The influence of incretin mimetics on cardiovascular risk factors in diabetes.

The authors discuss the strategy of use of incretin hormones in type 2 diabetes treatment in the context of cardiovascular complications. The results of the phase III study on human GLP-1 (Glucagon-like peptide-1) analogue-liraglutide have been presented under common acronym LEAD (Liraglutide-Effect and Action In Diabetes). The liraglutide therapy improved glycemic control with low hypoglycemia risk and decreased glycated hemoglobin by an average 1,13%. Decreases in systolic pressure and significant body weight loss were observed. Not only did the index describing beta cells function HOMA-B improve but also did the ratio of insulin to proinsulin. Summing up, incretin hormones beneficially influence blood glucose level, moreover, their use decreases blood pressure and body weight which might indicate their positive influence on cardiovascular system in diabetic patients.

Serum soluble glycoprotein 130 concentration is inversely related to insulin sensitivity in women with polycystic ovary syndrome.

OBJECTIVE: Insulin resistance might play a role in the pathogenesis of polycystic ovarian syndrome (PCOS). The family of glycoprotein 130 (gp130) cytokines could influence insulin action. One of these cytokines is interleukin (IL)-6, which exerts a short-term insulin-sensitizing effect, whereas in a long-term period, it might induce insulin resistance. Some other gp130 activators are supposed to have beneficial metabolic effects. Gp130 is present in the circulation in the soluble form (sgp130), which inhibits intracellular gp130 signaling. The aim of the present study was to estimate the relation between sgp130 and insulin sensitivity in women with PCOS. RESEARCH DESIGN AND METHODS: We studied 78 women with PCOS (35 lean and 43 obese) and 34 healthy women (18 lean and 16 obese). The euglycemic-hyperinsulinemic clamp and the measurements of serum sgp130, IL-6, soluble IL-6 receptor (sIL-6R), and sex hormones were performed. RESULTS: Both obesity and PCOS were characterized by an increased sgp130 (P < 0.0001 and P = 0.0002, respectively). sIL-6R concentration was lower (P = 0.0036) in women with PCOS independently of obesity. Serum sgp130 was negatively correlated with insulin sensitivity when control and PCOS women were analyzed together (r = -0.36, P < 0.0001) and in the PCOS subjects separately (r = -0.34, P = 0.002). In multiple regression analysis, this correlation was significant after adjustment for BMI, waist, percent of body fat, postload glucose and insulin, triglycerides, and high-sensitive C-reactive protein. CONCLUSIONS: Serum sgp130 is inversely and independently associated with insulin sensitivity in women with PCOS. An increased serum sgp130 in obesity and PCOS suggests an inhibition of intracellular gp130 signaling in insulin-resistant conditions.

Insulin resistance, serum adiponectin, and proinflammatory markers in young subjects with the metabolic syndrome.

Insulin resistance is the underlying metabolic abnormality in the metabolic syndrome. The low-grade chronic inflammation may be associated with metabolic risk factors and atherogenesis. The aim of our study was to establish the link between the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) criteria, and insulin sensitivity, serum adiponectin, and parameters of chronic inflammation in young subjects. The group of 223 subjects (mean age, 25.86 +/- 5.49 years; body mass index, 28.04 +/- 6.91 kg/m2) was studied. Oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and estimation of serum adiponectin and proinflammatory factors were performed. The NCEP-defined metabolic syndrome was present in 49 subjects (21.97%). The higher the number of NCEP criteria fulfilled was, the bigger were the decrease in insulin sensitivity (P < .0001) and adiponectin (P < .0001) and the increase in fasting and postload insulin (both Ps < .0001), C-reactive protein (P < .0001), interleukin 18 (P < .0001), interleukin 6 (P < .0001), and soluble tumor necrosis factor-alpha receptors sTNFR1 (P < .0001) and sTNFR2 (P < .0001) observed. Multiple regression analysis revealed that adiponectin and inflammatory factors predicted NCEP score independent of insulin sensitivity (all adjusted beta values between .16 and .32, all Ps < .01). Young subjects with metabolic syndrome demonstrate an increased inflammatory response and lower adiponectin concentration.

Glycosaminoglycans urinary excretion as a marker of the early stages of diabetic nephropathy and the disease progression.

