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Biomedical subjects

Ida Kinalska

Publications and source records attributed to Ida Kinalska.

At least 19 recordsLinked to original sources
PubMed2006

Plasma adiponectin concentration and tumor necrosis factor-alpha system activity in lean non-diabetic offspring of type 2 diabetic subjects.

OBJECTIVE: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin's role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-alpha system. RESEARCH DESIGN AND METHODS: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glucose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-alpha, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated. RESULTS: The insulin sensitivity index, normalized for fat-free mass (M(ffm)) and adiponectin concentrations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P = 0.0046 and P = 0.00058 respectively). TNF-alpha and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL-cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = -0.33, P = 0.027). CONCLUSIONS: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects.

Adiponectin↗
PubMed2006

An alternative spliced variant of circulating soluble tumor necrosis factor-alpha receptor-2 is paradoxically associated with insulin action.

OBJECTIVE: Serum concentrations of soluble tumor necrosis factor-alpha (TNF-alpha) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent study, we provided evidence for the existence of a biologically active form of sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether this circulating DS-TNFR2 is associated with insulin action in humans. DESIGN AND METHODS: Real time PCR (light cycler technology) evaluated DS-TNFR2 expression in monocytes. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Insulin sensitivity was measured using euglycemic hyperinsulinemic clamp (n = 76) and homeostatic model of assessment (HOMA) value in a replication study of 223 subjects. RESULTS: Real time PCR confirmed gene expression of DS-TNFR2 in monocytes from healthy subjects. A significant and positive association was found between serum DS-TNFR2 concentration and insulin sensitivity (P = 0.032, n = 76). This association was most significant in subjects with normal glucose tolerance (r = 0.44, P = 0.002). The subjects in whom DS-TNFR2 was detectable were more insulin sensitive than those with undetectable DS-TNFR2 (42.12+/-22.08 vs 31.71+/- 16.95 micromol x kg(-1) x min(-1), P = 0.039). DS-TNFR2 was inversely associated with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, fasting serum glucose, serum triglycerides and serum uric acid concentration and with the HOMA value (P = 0.03) in the replication study. Circulating DS-TNFR2 declined with increased number of components of the metabolic syndrome. CONCLUSION: Native sTNFR2 and DS-TNFR2 show opposite associations with insulin action. DS-TNFR2 might play a role as a counterpart of the proinflammatory environment associated with insulin resistance.

Adult↗
PubMed2006

[Evaluation of influence of selenium, copper, zinc and iron concentrations on thyroid gland size in school children with normal ioduria].

UNLABELLED: Proper diet with regard to quantity and quality of meals is of vital importance for normal development and functioning of the organism. There are many proofs that environmental factors play an important role in the pathogenesis of goiter. Iodine deficit in diet is best known of all factors contributing to goiter. Deficit of other elements like, iron, selenium, copper and zinc is also essential. The purpose of this study was to evaluate the influence of chosen environmental factors, i.e., iron and trace elements of selenium, zinc and copper--essential for the thyroid functioning on the development of goiter in school children aged 6-13 years with normal ioduria in the Polish population. MATERIAL AND METHODS: In 2002, the study was performed in 4 elementary schools chosen randomly in Białystok and in the Children's Outpatient Clinic of Endocrinology of the Specialist Regional Hospital. The study included 400 children aged 7-13 years from schools and 120 patients at the same age treated with KJ and/or tyroxine for minimum 12 months due to goiter in the Out-patient Clinic of Endocrinology. Basing on the assessment of the thyroid size as well as the criteria of WHO from 1997 year for body surface and sex, children were divided into 2 subgroups: with goiter and the thyroid gland within the norm. Children aged 9-11 years were qualified and chosen from subgroups to further examinations. In both subgroups, blood samples were taken to determine concentrations of iron, selenium, copper and zinc. RESULTS: The mean concentration of selenium in the blood was statistically significantly lower in children with goiter in comparison with children with the thyroid gland within the norm (44.4 +/- 7.8 microg/L vs. 49.2 +/- 9.1 microg/L, p = 0.044) in the study population of school children and the Outpatient Clinic of Endocrinology. No differences of serum iron concentrations were observed in children with goiter and with the thyroid gland within the norm. However, nearly the half (45.5%) of patients with the lower serum concentration of iron (< 60 microg/dL) had goiter despite average 22-month therapy with KJ and/or tyroxine. CONCLUSION: Observed, in spite of proper iodine prophylaxis, 7% rate of goiter occurring in school children suggests other than iodine deficiency factors that influence goiter development. The study proved that the low concentration of iron and/or selenium deficit found in the serum of children with goiter in spite of their treatment with KJ and/or tyroxine may be additional factors influencing the effectiveness of this treatment.

