The incidence of gestational diabetes mellitus before and after the introduction of HAPO diagnostic criteria.

INTRODUCTION: During the years 2014-2015 new diagnostic criteria for gestational diabetes mellitus (GDM) were gradually adopted by the Czech professional societies, which emerged from the results of the large prospective multicenter HAPO study (The Hyperglycemia and Adverse Pregnancy Outcome). The adoption of the new criteria was accompanied by concerns about the increase in the number of women with GDM. The paper deals with epidemiological results of GDM incidence in the first three years since the introduction of new criteria. METHODS AND RESULTS: In the years 2013-2014 GDM screening was performed at 1,594 pregnant woman at the General Teaching Hospital in Prague. According to that time valid diagnostic criteria (fasting glucose 5.6 mmol/g and/or 8.9 mmol/l in 60 min and/or 7.7 mmol/l in 120 min 75 g OGTT) GDM was found in 324, i.e. 20 % of women. In the years 2016-2018 were 2,629 pregnant women examined. GDM based on the new criteria (fasting blood glucose 5.1 mmol/l and/or 10 mmol/l in 60 min and/or 8.5 mmol/l in 120 min OGTT) was diagnosed in significantly less women - in 375, i.e. 14.3% (p < 0.0001). Overt diabetes, i.e. fasting glucose 7.0 mmol/l and/or 11.1 mmol/l in 120 min OGTT, was newly detected in 6 pregnant women, i.e. 0.2 %. Gestational diabetes was found in 62% cases based on repeated fasting fasting blood glucose and in 38% on the basis of higher blood glucose at 60 min and/or 120 min OGTT. GDM was significantly more prevalent in the age category over 30 years. Among women aged under 25 years GDM was present at 9.9%, aged 25-29.9 years at 9.6%, aged 30-34.9 years at 14.2% and aged 35 years at 18.6 %. Hypoglycaemia < 3.5 mmol/l experienced 2.9% of women during OGTT. When the screening in 2016-2018 was evaluated according to the previous diagnostic criteria, diabetes would be diagnosed in 16.2% of pregnant women. The result of the test would be falsely negative in 6% of all pregnant women, i.e. these women have repeatedly higher fasting glucose (5.1-5.5 mmol/l) according to the current criteria which was evaluated as physiological according to the previous criteria. However, in the HAPO, these values were already associated with a significant increase of complications. A total of 50% of women with GDM diagnosed according to the previous criteria would have a false positive result of OGTT (8.9-9.9 mmol/l in 60 min and/or 7.7-8.4 mmol/l in 120 min OGTT). These values are not considered to be significantly at risk under the new criteria. CONCLUSION: Our data do not confirm the increase in GDM incidence following the introduction of new diagnostic criteria which, according to current knowledge, better reflect the real risks of complications for the child and the mother. Applying the previous criteria has led to a number of false negative and positive results, so we consider the adoption of better-funded new criteria a step in the right direction. The incidence of diabetes was significant in all age categories and significantly increased in women over 30 years of age.

Pitfalls in screening for gestational diabetes in the Czech Republic - patient survey.

OBJECTIVE: The aim of our survey was to investigate gestational diabetes (GDM) screening policy in the Czech Republic with regards to the correct methodology of the screening. MATERIALS AND METHODS: 1100 anonymous questionnaires were distributed among patients of a tertiary level obstetric department from July 2015 to September 2015. RESULTS: 958 (87.0%) questionnaires were found eligible for analysis. 794 (82.9%) of participants had at least one risk factor for GDM development. The oGTT was performed in 751 (94.6%) women at risk of GDM and 153 (93.3%) women at low risk of GDM. From the 904 performed oGTT, 154 (17.0%) were performed completely by recommended standards. In the remaining cases, at least one deviation from standard was noted. The results of oGTT were provided by 364 (40.3%) of respondents. In this subgroup, 71 (19.5%) matched International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria for GDM diagnosis. However, these women were often not those who were evaluated as screening positive by the office gynaecologist. CONCLUSION: The screening for GDM was frequently not performed in accordance with the national guidelines and the diagnostic criteria used were not uniform.

[Why do we still hesitate to accept the new international criteria for the diagnosis of gestational diabetes mellitus? The current screening is non-uniform and does not correspond with evidence-based medicine]. / Proc stále váháme s prijetím nových mezinárodních kritérií pro diagnózu gestacního diabetes mellitus? Soucasný screening je nejednotný a neodpovídá medicíne zalozené na dukazech.