BACKGROUND: Diabetes mellitus affects the metabolism of several components of extra-cellular matrix, including glycosaminoglycans (GAG). Alterations in the metabolism of GAG may play an important role in the development of diabetic complications. METHODS: Consequently, the relationship between diabetic nephropathy and urinary GAG excretion has been estimated in 86 diabetic patients (33 type 1 diabetes mellitus (DM), 53 type 2 DM) in comparison to 30 healthy controls (Figure 1). GAG concentration in 24-h urine samples has been determined by precipitation with cetylpyridinum chloride and potassium acetate in ethanol followed by a fluorometric test with 2-Hexadecyl-9H-pyrido(4,3b)indolium Bromide. RESULTS: Diabetic subjects excrete significantly more GAG than the control group (66.47 mg/24 h vs 50.11 mg/24 h). A marked difference in urinary GAG excretion between diabetic patients with nephropathy (74.66 +/- 7.5 mg/24 h) and without nephropathy (50.13 +/- 5.37 mg/24 h) has been detected. With diabetic nephropathy, patients with a longer history of GAG excretion experience an increase. An increased urinary GAG excretion has been detected in patients with microalbuminuria or macroalbuminuria. CONCLUSIONS: In conclusion, it can be stated that all patients with DM compared to the control group show an increase in GAG excretion independent of diabetes duration. Urinary GAG excretion positively correlates with the duration of diabetic nephropathy. The assessment of GAG excretion values may be useful for determining the early stages of diabetic nephropathy and the progression of the disease.

[Glucokinase gene mutations in gestational diabetes in Polish population. Prediction of diabetes mellitus development after delivery]. / Mutacje genu glukokinazy w cukrzycy ciezarnych w populacji polskiej. Prognozowanie ryzyka rozwoju cukrzycy po ciazy.

Gestational Diabetes Mellitus (GDM) comprises different forms of glucose metabolism disturbances with first recognition during pregnancy. There are a number of publications that have suggested that diabetes with onset during pregnancy is not a monogeneous disease and apart from "classical" form of GDM, which precedes type 2 diabetes development, MODY 2 diabetes, caused by monogenic defect of glucokinase gene, is relatively frequent "subtype" of gestational diabetes. The aim of our study was to estimate the risk of diabetes mellitus development, including MODY 2 diabetes, between 6 months - 10 years after delivery in 225 women with gestational diabetes. Gucokinase gene mutations and polymorphisms were performed by direct sequencing of DNA. In the present study it was shown that the frequency of glucokinase gene mutation is 6.7% in the Polish population of gestational diabetic women and 17.8% of new onset or persistant diabetes recognised during 5 years after pregnancy could be a result of this mutation. We have also observed that risk of type 2 diabetes development is about 50% in the next 5 years after delivery in women with gestational diabetes and is associated with higher levels of BMI during or after delivery and with clinical and biochemical features of insulin resistance (high values of WHR abd HOMA-R). Moreover, our study suggests that c.1253+8 C-->T polymorphism in intron 9 of glucokinase gene could have a role in predisposition to type 2 diabetes in women with gestational diabetes. In summary, our results suggest that, because of high costs and time-consuming methods of genetic studies, the investigations of glucokinase gene mutations should be concentrated in women with gestational diabetes without clinical and biochemical features of insulin resistance, but with family history of diabetes in two generations.

[Tumor necrosis factor-alpha system in patients with gestational diabetes]. / Aktywnosc ukladu czynnika martwicy guzów alfa (TNF-alpha) u pacjentek z cukrzyca ciazowa.

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.

[Evaluation of influence of selenium, copper, zinc and iron concentrations on thyroid gland size in school children with normal ioduria]. / Ocena zaleznosci miedzy stezeniem selenu, miedzi, cynku oraz zelaza w surowicy krwi a wielkoscia tarczycy u dzieci szkolnych z prawidlowym wydalaniem jodu w moczu.

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 Bialystok 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.

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.

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.

[Prevalence of autoimmunological disorders of the thyroid in children in the Bialystok population]. / Ocena wysteipowania zaburzen autoimmunologicznych tarczycy u dzieci w populacji bialegostoku.

Up-to-date observations in the regions where effective food iodine supplementation was introduced confirm a significant decrease in goiter incidence. However, in some regions the incidence of goiter remains unchanged or even the increase in the frequency of autoimmunological diseases of the thyroid like, Grave's-Basedov disease and chronic/subacute lymphocytic thyroiditis is observed. The purpose of the study was to evaluate the prevalence of autoimmunological diseases of the thyroid in children aged 6-13 years in the Polish population after 5 years of obligatory iodine supplementation program. The study included 480 school children from 4 elementary schools chosen randomly in the city of Bialystok and 120 patients at the same age treated due to goiter with KI and/or thyroxin for minimum 12 months in the Regional Specialist Outpatient 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 Sandell-Költhoff. The concentrations ofTSH and antibodies against TSH, thyroid-peroxidase (TPO) and thyroglobulin (Tg) were also determined. The mean concentrations of anti-Tg antibodies were statistically significantly higher in children with goiter in comparison with children with the thyroid gland within the norm (155.8 IU/ml vs. 24.4 IU/ml, p = 0.045). In children with goiter the incidence of'positive' titre of anti-Tg antibodies was 4-fold as high as in children without goiter (33.3% vs. 8.7%, p = 0.0147). High incidence of antibodies against thyroglobulin in the population of children with goiter and a positive correlation between the titre of anti-Tg antibodies and the size of the thyroid in this group suggest a significant role of autoimmunological disorders in the pathogenesis of goiter in the studied population.