Adolescent↗
PubMed2006

[Tumor necrosis factor-alpha system in patients with gestational diabetes].

Tumor necrosis factor-alpha (TNF-alpha) system is potentially involved in the development of insulin resistance during pregnancy. Plasma concentrations of TNF-alpha and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 +/- 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 +/- 6.0 years). We found that patients with GDM had significantly higher levels of TNF-alpha in comparison to NGT women (1.71+/- 0.92 vs. 1.27 +/- 0.42 pg/ml, p = 0.0175). The differences remained statistically significant after adjusting for BMI (p = 0.027). Plasma levels of sTNFR-1 and sTNFR-2 were only slightly higher in patients with GDM (2.83 +/- 0.79 ng/ml vs. 2.55 +/- 0.99 ng/ ml, p = 0.057 and 7.46 +/- 2.21 ng/ml vs. 6.83 +/- 1.46 ng/ml, p=0.206, respectively). In the group with GDM TNF-alpha concentrations correlated with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT - only with triglyceride levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that early pregnancy BMI was the most predictive indicator of TNF-alpha concentrations in GDM women (p=0.008). In NTG group triglyceride concentrations, as well as BMI in early pregnancy and at the time of sampling were significant predictors, explaining together 62% of the variance in TNF-alpha concentration. In conclusion, increased TNF-alpha concentrations in women with GDM class G1 indicates its contribution to the development of insulin resistance during pregnancy, but the lack of the differences in sTNFR concentrations between the groups studied suggests only moderate TNF-alpha system activation in relatively slim patients treated with diet.

Adult↗
PubMed2005

[The level of IGF-1 and TGF-beta-1 in the blood serum and the thyroid size in children with normal ioduria].

BACKGROUND: Growth factors--IGF-1 and TGF-beta1 are well documented factors regulating proliferation of follicle cells of the thyroid in many experiments in vitro. It has been proved so far that IGF-1 stimulates cellular mitogenesis of thyrocytes, whereas TGF-beta1 inhibits proliferation of follicle cells of the thyroid in experimental conditions. OBJECTIVES: The aim of the study was to evaluate the correlation between serum concentrations of IGF-1 and TGF-beta1 and the size of the thyroid in children with normal ioduria. MATERIAL AND METHODS: In 2002, the study was performed in 4 elementary schools chosen randomly in Białystok and in the Children's Out-patient Clinic of Endocrinology of the Specialist Regional Hospital. The study included 480 children aged 7-13 years from schools and 120 patients at the same age treated with KJ and/or thyroxine for minimum 12 months due to goiter in the Out-patient Clinic of Endocrinology. All children underwent physical examination with palpation of goiter and USG of the thyroid. Iodine concentration was assessed in the morning urine by the catalytic method of Sanedell-Kolthoff. In the second part of the examination, basing on the assessment of the thyroid size as well as the criteria of WHO from 1997 year for body surface and sex, children were divided into 2 subgroups: with goiter and the thyroid gland within the norm. Children aged 9-11 years were qualified and chosen from subgroups to further examinations. In both subgroups (with goiter and normal thyroid gland) blood samples were taken to determine concentrations of TSH, IGF-1, TGF-beta1. RESULTS: The mean values/median of IGF-1 concentration were statistically significantly increased in children with goiter in comparison with children with a normal thyroid (436.2 vs. 343.8 ng/ml, p=0.047). The mean values / median of TGF-beta1 concentration were statistically significantly decreased in children with goiter when compared to children with the thyroid gland within the norm (17.8 vs. 23.9 ng/ml). CONCLUSIONS: The significantly lower concentration of TGF-beta1 in the serum of children with goiter in comparison with the values in children with normal size of the thyroid gland and a positive correlation between the concentrations of IGF-1 and the size of the thyroid (after excluding the influence of age and body surface) seem to confirm a vital role of IGF-1 and TGF-beta1 in the pathomechanism of goiter.

