Type 1 diabetes and coronary artery disease.
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Coronary Artery Disease↗
Biomedical subjects
Adam Kretowski
Publications and source records attributed to Adam Kretowski.
Susceptibility to type 1 diabetes is associated with ApoCIII gene haplotypes.
Type 1 diabetes is a disease of beta-cell destruction leading to insulin deficiency. Genes for type 1 diabetes have been identified; however, much of the genetic risk remains unexplained. Genetic variation within the apolipoprotein CIII (apoCIII) gene alters apoCIII levels, which are increased in type 1 diabetes and induce beta-cell apoptosis. We therefore hypothesize haplotypes within the apoCIII gene are associated with type 1 diabetes. DNA from 584 type 1 diabetic patients and 591 control subjects were genotyped for six single nucleotide polymorphisms (SNPs) in the apoCIII gene (C-641A, C-482T, T-455C, C1100T, C3175G, and T3206G). Two alleles of a haplotype block (promoter SNPs + C3175G) were associated with type 1 diabetes. The A-T-C-C allele frequency was higher in type 1 diabetes (0.19 vs. 0.16, P = 0.05), and the C-C-T-C allele was reduced in type 1 diabetes (0.60 vs. 0.65, P = 0.04). The odds ratio (OR) for A-T-C-C allele increased with 0, 1, and 2 copies (OR of 1.00, 1.24, and 1.60, respectively; P = 0.05) and decreased for the C-C-T-C allele (1.00, 0.97, and 0.73, respectively; P = 0.03). This haplotype block contains an insulin response element. Screening for this haplotype may identify at-risk individuals, and this pathway may offer a target for prevention of type 1 diabetes.
Adult↗
[Current views on the etiopathogenesis of goiter in children].
The most frequent cause of goiter in children is a deficit of iodine, leading to endemia of goiter in the regions with insufficient supplementation of this element. Goiter occurs also in the course of autoimmunological diseases of the thyroid gland (Hashimoto disease, Graves' disease), genetically-related disorders of thyroid hormones, biosynthesis/impaired biosynthesis of thyroid hormones. According to the theory of goiter pathogenesis, excessive enlargement of the thyroid gland is due to adaptation of follicle cells of the gland aiming at neutralizing the impaired synthesis of the thyroid hormones caused by various intrathyroid, environmental and genetic factors/agents. The mechanisms stimulating thyrocytes to hyperplasia or hypertrophy are very complex and still unknown in spite of having identified many physiological and pathogenetic factors connected with goiter.
Child↗
[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↗
[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↗
[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↗
[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↗
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↗
[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↗
Serum levels of interleukin-18--a potential marker of cardiovascular death--could be determined by genetic predisposition.
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Angina Pectoris↗
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↗
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↗
Interleukin-18 promoter polymorphisms in type 1 diabetes.
Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of gamma-interferon production. The aim of our study was to evaluate the frequency of known polymorphisms in the IL-18 promoter in patients with type 1 diabetes in comparison with healthy control subjects, since higher levels of IL-18 were recently reported in the subclinical stage of type 1 diabetes. We studied two recently described single-nucleotide polymorphisms of the promoter of IL-18 gene at the position -137 and -607, which have been suggested to cause differences in transcription factor binding and have an impact on IL-18 gene activity. The genotype distribution differed significantly between patients with type 1 diabetes and control subjects. The difference reflected an increase in the GC genotypes and a decrease in GG genotypes at position -137 in the promoter of IL-18 gene. AA genotype at position -607 was found only in the control group. The results also demonstrated that the contribution of -137GC genotypes to genetic susceptibility to type 1 diabetes differs depending on the combination of IL-18 promotor gene haplotypes. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the promoter of IL-18 gene.
Base Sequence↗
Thyrotropin receptor antibodies detected by the human recombinant TBII assay--a surrogate marker for autoimmune activity in Graves' ophthalmopathy?
