Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.

Ocular hypertension in patients with active thyroid-associated orbitopathy: a predictor of disease severity, particularly of extraocular muscle enlargement.

The purpose was to ascertain if any relation exists between the elevated intraocular pressure (IOP) in patients with thyroid-associated orbitopathy (TAO) in active stage and the severity of extraocular muscle involvement and the extent of exophthalmos. METHODS: A total of 96 eyes and orbits of 48 adult patients with active TAO were investigated. All patients underwent magnetic resonance imaging of the orbit and measurement of all extraocular recti muscles (EOM). The obtained data was divided into two groups according to the IOP value: normal IOP ≤ 21 mmHg; n = 47 and elevated IOP with IOP > 21 mmHg; n = 49, and analyszed. RESULTS: A significant difference was found in the short diameter of medial rectus and inferior rectus muscles and in the sum of short parameters of all EOM. All these parameters were significantly higher in the elevated IOP group. Motility restriction in at least one gaze direction was also significantly more frequent (p < 0.0001) in the elevated IOP group. A positive moderate correlation was found between IOP and the sum of short parameters of EOM (r = 0.496). No correlation was found between the IOP and exophthalmos values (r = 0.267). During the follow-up, the frequency of strabismus surgery and orbital decompression was significantly higher in the elevated IOP group (p = 0.003; p = 0.002). CONCLUSION: Elevated IOP in the active TAO stage particularly correlates with extraocular muscle involvement. These patients are also more likely to require orbital decompression and strabismus surgery.

Oral semaglutide - Rybelsus®, the first GLP-1 receptor agonist for oral use in clinical practice.

Glucagon like peptide-1 receptor agonists (GLP-1 RA) are potent antidiabetic drugs associated with significant weight loss and minimal risk of hypoglycemia. Semaglutide is a GLP-1 RA with a proven cardiovascular benefit. It is currently also available in oral form, which is especially suitable for the treatment of the initial phase of type 2 diabetes. However, it is also effective at later initiation of therapy, in different diabetic populations. The PIONEER 6 trial demonstrated cardiovascular safety of oral semaglutide, its administration was accompanied by a significant reduction in cardiovascular and overall mortality.

Role of Adipose Tissue in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.

Biologic therapy for dyslipidemia.

Dyslipidemia treatment represents a very dynamically growing segment of pharmacotherapy, including a production of biological agents. Nowadays, they are targeting at various proteins that are involved in the synthesis, transport, or metabolism of lipoproteins. This review provides a statement of current options for the biological treatment of dyslipidemias and for other products that have the potential to broaden its spectrum in the near future.

Circulating levels of selected adipokines in women with gestational diabetes and type 2 diabetes.

BACKGROUNDS: Adiponectin, adipocyte-fatty acid binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines closely associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation to metabolic parameters. METHODS: Women with GDM, T2DM and healthy women were included in this cross-sectional study. In addition to adipokines, anthropometric, lipid parameters, markers of insulin resistance and glucose control were assessed in all participants. RESULTS: Compared to healthy controls (n = 35) significantly lower levels of adiponectin were detected in women with GDM (n = 50), whereas in women with T2DM (n = 50) higher levels of A-FABP and WISP-1 and lower levels of adiponectin were found. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. A-FABP and adiponectin were independently associated with levels of triglycerides, HDL-cholesterol and C-peptide insulin resistance index. WISP-1 correlated only with waist circumference. CONCLUSIONS: Adverse adipokines production reflecting dysfunctional fat tissue is less presented in women with GDM than in women with T2DM, but more expressed compared to healthy women.

Atherosclerosis in patients with type 1 diabetes.

Type 1 diabetes is often associated with the early manifestation of atherosclerosis, which represents the morphological basis for macrovascular complications of diabetics. Atherosclerosis in patients with type 1 diabetes shows certain specific features that result from different proportions of risk factors, the presence of diabetes and its complications. The paper deals with the possibilities of influencing and detecting the atherosclerotic process in these risk patients.

Pioglitazone.