Adolescent↗
PubMed2005

[Evaluation of the thyroid size among school children aged 6-13 with the normal iodine excretion in the urine and the usability of referential values still applied].

BACKGROUND: The evaluation criteria of the enlarged thyroid gland becomes a key problem when analyzing the prevalence of goiter in the population of school children. The review of the literature and own experience indicate lack of a consensus concerning this problem among researchers. Similarly, in the report of WHO in the year 2001 concerning the problem of iodine deficit and goiter endemia, experts did not present universal referential values of the thyroid size in ultrasonography for children population aged 6-15 years living in the regions of proper iodine supply in the diet, thus suggesting the necessity of working out regional norms. OBJECTIVES: The aim of the study was to evaluate the prevalence of goiter in children aged 6-13 years from schools chosen randomly in Białystok with proper iodine supplementation in the study population and to estimate the usability of referential values applied in the assessment of the thyroid size. MATERIAL AND METHODS: In the year 2002, the examination was carried out in 4 elementary schools chosen randomly from Białystok. A total of 480 children aged 6-13 years were included in the study. All children were examined physically with palpation assessment of the thyroid size and had USG of the thyroid. The concentration of iodine was measured in the morning urine. The blood samples were collected to determine hTSH concentration. RESULTS: In palpation, with regard to WHO criteria of the year 2001, the prevalence of goiter was 6.8% in the study population. Applying WHO criteria of 1994 in palpation assessment of goiter increased this percentage up to 18.2%. When using WHO criteria for body surface of 1997 to evaluate goiter by USG, its percentage equaled 7%, whereas taking into consideration referential values for child's age doubled its percentage up to 13.5%. The percentage of goiter increased up to 45.5%, when referential values introduced by Gutekunst et al. were applied. CONCLUSIONS: When evaluating the thyroid size in ultrasonographic diagnostics of goiter in children aged 6-13 years, it seems more purposeful to apply referential values of the thyroid size regarding the body surface and sex (manifesting a child's actual physical development) than to use the norms concerning the calendar age. The prevalence of goiter amounting 7% in the population of school children in spite of adequate iodine prophylaxis suggests other than iodine deficit, factors causing goiter in this population.

Adolescent↗
PubMed2004

Comparison of simple indices of insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

BACKGROUND: Insulin resistance is an important factor in the pathogenesis of type 2 diabetes mellitus and other diseases, collectively known as "metabolic syndrome". The gold standard in measuring insulin resistance is glucose clamp, but this method is difficult to apply in large studies. Therefore, indirect indices of insulin sensitivity are proposed. The aim of the present study was to compare these simple indices with data from clamp studies. MATERIAL/METHODS: We examined 51 obese subjects, 23 with impaired glucose tolerance (IGT), 28 with normal (obese-NGT), and 37 healthy lean controls. Insulin sensitivity was determined with the euglycemic hyperinsulinemic clamp technique. We estimated indices of insulin sensitivity: fasting plasma insulin (INS), logarithm INS (log [INS]), homeostasis model assessment (HOMA), logarithm HOMA (log [HOMA]) and quantitative insulin sensitivity check index (QUICKI). RESULTS: With clamp technique, we demonstrated a decrease in insulin sensitivity in both obese groups vs controls, and also in IGT compared to NGT subjects. The differences were significant when we used other indices of insulin sensitivity, except those for INS, log [INS] and HOMA between the two obese groups. Indirect indices correlated with insulin sensitivity derived from clamp in the whole population and in the subgroups of control and NGT-obese subjects. In the IGT group, only the correlations with log [INS], log [HOMA] and QUICKI were significant. CONCLUSIONS: Simple indices may give valuable information about insulin sensitivity in large studies. Indices based on log-transformed plasma glucose and insulin levels are recommended in subjects with IGT.

Adult↗
PubMed2004

Serum levels of soluble TNFalpha receptors (sTNFR1 and sTNFR2) during corticosteroid treatment in patients with Graves' ophthalmopathy.