Gestational diabetes mellitus (GDM) is the most common internal complication in pregnancy and similarly as the frequency of Type 2 diabetes rises in general population so does the frequency of GDM. The causes include unhealthy life style, growing incidence of overweight and obesity as well as older age of pregnant women. Older data reported the frequency of GDM in 3-4% of all pregnancies in the Czech Republic, whereas nowadays its frequency with using the same diagnostic criteria is more than two times higher. If we include the measurement of glycemia in 1 hour of oGTT, the frequency of GDM reaches more than 20%. In case we accept the new recommendation of the International Association for Diabetes in Pregnancy Study Groups (IADPSG), it is expected that the frequency of GDM will be even higher. IADPSG recommendation resulted from HAPO study (Hyperglycemia and Adverse Pregnancy Outcomes), a large international observational study on the relationship between mild hyperglycemia and pregnancy outcomes. Adoption of these new criteria is intensively discussed among experts all over the world. WHO adopted the IADPSG criteria in 2013. The Czech Diabetes Society committee adopted them in April 2014. Any official statement about the new criteria has not yet been issued by the Czech Gynecology and Obstetrics Society. This article analyzes the old and the new diagnostic criteria, summarizes the most common arguments in favor and against the IADPSG thresholds and tries to open the discussion about this important topic.

[The alarming incidence of gestational diabetes mellitus using currently used and new international diagnostic criteria]. / Alarmující výskyt gestacního diabetes mellitus pri pouzití stávajících i nových mezinárodních diagnostických kritérií

OBJECTIVE: The aim of our study was to analyze the results of oral glucose tolerant test (oGTT) of pregnant woman with currently used Czech criteria for diagnosis of GDM, to find out the prevalence of GDM if the measurement of glycemia in 1 hour of oGTT is included and to compare the prevalence of GDM using the new IADPSG (International Association of Diabetes and Pregnancy Study Groups) criteria versus the currently used Czech criteria. DESIGN: Retrospective analysis. SETTINGS: Department of Obstetrics and Gynecology of the First Faculty of Medicine and General Teaching Hospital, Prague. METHODS: Data from the standard 75g 2-hour oral glucose tolerance test (oGTT) of 2567 pregnant females were analyzed using the currently recommended Czech cut-off values for plasma glucose at baseline and at2 hours of oGTT (5.6 and 7.7 mmol/l) and at baseline, 1 and2 hours oGTT (5.6, 8.9 and 7.7 mmol/l). The frequency of GDM using the Czech criteria was compared with the frequency of GDM using the novel IADPSG criteria (5.1, 10.0 and 8.5 mmol/l). Statistical analysis was done using the software GNU PSPP Statistical Analysis Software version 0.8.0-g0ad9f6. RESULTS: When using the current Czech criteria (at baseline and 2 hours of oGTT) GDM was diagnosed in 362 (14.11%) females. Inclusion of glycemia at 1 hour of oGTT increased the frequency of GDM to 571 (22.26%) females (p<0.00). With the novel IADPSG criteria GDM was diagnosed in 818 (31.89%) females (p=0.038). 503 females i.e. 19.61% and 394 females i.e. 15.36% (when glycemia at 1 h of oGTT included) respectively met the IADPSG but not the Czech criteria and thus were not treated for GDM. In contrast, 47 (1.83%) resp. 147 (5.73%) of tested women who met the Czech but not the IADPSG criteria received unnecessary diabetes treatment. CONCLUSION: The frequency of GDM is higher with the novel IADPSG criteria when compared with the currently used Czech recommendation. Switching to IADPSG criteria might help unravel hitherto unidentified cases of GDM and thus improve outcomes for females with GDM and their offsprings.

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

Steroids, steroid associated substances and gestational diabetes mellitus.

