitric oxide (NO) in regulation of systemic blood pressure both in normotensives and in hypertensives remains unknown. OBJECTIVE: To investigate the influence of L-arginine (the substrate for generation of NO) on blood pressure in 30 men (aged 51.5 +/- 7.3 years) with established primary arterial hypertension that was not well controlled. METHODS: The antihypertensive therapy was not discontinued and the patients were administered beta-blockers and calcium antagonists only. On day '0' the patients were administered 250 ml 0.9% NaCl during 180 min intravenously. Then we infused 250 mg/kg L-arginine diluted in 250 ml 0.9% NaCl over 180 min into the antecubital vein for four consecutive days (days 'I'-'IV'). Conventional blood pressure and heart rate measurementws were performed before infusion and every 30 min during infusion. Twenty-four-hour ambulatory blood pressure monitoring (with a SpaceLabs 90207 device) with half-hourly recordings during the daytime and during the night-time was performed on the day of NaCl infusion ('0') and repeated on the day of L-arginine infusion ('II') for all patients. As indicators of generation of NO, blood level of cyclic GMP and urinary concentration of nitrite/nitrate were measured. RESULTS: On all days of L-arginine infusion we found significant falls in systolic and diastolic blood pressures (P < 0.0001) with an accompanying significant increase in heart rate (P < 0.001). The most potent hypertensive effect during infusion of L-arginine was observed on day 'I'. Mean systolic blood pressure decreawsed from 152.1 +/- 20.0 mmHg to a minimum of 123.3 +/- 16.2 mmHg after 60 min of the infusion (by about 19%). The maximal percentage fall in systolic blood pressure was consecutively lower on each day oif L-arginine infusion. It was 14.3% on day 'II', 11.9% on day 'III' and 10.1% on day 'IV'. Similarly, the greatest reduction of diastolic blood pressure was observed during infusion of L-arginine on day 'I'. Mean diastolic blood pressure decreased from 95.9 +/- 13.6 to 80 +/- 9.7 mmHg after 120 min of infusion (by about 17%). On the consecutive days maximal falls in diastolic blood pressure compared with its initial value were 13.5% on day 'II', 10.4% on day 'III' and 9.8% on day 'IV'. Twenty-four-hour ambulatory blood pressure monitoring revealed a significant decrease in diastolic blood pressure during infusion of L-arginine compared with day 0 when 0.9% NaCl was infused. Systolic and diastolic blood pressure variabilities were significantly decreased and the day-night differences in systolic and diastolic blood pressures were increased after infusion of L-arginine. We found a significant correlation between heart rate and systolic blood pressure both during the daytime and during night-time on the day of infusion of L-arginine. An increase in urinary concentration of nitrite/nitrate was observed after administration of L-arginine.CONCLUSION: The present results demonstrate that infusion of L-arginine can influence the systemic blood pressure in hypertensives through NO synthesis. By using ambulatory blood pressure monitoring we documented that the hypotensive effect of L-arginine seems to be limited to the infusion period itself. A decrease in blood pressure variability might imply an increase in sensitivity of baroreceptors or an improvement of autonomic functioning.

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There has been a large amount of progress in the methods of prevention and treatment of ischaemic heart disease (IHD), but the effect of these changes on mortality due to IHD has not been assessed. This paper presents the complex analysis of 10-year trends of incidence, case fatality and mortality due to myocardial infarction (MI) and changes in medical care in the acute phase of MI in residents of one province of Poland-Tarnobrzeg Voivodship, which was the target population of the POL-MONICA Kraków Project (over 280,000 men and women at age 25-64 years). In men, the incidence of MI, which was 335/100,000 in 1984, increased in 1986 to 463/1,000,000 and then was stable until 1993 when it felt to 362/100,000. Mortality from MI, which was 149/100,000 in 1984, increased to 212/100,000 in 1986 and then was stable until 1992, before falling to 173/100,000 in 1993. There were large fluctuations in the incidence and mortality from MI in women i.e. from 58/100,000 to 116/100,000 and from 21/100,000 to 55/100,000 respectively. In 1993 the incidence was 82/100,000 and mortality was 32/100,000. After adding sudden deaths and other fatal events attributed to IHD the mortality figures increased over the ten years of observation by an average of 29% in men and by 28% in women. The average total MI case fatality was 47% in men and 40% in women, with 86% of all deaths due to MI occurring out of hospital. Case-fatality of MI managed in hospital was 11% on average.