UNLABELLED: TNFalpha was shown to play an important role in the autoimmune inflammatory process of Graves' ophthalmopathy (GO). In our previous study we found no significant changes in serum TNFalpha levels in GO patients. The aim of the present study was to estimate an influence of corticosteroids on serum levels of TNFalpha receptors (sTNFR1 and sTNFR2) in GO patients and to assess their potential as a guideline of immunosuppressive therapy. We detected serum sTNFRI and sTNFR2 in three groups of subjects: 18 patients with clinical symptoms of ophthalmopathy [Clinical Activity Score (CAS) > or = 4, anamnesis of GO > or = 1 yr], 16 patients with Graves' disease without ophthalmopathy (Gd) and 14 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of serum sTNFR1 and sTNFR2 were determined by ELISA. Serum levels of sTNFR1 were significantly higher in GO individuals as compared to the control group (p < 0.01). We have found a significant decrease in sTNFR1 concentration in corticosteroid-respondent patients (satisfactory clinical effect, decrease of CAS > or = 1) as compared to the pretreatment values after MP treatment (p < 0.05) and after 14 days of prednisone (p < 0.01). There were significant differences in sTNFR2 level after MP treatment (p < 0.02) and after corticosteroid administration (p < 0.05) between responders and non-responders. Baseline values of sTNFRI in GO individuals were positively correlated with CAS (r = 0.6, p < 0.02). CONCLUSIONS: TNFalpha acting through its receptors plays an important role in the pathogenesis of Graves' ophthalmopathy. Moreover, the beneficial influence of corticosteroids on the course of GO may be explained, at least in part, by an inhibition of sTNFR1 and sTNFR2. Measurement of soluble TNFalpha receptors might potentially serve as an indicator in prognostic estimation of corticosteroids' efficacy.

Adult↗
PubMed2004

Relationship between insulin sensitivity and sphingomyelin signaling pathway in human skeletal muscle.

In vitro studies revealed that insulin resistance might be associated with the intracellular formation of ceramide, the second messenger in the sphingomyelin signaling pathway. The aim of the present study was to examine the content and composition of fatty acids in ceramide and sphingomyelin in human muscle and to evaluate their relationships with insulin sensitivity. The study was conducted on 27 male subjects with normal glucose tolerance. Euglycemic-hyperinsulinemic clamps and biopsies of vastus lateralis muscle were performed. In 10 subjects, additional biopsies were taken after a 4-h clamp and after a clamp with concurrent Intralipid/heparin infusion. We identified 13 ceramides and sphingomyelins according to fatty acid residues. Insulin sensitivity was related to total ceramide content (r = -0.49, P = 0.01) and to ceramide consisting of palmitic (r = -0.48, P = 0.011), palmitoleic (r = -0.45, P = 0.019), mirystic (r = -0.42, P = 0.028), and nervonic acid (r = -0.39, P = 0.047). Hyperinsulinemia did not affect estimated muscle parameters. Intralipid/heparin infusion resulted in a 24.73% decrease in insulin sensitivity (P = 0.007) and a 47.81% increase in ceramide content (P = 0.005). These changes were significantly related to each other (r = -0.64, P = 0.046). A relationship with the decrease in insulin sensitivity was also observed for ceramides consisting of palmitic (r = -0.68, P = 0.03) and linoleic (r = -0.66, P = 0.038) acid. Our data indicate that the sphingomyelin signaling pathway in muscle might be an important factor determining the development of insulin resistance in humans.

Adult↗
PubMed2004

[Chronic complications in adult patients with newly diagnosed diabetes mellitus in relation to the presence of humoral autoimmune markers against pancreatic islet cells].

UNLABELLED: Latent autoimmune diabetes in adults (LADA) is subtype of diabetes type 1. It is well know, that 50% patients with new diagnosed diabetes type 2 present late complications. As far we don't know how many patients with new diagnosed diabetes have late complications according to presence of antibodies against islet antigens. The aim of the study was to compare late complications of diabetes: microangiopathy and macroangiopathy in newly diagnosed adult diabetic patients in relation to presence of humoral autoimmune markers. MATERIAL AND METHODS: We evaluated the presence of late complications in group of 41, hospitalized patients base on clinical examination and medical history. Glutaminic acid decarboxylase antibodies (anti-GAD), protein tyrosine phosphatase antibodies (anti-IA-2) and anti-insulin antibodies (IAA) titers were measured by RIA. The C peptide basal and stimulated, HbA1c, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, urea, creatinine levels and microalbuminuria were evaluated. RESULTS: The presence of islet cell specific antibodies were shown in 25 subjects. We observed late complications in 13/25 (52%) in group with positive antibodies titers, and in 10/16 (62.5%) in group without antibodies. We diagnosed the nephropathy (16% vs 6.25%), retinopathy (12% vs 0%), polyneuropathy (20% vs 12.5%), hypertension (32% vs 50%), chronic heart disease (8% vs 25%), overweight (32% vs 50%) and hyperlipidemia (12% vs 25%) respectively in subjects with and without antibodies. The concentrations of total cholesterol (185 +/- 47.8 vs 218 +/- 38.7, p < 0.05) and creatinine level (0.8 +/- 0.15 vs 0.95 +/- 24, p < 0.05) were higher in group without antibodies, but fasting glycemia (181 +/- 69.1 vs 132 +/- 32.8, p < 0.05) was higher in the group presenting with autoantibodies. We did not observed the difference between level of glycosylated hemoglobin in the investigated groups. RESULTS: There is the tendency to higher incidence of microangiopathy in group of patients positive to islet cell antibodies. Conversely the macroangiopathy appears frequently in patients without antibodies.