As gestational diabetes mellitus (GDM) is both a frequent and serious complication, steroid levels in pregnancy are extremely elevated and their role in pregnancy is crucial, this review focuses on the role of steroids and related substances in the GDM pathophysiology. Low SHBG levels are associated with insulin resistance and hyperinsulinemia, while also predicting a predisposition to GDM. Other relevant agents are placental hormones such as kisspeptin and CRH, playing also an important role beyond pregnancy, but which are synthesized here in smaller amounts in the hypothalamus. These hormones affect both the course of pregnancy as well as the synthesis of pregnancy steroids and may also be involved in the GDM pathophysiology. Steroids, whose biosynthesis is mainly provided by the fetal adrenal glands, placenta, maternal adrenal glands, and both maternal and fetal livers, are also synthesized in limited amounts directly in the pancreas and may influence the development of GDM. These substances involve the sulfated ?5 steroids primarily acting via modulating different ion channels and influencing the development of GDM in different directions, mostly diabetogenic progesterone and predominantly anti-diabetic estradiol acting both in genomic and non-genomic way, androgens associated with IR and hyperinsulinemia, neuroactive steroids affecting the pituitary functioning, and cortisol whose production is stimulated by CRH but which suppresses its pro-inflammatory effects. Due to the complex actions of steroids, studies assessing their predominant effect and studies assessing their predictive values for estimating predisposition to GDM are needed.

Serum adipocyte fatty acid binding protein levels in patients with type 2 diabetes mellitus and obesity: the influence of fenofibrate treatment.

Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-alpha agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-alpha agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6+/-2.1 microg/l, T2DM before F: 55.6+/-5.7 microg/l, T2DM after F: 54.2+/-5.4 microg/l, p 0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCR(glc)/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus.

Insulin-like growth factor axis in pregnancy and gestational diabetes mellitus.

The insulin-like growth factor (IGF) is involved in the regulation of growth and metabolism. The aim of this study was to determine selected parameters of IGF system at systemic and local levels [subcutaneous (SAT) and visceral adipose tissue (VAT)] to assess its possible role in gestational diabetes mellitus (GDM). 37 pregnant women (21 with GDM and 16 without GDM) and 15 age-matched non-pregnant females were included in the study. Blood samples were taken in 28-32 and 36-38 weeks of gestation and 6-12 months after delivery. SAT and VAT samples were obtained during delivery or surgery. Compared with non-pregnant women, serum IGF-1 and IGFBP-3 were increased in both groups of pregnant women. IGF-2 was elevated only in GDM women from 36 weeks of gestation culminating 6 months after delivery (p=0.003). Serum IGFBP-3 was increased and IGFBP-4 decreased in GDM women vs. pregnant women without GDM during the whole study (IGFBP-3: p?0.001 for GDM vs. non-GDM; IGFBP-4: p=0.004 for GDM vs. non-GDM). Pregnant women with GDM had decreased mRNA expression of IGF-1, IGF-1R and IGF-2R and IGFBP-4 in VAT and IGF-1R in SAT compared to pregnant women without GDM. Changes in local activity of IGF are associated with the development of GDM.

Changes in plasma concentrations and mRNA expression of hepatokines fetuin A, fetuin B and FGF21 in physiological pregnancy and gestational diabetes mellitus.

We measured plasma concentrations, adipose tissue and placental mRNA expression of hepatokines fetuin A, fetuin B and fibroblast growth factor 21 (FGF21) in 12 healthy pregnant women (P group), 12 pregnant women with gestational diabetes (GDM) and 10 healthy non-pregnant women (N group) to explore their potential role in the etiopathogenesis of GDM. GDM and P group had comparable BMI, C-reactive protein (CRP) and glycated hemoglobin levels while IL-10 and TNF-alpha levels were higher in GDM group. Fetuin A and fetuin B levels were higher in pregnancy as compared to N group and decreased after delivery with no apparent influence of GDM. In contrast, the pattern of changes of circulating FGF21 levels differed between GDM and P group. Fetuin A concentrations positively correlated with CRP, TNF-alpha mRNA expression in adipose tissue and IL-6 mRNA expression in placenta. Fetuin B positively correlated with CRP. FGF21 levels correlated positively with IFN-gamma mRNA in adipose tissue and inversely with IL-8 mRNA in the placenta. Taken together, fetuin A and fetuin B levels were increased during pregnancy regardless of the presence of GDM. In contrast, FGF21 patterns differed between healthy pregnant women and GDM patients suggesting a possible role of this hepatokine in the etiopathogenesis of GDM.

Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes.

PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.