[Obesity as a risk factor of chronic kidney disease in patients undergoing primary angioplasty]. / Otylosc jako czynnik ryzyka przewleklej choroby nerek u pacjentów z prawidlowym styzeniem kreatyniny poddawanych pierwotnej angioplastyce.

The number of patients with chronic kidney disease-CKD is still growing. Overweight and obesity present also an important problem of world public health. However, there are not many data showing possible association between obesity and incresing risk of development of renal failure recently it has been demonstrated that in obese patients secondary focal segmental glomerulosclerosis and glomerular hypertrophy appear more frequently. The aim of this study was to estimate glomerular filtration rate-GFR in patients with normal serum creatinine concentration undergoing primary angioplasty according to body mass index. The study included 1413 patients udergoing primary angioplasty for acute myocardial infarction. The following parameters were assessed: age, gender, family history of cardiovascular disease, risk factors of cardiovascular disease (hypertension, diabetes mellitus, obesity etc.), previous myocardial infarction, pre-existing heart failure, treatment given, localization of infarct, coronary stenting, serum creatinine before angioplasty, cholesterol, LDL, HDL, triglycerides, glucose, blood pressure. Of a total of 1413 patients, 1337 (94.62%, 943 M, 394 F) had correct serum creatinine concentration (below 1.5 mg/dl for men, below 1.2 mg/dl for women). Glomerular filtration rate was calculated from serum creatinine levels by using the simplified Modification of Diet in Renal Disease Study formula--MDRD, Cockcroft-Gault equation and Jeliffe formula. An average value of GFR in study group was 79.94 +/- 24.51 ml/min (Cockcroft-Gault equation), 73.02 +/- 21.96 ml/min (Cockcroft-Gault adjusted to weight), 90.37 +/- 25.1 ml/min (MDRD equation) and 77.67 +/- 21.65 ml/min (Jeliffe formula). A significant lower serum creatinine levels and GFR (assessed by 3 formulas and Cockcroft-Gault using adjusted weight) were observed in women group. In the whole study group (with normal serum creatinine levels) substantial correlation was found between age and serum creatinine concentration (r = 0.13, p > 0.001), GFR (MDRD, r = -0.37, p < 0.001, Cockcroft-Gault, r = -0.62, p < 0.001, adjusted to weight r = -0.64, p < 0.001, Jeliffe r = -0.61, p < 0.001) and also between BMI and GFR (MDRD r = 0.28, p < 0.001, Cockcroft-Gault, r = 0.31, p < 0.001, adjusted to weight r = 0.08, p < 0.001, Jeliffe r = 0.341, p < 0.001), but not with serum creatinine concentration (r = 0.03, p = 0.3). In patients with normal serum creatinine levels percentage of patients with GFR below 60 ml/min ranges from 4.79% up to 30.74%. In patients with higher BMI, higher GFR may be partially caused by glomerular hyperfiltration. Overweight or obesity are significant, but potentially changeable risk factors for development of chronic renal failure. However, chronic kidney disease is one of the complications of obesity.

[The level of IGF-1 and TGF-beta-1 in the blood serum and the thyroid size in children with normal ioduria]. / Stezenie IGF-1 i TGFbeta-1 w surowicy krwi a wielkosc tarczycy u dzieci z prawidlowym wydalaniem jodu w moczu.

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 Bialystok 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.

[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]. / Ocena wielkosci tarczycy w populacji dzieci szkolnych w wieku 6-13 lat z prawidlowym wydalaniem jodu z moczem a przydatnosc stosowanych dotychczas wartosci referencyjnych.

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 Bialystok 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 Bialystok. 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.

[Chronic complications in adult patients with newly diagnosed diabetes mellitus in relation to the presence of humoral autoimmune markers against pancreatic islet cells]. / Wystepowanie przewleklych powiklan cukrzycy w grupie doroslych pacjentów ze swiezo rozpoznana cukrzyca w zaleznosci od obecnosci przeciwcial przeciwko antygenom wysp trzustkowych.

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.

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.

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.

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.

[Postpartum maternal plasma leptin levels and their relationship to gestational diabetes mellitus]. / Poporodowa ocena sekrecji leptyny u kobiet z rozpoznana cukrzyca ciezarnych.

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.

[Serum Fas in patients with Graves' ophthalmopathy as a marker of activity of the ocular inflammatory infiltration]. / Stezenie Fas w surowicy chorych z oftalmopatia w przebiegu choroby Gravesa-Basedowa jako wskaznik aktywnosci procesu zapalno-naciekowego oczodolów.

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.

[Platelet-monocyte aggregate formation in patients with coronary heart disease and disorders of carbohydrate metabolism]. / Krazace kompleksy plytkowo-monocytarne u pacjentów z choroba niedokrwienna serca i zaburzeniami metabolizmu weglowodanów.

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.