Adult↗
PubMed2004

[Serum Fas in patients with Graves' ophthalmopathy as a marker of activity of the ocular inflammatory infiltration].

UNLABELLED: Apoptosis plays an important role in the pathogenesis of autoimmune thyroid diseases. Soluble form of Fas (sFas) appeared as reliable markers of inflammation activity in rheumatic autoimmune diseases. The aim of the study was an estimation of sFas in patients with Graves' disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. MATERIAL AND METHODS: We detected serum Fas in three groups of subjects: 25 patients with clinical symptoms of ophthalmopathy (OG)(CAS > or = 4, anamnesis of OG > or = 1 yr), 18 patients with Graves' disease without ophthalmopathy (ChG) and 14 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone. The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of soluble Fas in the serum were determined by the ELISA and TSH receptor antibodies by RIA method. RESULTS: sFas concentration was significantly increased in patients with OG. We found a positive correlation between sFas and CAS and a negative correlation with duration of OG. During corticosteroid treatment there was no difference in sFas between responders and non-responders. CONCLUSIONS: sFas is a potent surrogate marker of inflammatory process activity in Graves' ophthalmopathy, however it has no prognostic value in the prediction of the immunotherapy efficacy.

Adult↗
PubMed2004

[Platelet-monocyte aggregate formation in patients with coronary heart disease and disorders of carbohydrate metabolism].

Circulating monocyte-platelet aggregates can release procoagulant, oxidative and mitogenic factors, thereby contributing to arterial thrombosis. The aim of our study was the estimation of heterophilic leukocyte-platelet aggregates in patients referred for coronary angiography, dependent on the degree of coronary stenosis and the disturbances of carbohydrate metabolism. Flow-cytometric analysis was performed in 50 consecutive patients with positive exercise test (age 54.2 +/- 6.4 years): 27 with normal glucose tolerance, 7 with impaired glucose tolerance and 16 with type 2 diabetes, and in 16 healthy subjects (age 44.8 +/- 14.1 years). We found that patients with coronary heart disease had increased leukocyte-platelet aggregate formation in comparison to the controls (the percentage of monocyte-platelet aggregates 47.5 +/- 23.0 vs 25.7 +/-12.8, p = 0.003, mean fluorescence intensity (MIF) 187.6 +/- 117.2 vs 79.3 +/- 42.8, p = 0.002, the percentage of granulocyte-platelet aggregates 20.7 +/- 10.4 vs 17.0 +/- 3.6, p = 0.009, MIF 64.2 +/- 41.3 vs 40.9 +/- 6.3, p = 0.008). The highest percentage of heterophilic aggregates was observed in patients with 1- and 2-vessel disease and those with "clean" vessels. In diabetic patients the percentage and MIF of granulocyte-platelet aggregates were decreased in comparison to the subjects with normal glucose tolerance (16.7 +/- 7.2 vs 22.8 +/- 9.8, p = 0.03 and 44.3 +/- 10.8 vs 74.4 +/- 48, p = 0.009, respectively). There was no increase in glycoprotein CD14 expression in any of the group studied. We found a positive correlation between the percentage of monocyte-platelet aggregates and fasting insulin level (r = 0.369, p = 0.04) and a negative correlation between MIF of monocyte-platelet aggregates and HDL level (r = -0.459, p = 0.012), between MIF CD14 and HDL level (r = -0.435, p = 0.02), and between the percentage of granulocyte-platelet aggregates and postprandial glycaemia (r = -0.4117, p = 0.03). We concluded that: 1. the patients with "clean" vessels represent a group of high atherothrombotic risk. 2. the patients with minimal coronary stenosis may benefit from anti-inflammatory and antiplatelet treatment.