[Pilot study to evaluate blood glucose control by a model predictive control algorithm with variable sampling rate vs. routine glucose management protocol in peri- and postoperative period in cardiac surgery patients]. / Pilotní studie pro srovnání pocítacového algoritmu s variabilním intervalem merení glykémie a standardního protokolu pro intenzivní inzulínovou terapii v peri- a pooperacním období u kardiochirurgických pacientu.

BACKGROUND: Increased blood glucose levels are frequently observed in critically ill patients. Recent studies have shown that the normalization of glycemia by intensive insulin therapy decreases mortality, length of the hospitalization and number of complications. METHODS AND RESULTS: The aim of this pilot study was to compare blood glucose control by an automated model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RP) in peri- and postoperative period in cardiac surgery patients. 20 patients were included into this study (14 men and 6 women, mean age 68 +/- 10 let, BMI 28.3 +/- 5.0 kg/m2). 10 patients were randomized for treatment using eMPC algorithm and 10 patients for routine protocol. All patients underwent elective cardiac surgery and were treated with continuous insulin infusion to maintain glycemia in target range 4.4-6.1 mmol/l. The study duration was 24 hours. Mean blood glucose was significantly lower in eMPC vs. RP group (5.80 +/- 0.45 vs. 7.23 +/- 0.84 mmol/l, p < 0.05). Percentage of time in target range was significantly higher in eMPC vs. RP group (67.6 +/- 8.7% vs. 27.6 +/- 15.8%, p < 0.05). Percentage of time above the target range was higher in RP vs. eMPC group. Average insulin infusion rate was higher in eMPC vs. RP group (4.18 +/- 1.19 vs. 3.24 +/- 1.43 IU/hour, p < 0.05). Average sampling interval was significantly shorter in eMPC vs. RP group (1.51 +/- 0.24 vs. 2.03 +/- 0.16 hour, p < 0.05). No severe hypoglycaemia in either group occurred during the study. CONCLUSIONS: The results of our pilot study suggest that eMPC algorithm is more effective in maintaining euglycemia in peri- and post-operative period in patients after cardiac surgery and comparably safe as compared to RP.

[The treatment of hyperglycaemia in critically ill patients: comparison of standard protocol and computer algorithm]. / Lécba hyperglykemie u kriticky nemocných pacientu: srovnání standardního protokolu a pocítacového algoritmu.

INTRODUCTION: Hyperglycemia is commonly observed in patients hospitalized on intensive care units. It is has been demonstrated that normalization of blood glucose level using intensive insulin therapy significantly improves prognosis of these patients. The aim of our study was comparison of standard protocol of intensive insulin therapy used on cardiac surgery ICU in General University Hospital in Prague and computer algorithm MPC (Model Predictive Control). PATIENTS AND METHODS: 20 patients with glycaemia higher than 6.7 mmol/l at the time of admission to ICU were included into the study, 10 subjects were randomized for standard treatment, 10 for treatment with MPC algorithm. Glycaemia was measured hourly during 48 hours, insulin infusion was rate was adjusted hourly in MPC algorithm or in 1-2 hours in standard protocol group. RESULTS: Blood glucose levels were in the target range significantly longer in MPC relative to standard protocol group (26.3 +/- 2.1 hrs vs 20.3 +/- 2.5 hrs). Mean blood glucose was also lower using MPC algorithm (6.47 +/- 0.11 vs 6.72 +/- 0.23 mmol/l). On the contrary the target range was established faster using standard protocol (8.9 +/- 1.2 vs 10.3 +/- 0.9 hrs), duration of hyperglycaemia was the same in both groups (7.3 +/- 1.9 in standard protocol vs 7.3 +/- 1.3 hrs in MPC algorithm). Average 48-hours insulin dose was higher in MPC than standard protocol group (230.2 +/- 38.8 vs 199.1 +/- 27.8 IU/48 hrs). 2 hypoglycaemic episodes occured in 2 patients in standard protocol group. CONCLUSIONS: Our results show that the use of MPC algorithm result in more effective blood glucose control in critically ill patients than standard protocol.

The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women.