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L-arginine (L-Arg) was administered intravenously through 4 consecutive days to 20 males (40-63 years old) with essential hypertension (EH). Significant decrease (p < 0.02) of systolic blood pressure (SBP) was observed only during the first day of the therapy and tachyphylaxis against L-Arg was noticed. The reduction of diastolic blood pressure (DBP) was more marked (p < 0.001). Significant changes in cGMP plasma level and the nitrite/nitrate urine concentration were not observed. L-Arg caused a significant activation of fibrinolysis (p < 0.005). The decrease of platelet activity, measured by the ADP-induced aggregation, after L-Arg administration was not statistically significant. Therefore, L-Arg may play only a secondary role in the treatment of EH.

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The coefficients and trends of mortality in years 1976-1987, based on data of Central Statistical Office, has been estimated in population of men and women aged 25 to 64 years, inhabitants of the Warsaw city region or the county region of Tarnobrzeg province . The trend of decrease of general mortality due to diseases of circulatory system has been statistically significant one similarly as that of mortality due to other heart diseases or ischaemic heart disease in men (group aged 25-34 or 35-44 years) in the Tarnobrzeg province . The analogously significant trend of mortality due to diseases of circulatory system or ischemic heart diseases in men aged 35-44 years has been stated in the Warsaw inhabitants. In the group of women an increase of general mortality has been noted in the youngest age group in Warsaw. In Warsaw and the Tarnobrzeg province in 1987 deaths due to diseases of circulatory system represented 33.2% and 39.9%, respectively, of total death pool among subjects aged 25 to 64 years. The respective percentages in the group of women were 29.1% and 39.4%.

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In years 1984-1986 3639 men and 1885 women were registered with suspected myocardial infarction from right-side Warsaw, simultaneously 2371 men and 917 women with the same suspected disease were registered from the Tarnobrzeg province population. The myocardial infarction diagnosis was confirmed in 54% of men and 43% of women from the Warsaw population as well as in 77% of men and 66% of women from Tarnobrzeg province population. In Warsaw the standardized incidence due to myocardial infarction increased during years of study from 466 to 588/100,000 among men and from 178 to 206/100,000 among women. The analogous increase among the Tarnobrzeg province population was 302 to 559/100,000 among men and 64 to 195 among women. Fatality during 28 days from the onset of the disease did not show any relationship with year of study and corresponded yearly among men to 45% and among women to 37% in Warsaw and to 42% among men and 33% among women in the Tarnobrzeg province . High fatality was noted during first 24 hours of hospitalization (Warsaw: 36% among men and 26% among women, Tarnobrzeg: 39% among men and 32% among women). The highest fatality was noted in the youngest of analysed groups.

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In years 1984-1986 582 men and 338 women have been registered with clinical diagnosis of cerebral stroke. The respective numbers in the Tarnobrzeg province were 340 and 263. Preliminary diagnosis of cerebral stroke was confirmed according to criteria of registration in 82% of men or women from Warsaw and in 81% of men and 84% of women in the Tarnobrzeg province . Standardized incidence due to cerebral stroke was significantly higher in every of analysed years in the Warsaw population both among men and women in compare with that in the Tarnobrzeg province . In both population studied the incidence was significantly higher among men than among women. Standardized fatality during 28 days from the start of sickness was higher in the Tarnobrzeg province population than in the Warsaw population so far as both men and women are concerned. In both populations among men and women the most frequently diagnosis was acute disease of cerebral vessels.

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The findings after the first year of the study are presented. The study population is 282,052 men and women aged 25-64 years, current residents of rural Tarnobrzeg Voivodeship. The population is characterized by a declining linear trend in ischemic heart disease (IHD) mortality in men aged 35-44 years. The myocardial infarction (MI) incidence (per 100,000 residents) is 233 in men and 68 in women. The MI death rates (per 100,000 residents) are 128 for men and 29 for women. The MI 28-day case fatality is 44% for men and 41% for women. The most frequent risk factors are: smoking in men (58%) and obesity in women (40%). Around one-quarter of the men and of the women are hypertensive. The rates for hypercholesterolemia are 9% in men and 13% in women.

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