Adult↗
PubMed2003

Plasma interleukin 8 concentrations in obese subjects with impaired glucose tolerance.

BACKGROUND: Interleukin 8 (IL-8) is a cytokine with atherogenic properties. In vitro studies revealed that it is produced and secreted by human adipocytes. We recently reported that plasma IL-8 is increased in obese subjects with normal glucose tolerance (NGT). The aim of the present study was to measure plasma IL-8 concentrations in subjects with impaired glucose tolerance (IGT). METHODS: A total of 44 subjects with marked overweight or obesity (BMI > 27.8 kg/m2), 27 with NGT and 17 with IGT, were recruited for the present study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test (OGTT) and after euglycemic hyperinsulinemic clamp. RESULTS: The studied groups did not differ in fasting IL-8 concentrations. Both OGTT and clamp resulted in a significant increase in plasma IL-8. The change in IL-8 after clamp was similar in both groups. In contrast, after OGTT plasma IL-8 levels (IL-8OGTT) were markedly higher in IGT individuals. In IGT, but not NGT group, IL-8OGTT was positively related to postload glucose and negatively to insulin sensitivity. CONCLUSION: Plasma IL-8 concentrations after glucose load are increased in obese IGT subjects in comparison to normoglycemic weight-matched individuals. Increase in plasma IL-8 might be both insulin-mediated (during clamp) and glucose-mediated (during OGTT).

Journal Article↗
PubMed2003

Interleukin 18 and transforming growth factor beta1 in the serum of patients with Graves' ophthalmopathy treated with corticosteroids.

Interleukin-18 (IL-18), a novel cytokine of the IL-1 family, and TGFbeta1 have been lately identified in several thyroid autoimmune diseases. The aim of this study was to estimate the influence of corticosteroids on serum IL-18 and TGFbeta1 in Graves' ophthalmopathy (GO) patients and to assess their potential as a guideline of immunosuppressive therapy. The study was carried out in three groups of subjects: (1). 17 patients with clinical symptoms of ophthalmopathy (GO) that underwent corticosteroid therapy consisting of intravenous methylprednisolone (MP) infusions and subsequent treatment with oral prednisone (P); (2). 14 patients with euthyroid Graves' disease (Gd) without symptoms of ophthalmopathy; (3). 12 healthy volunteers age- and sex-matched to groups 1 and 2. The serum levels of IL-18 and TGF beta1 were determined by the ELISA method. Thyroid receptor antibodies (TRAB) were estimated by the RIA method. Levels of IL-18 were significantly higher in both GO [340+/-109 pg/ml (p<0.02)] and Gd individuals [308+/-89 pg/ml (p<0.05)] as compared to the control group (238+/-88 pg/ml). There were no significant differences in TGFbeta1 concentrations between studied groups. TRAB values were significantly increased in both GO (p<0.001) and Gd individuals (p<0.001) as compared to the controls. In coticosteroid-responsive patients we have found a significant decrease in IL-18 serum concentration as compared to the pretreatment values. We did not find any correlation between IL-18 or TGFbeta1 and TRAB, duration of GO, clinical activity score (CAS) or proptosis. Our results suggest that efficient corticosteroid therapy in patients with Graves' ophthalmopathy may be related to its influence on systemic IL-18.

Adrenal Cortex Hormones↗
PubMed2003

Platelet sodium-proton exchanger and phospholipid-dependent procoagulant activity in patients with type 2 diabetes.