The aim of our study was to determine whether adipocyte-derived hormones leptin, adiponectin and resistin contribute to the improvement of insulin sensitivity after very-low calorie diet (VLCD). Therefore, serum levels of these hormones were measured in fourteen obese females before and after three weeks VLCD and in seventeen age- and sex-matched healthy controls. Body mass index, HOMA index, serum insulin and leptin levels in obese women before VLCD were significantly higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA 10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml, leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and soluble leptin receptors levels were significantly lower in obese women before VLCD than in the control group. No differences were found in serum glucose and resistin levels between the obese group before VLCD and the control group. VLCD significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels and increased soluble leptin receptor levels. The changes in serum adiponectin and resistin levels in obese women after VLCD did not reach statistical significance. We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not. Therefore, other mechanisms rather than changes in the endocrine function of the adipose tissue are probably involved in the VLCD-induced improvement of insulin sensitivity.

[Monitoring of glucose concentration in critical patients, comparing arterial blood glucose concentrations and interstitial glucose concentration measured by microdialysis technique]. / Monitorování glykemie u kriticky nemocných pacientu: srovnání arteriálních a intersticiálníh hladin glukózy merených pomocí mikrodialýzy tukové tkáne.

INTRODUCTION: Recent studies have shown that normalization of blood glucose in critically ill patients by intensive insulin therapy significantly decreases their mortality and morbidity. The aim of our study was to compare interstitial glucose concentrations in subcutaneous adipose tissue (measured by microdialysis technique) and arterial blood glucose concentrations to test the suitability of subcutaneous adipose tissue for long-term placement of biosensors for glucose measurement in critically ill patients. PATIENTS AND METHODS: 20 patients (16 men and 4 women) after cardiac surgery hospitalized at postoperative intensive care unit were included into the study. Mean age was 68 +/- 10 years, BMI was 28.3 +/- 3.9 year. Only patients with glycemia higher than 6.7 mmol/l at a time of admission to the ICU were included. Samples for measurement of interstitial glucose concentrations were collected in 60 minutes intervals during 48 hours using microdialysis of the subcutaneous adipose tissue. Perfusion fluid was 5% mannitol, perfusion rate was 1 microl/min. Arterial blood glucose concentration was measured in 60 minutes intervals, absolute concentrations of interstitial glucose were calculated using ionic reference technique. RESULTS: Mean arterial glucose concentration during the study was 6.7 +/- 0.56 mmol/l, absolute concentration of glucose in interstitial fluid was 3.55 +/- 0.58 mmol/l. Mean correlation coefficient between arterial and interstitial concentrations was 0.77 +/- 0.15. CONCLUSION: Our study demonstrated good correlation between interstitial glucose concentrations in subcutaneous adipose tissue and arterial blood glucose concentrations in post-cardiac surgery patients. Further studies are needed to evaluate this relationship in patients with more severely disturbed perfusion of subcutaneous adipose tissue.

[Serum concentrations of adiponectin in patients with restrictive and purgative subtype of mental anorexia]. / Se'rové koncentrace adiponectinu u pacientek s restriktivním a purgativním podtypem mentální anorexie.

BACKGROUND: The aim of our study was to compare serum concentrations of adiponectin, leptin and other selected parameters in female patients with restrictive subtype of anorexia nervosa (n=15), (RMA), binge/purge subtype of anorexia nervosa (n=11) (PMA) with age-matched healthy females, (C, n=14). METHODS AND RESULTS: RMA patients had the most severely decreased body mass index (BMI) and serum leptin levels of the three groups studied. These parameters were also significantly lower in PMA relative to C group. (BMI: RMA 14.61 +/- 0.49 kg/m2, PMA 17.30 +/- 0.25 kg/m2, C 23.21 +/- 0.96 kg/m2; leptin: RMA 1.39 +/- 0.31 ng/ml, PMA 3.72 +/- 0.77 ng/ml, C 9.17 +/- 1.53 ng/ml). In contrast, serum adiponectin levels were markedly increased in RMA patients (57.28 +/- 4.86 ug/ml) relative to other groups (PMA 40,25 +/- 2.18 microg/ml, K 26.84 +/- 2.40 microg/ml). Serum leptin levels positively correlated with BMI in all groups studied (r = 0.56, p = 0.002), while the inverse relationship was found for adiponectin levels and BMI (r = -0.72, p = 0.000003). The hormonal concentrations were measured by commercially available RIA and ELISA kits. CONCLUSIONS: The most significant changes of serum adiponectin and leptin levels were found in the RMA group with most severely decreased BMI and body fat content relative to rest of the groups. Possible role of increased adiponectin levels in the etiopathogenesis and/or metabolic changes in patients with anorexia nervosa is under the scope of our current investigations.

Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum.

BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.