BACKGROUND: Recently a new very sensitive and specific commercial method for detection of TSHR-Ab has become available: TBII assay using human recombinant TSHR. The aim of this study was to assess the potential of this novel TBII assay as a guideline for immunosuppressive therapy in patients with Graves' ophthalmopathy (GO). MATERIAL/METHODS: We detected serum TBII level in three groups of subjects: 17 patients with clinical symptoms of GO, 14 patients with Graves' disease without ophthalmopathy (Gd), and 13 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone (P). Serum samples were collected 24 hours before MP, 24 hours after MP, after 14 days of P treatment and after the end of corticosteroid therapy. RESULTS: The levels of TBII were significantly increased in both GO and Gd individuals as compared to the controls (p<0.001 and p<0.01 respectively). There was also a significant difference in serum TBII between GO and Gd patients (p<0.01). We observed elevated pretreatment TBII serum levels in corticosteroid-resistant individuals as compared to corticosteroid- responsive patients. Corticosteroids caused a significant decrease in TBII serum levels in GO patients. CONCLUSIONS: The lack of clinical improvement despite decreased TBII level in our study suggests that the humoral immune response is not crucial in the pathogenesis of early GO. However, measurement of TSHR-Ab by the novel h-TBII assay may have prognostic value in the treatment of patients with severe GO as a surrogate marker of autoimmune activity.
Adrenal Cortex Hormones↗
[Pathophysiology and etiopathogenesis of gestational diabetes mellitus].
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Blood Glucose↗
[The influence of corticosteroids on IL-6/IL-6R system in patients with Graves' ophthalmopathy].
UNLABELLED: IL-6 and its soluble receptor (IL-6R) appeared as reliable markers of inflammation activity in autoimmune diseases. The aim of the study was an estimation of serum IL-6 and sIL-R in patients with Graves' disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. We detected serum HIL-6 and IL-6R in three groups of subjects: 18 patients with clinical symptoms of ophthalmopathy (Clinical Activity Score > or = 3, 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 soluble IL-6 and IL-6R in the serum were determined by the ELISA method (Quantikine kit, R&D Systems, Minneapolis). The statistical significance was estimated by the Mann-Whitney U-test. IL-6 concentration was significantly increased in patients with GO in comparison to the controls (12.4 +/- 3.7 vs 11.8 +/- 3.2; p < 0.05). After MP treatment in corticosteroid-responsive patients (improvement in CAS < or = 1) serum concentration of sIL-6R decreased significantly in comparison to pretreatment values (32.8 +/- 4.2 vs 28.6 +/- 4.9; p < 0.05). We found a positive correlation between IL-6 concentration and degree of proptosis. CONCLUSIONS: 1. IL-6/IL-6R system plays an important role in the pathogenesis of GO. 2. IL-6R is a potent prognostic factor for efficacy of the immunotherapy but further investigations are needed.
Adult↗
[Postpartum evaluation of amylin secretion in gestational diabetes mellitus].
Amylin (Islet Amyloid Pancreatic Polypeptide - IAPP) is a hormone cosecreted with insulin by pancreatic beta cells in a pulsatile pattern. Recent reports point to its essential part in glucose homeostasis. Postpartum evaluation of IAPP release in Gestational Diabetes Mellitus (GDM) patients was performed. Our data were compared to insulin and peptide-C secretion patterns. We were not able to demonstrate a dynamic increase of IAPP in response to glucagon stimuli. However, related to GDM, puerperal IAPP levels were significantly higher than in normal controls. Lack of postpartum amylin response to glucagon stimulation might be interpreted as a primary result of previously reported increases in circulatory levels of IAPP during pregnancy complicated by GDM. Post partum elevated IAPP may be a useful marker to identify patients with high risk of type 2 diabetes mellitus.
Adult↗
[Postpartum maternal plasma leptin levels and their relationship to gestational diabetes mellitus].
UNLABELLED: Leptin is a protein hormone mainly produced by the adipocytes. Apart from its autocrine role within the placenta in humans, plasma circulating leptin contributes to the endocrine function. Leptin levels may serve as an index of metabolic and energy balance in pregnancy. Recent reports have shown a positive correlation between leptin concentrations and plasma levels of glycated haemoglobin (HbA(1c)) in patients with gestational diabetes mellitus (GDM). OBJECTIVES: The aim of the present study was to evaluate leptin levels after delivery in GDM and normal glucose tolerance (NGT) women. MATERIALS AND METHODS: Plasma leptin concentration and insulin, c-peptide and glycated haemoglobin were measured in both. NGT women and in patients with a history of GDM in all patients total LDL - and HDL cholesterol concentrations were estimated. We also calculated the anthropometric parameters of the mother and birth weight in both groups. RESULTS: The plasma leptin concentration after delivery was not different in patients with GDM in comparison with the NGT individuals. CONCLUSIONS: We concluded that in patients with GDM and normal BM1 the postpartum leptin level was not different in comparison with the NGT patients.
Adult↗