Platelet Na(+)/H(+) exchanger (NHE) activity, phospholipid-dependent thrombin generation, and platelet factor 3 (PF3) availability were measured in 83 type 2 diabetics and in 40 age- and sex-matched healthy subjects. Na(+)/H(+) exchanger activity was significantly increased in diabetic patients in comparison to the controls (kappa = 4.29 +/- 0.71 x 10(-3) x s(-1) v 3.21 +/- 0.64 x 10(-3) x s(-1), P <.00001). However, there was no significant difference between subjects with (kappa = 4.28 +/- 0.75 x 10(-3) x s(-1)) and without (kappa = 4.26 +/- 0.32 x10(-3) x s(-1)) arterial hypertension, as well as between patients with normo- and microalbuminuria or overt proteinuria (kappa = 4.26 +/- 0.58 x 10(-3) x s(-1), kappa = 4.47 +/- 0.93 x 10(-3) x s(-1) and kappa = 4.07 +/- 0.38 x10(-3) x s(-1), respectively). Comparatively high NHE activity was observed in the group of patients with hemoglobin A(1c) (HbA(1c)) less than 7.5%. Multiple regression analysis revealed that the factors independently related to platelet Na(+)/H(+) exchanger activity were: total PF3 activity (beta = 0.77, P =.011) and triglyceride (TG) concentration (beta = 0.44, P =.039). Phospholipid-dependent thrombin generation and PF3 availability were also enhanced in all plasma fractions of diabetic patients, especially in platelet-poor plasma (PPP) and platelet-free plasma (PFP) (P <.0001 and P <.00001, respectively). There was a positive correlation between NHE activity and thrombin generation, as well as with PF3 availability in all plasma fractions. Our results suggest that enhanced platelet Na(+)/H(+) exchanger activity associated with raised phospholipid-dependent procoagulant activity may increase the risk of vascular damage in type 2 diabetic patients.

Adult↗
PubMed2003

Intercellular adhesion molecule 1 gene polymorphisms in Graves' disease.

It was recently suggested that genetic factors could play a major role in the development of Graves' disease (GD). The aim of the present study was to evaluate the frequency of the c.721G-->A polymorphism and the c.1405A-->G polymorphism of the intercellular adhesion molecule 1 (ICAM-1) gene in subjects with GD compared with that in healthy controls, because ICAM-1 was found to play a key role in lymphocyte infiltration into the thyroid gland and the concentration of the soluble form of ICAM-1 correlates significantly with the clinical activity and treatment status in GD. We have analyzed the association of ICAM-1 polymorphisms with the age at onset of GD and the presence of ophthalmopathy. In a group of 235 patients with GD and 211 healthy controls we have shown that polymorphism at position c.721G-->A is associated with an earlier age of GD onset and that the c.1405A-->G polymorphism of the ICAM-1 gene could predispose to Graves' ophthalmopathy. This suggests that G241R and K469E amino acid substitutions in the ICAM-1 molecule could influence the intensity/duration of the autoimmunity process and the infiltration of orbital tissues. It could be speculated that therapy that modulates ICAM-1 function may delay the onset and/or prolong the remission and/or have an influence on clinical manifestations of GD.

Adolescent↗
PubMed2003

Soluble tumor necrosis factor-alpha receptors in young obese subjects with normal and impaired glucose tolerance.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a possible link between obesity and impaired glucose tolerance (IGT) and type 2 diabetes. Data about TNF-alpha and soluble forms of its receptors (sTNFR1 and sTNFR2) in IGT are controversial. The aim of the present study was to assess plasma TNF-alpha, sTNFR1, and sTNFR2 levels and to evaluate the relationships with insulin resistance in obese subjects with IGT. RESEARCH DESIGN AND METHODS: A total of 104 subjects participated in the present study: 30 obese subjects with IGT (obese-IGT), 32 obese subjects with normal glucose tolerance (obese-NGT), and 42 lean healthy control subjects (control-NGT). Anthropometry and blood biochemical parameters were measured and euglycemic-hyperinsulinemic clamp was performed. RESULTS: Obese-IGT subjects were more insulin resistant in comparison with obese-NGT and control-NGT groups; obese-NGT subjects were more insulin resistant than control-NGT. Plasma sTNFR1 and sTNFR2 were markedly higher in both groups of obese subjects in comparison with control-NGT and in the obese-IGT versus obese-NGT group. Plasma sTNFR1 and sTNFR2 were inversely related to insulin sensitivity. Both relationships remained significant after adjustment for age, BMI, waist girth, percent body fat, plasma glucose, insulin, nonesterified fatty acids, cholesterol, and triglycerides. Correlation between sTNFR2 and insulin sensitivity was also present in all the groups analyzed separately, but the correlation between sTNFR1 and insulin sensitivity was present only in the obese-NGT group. CONCLUSIONS: Our data suggest that TNF-alpha receptors are increased in obese-IGT subjects and are related to insulin resistance. These findings indicate that the TNF-alpha system might contribute to the development of insulin resistance in glucose-intolerant subjects.

Adult↗