Pioglitazone belongs to the drugs primarily reducing insulin resistance. Currently, it is the only insulin sensitizer available. In addition to hypoglycaemic action, it has a number of other metabolically beneficial effects that are responsible for its positive effect on the vascular wall. The paper provides an overview of cardiovascular clinical trials with pioglitazone, its safety profile and practical recommendations for its administration.

Differential diagnosis of hypoglycemia.

Our review summarizes the possible differential diagnoses of hypoglycemia. It confirms the absolute necessity of fulfilling all the three Whipple hypoglycemia criteria. Briefly is mentioned Clinical symptoms of hypoglycemia are briefly mentioned and several ways to classify the hypoglycemic events are offered. Highlighted is the recommended approach to distinguish patients as seemingly ill and healthy and also as hypoglycemia occurring in diabetic and non-diabetic. All the classifications and recommendations are summarized in attached tables and schemes.

Can Visceral Adiposity Index Serve as a Simple Tool for Identifying Individuals with Insulin Resistance in Daily Clinical Practice?

Background and objectives: The visceral adiposity index (VAI), estimating visceral adiposity dysfunction through a simple formula, could serve as a useful tool for identifying individuals at higher cardiometabolic risk. Its relationship with insulin resistance (IR), assessed using the homeostasis model assessment of IR (HOMA-IR), and metabolic syndrome (MetS) components remains unclear. The study aimed to investigate the association of VAI with both HOMA-IR and MetS. Materials and Methods: After undergoing anthropometric and biochemical studies, 783 individuals were divided into three groups according to a number of present MetS components. The VAI cut-offs signaling MetS and HOMA-IR were determined by maximizing the sum of the sensitivity and specificity. Correlation analysis was performed to explore the associations between VAI and other tested parameters. A logistic stepwise regression analysis was applied to identify statistically significant determinants of HOMA-IR. Given the variability of reference values, two thresholds of HOMA-IR were applied, namely 2.0 and 3.8. Results: VAI increased significantly between the groups with a rising number of MetS components. The VAI cut-off for MetS was 2.37, with a sensitivity of 0.86 and a specificity of 0.78. The same cut-off point identified subjects with HOMA-IR = 3.8, with a sensitivity of 0.79 and a specificity of 0.66. The VAI cut-off for HOMA-IR = 2.0 was 1.89, with a sensitivity of 0.74 and a specificity of 0.68. The strongest correlations of VAI were noted with HOMA-IR (r = 0.51) and insulin (r = 0.49), respectively, while the strongest correlation of HOMA-IR was with waist circumference (r = 0.54). Not one of the routine parameters was a significant predictor in the regression analysis. Conclusions: The obtained results show an existing association of VAI with HOMA-IR. The high sensitivity and specificity of the cut-offs may allow the application of VAI in common clinical practice.

Combined lipid-lowering therapy.

Dyslipidemia belongs to the main risk factors for atherosclerosis. To achieve current blood lipid targets, it is often necessary to use intensive hypolipidemic therapy including a combination of individual hypolipidemic drugs. In terms of cardiovascular risk reduction, it is important that the patient is treated with the highest tolerated dose of statin. In the next step, we decide to co-administer ezetimibe and/or fibrate, and for high-risk patients an additional treatment with proprotein convertase subtilisin kexin 9 inhibitors should be considered. The manuscript provides an overview of the individual combinations effectiveness to influence lipid spectrum and the incidence of cardiovascular diseases. Key words: cardiovascular disease - dyslipidemia - ezetimibe - fibrates - PCSK9 inhibitors - statins.

A summary of the EAS consensus concerning the causal relationship between low-density lipoproteins and atherosclerotic cardiovascular diseases, prepared by the Board of the Czech Society for Atherosclerosis.

This article summarised opinion of the European Society for Atherosclerosis on the causal relationship between low density lipoprotein (LDL) and the development of atherosclerosis. The fact that there is a clear causal relationship between the LDL concentration and the development of atherosclerotic cardiovascular disease (ASKVO) is evidenced by congenital lipid metabolism disorders and results of prospective epidemiological studies, Mendelian randomized trials, and randomized controlled trials. It is documented that the effect of LDL exposure on ASKVO development is cumulative; the additive effect of other risk factors is also discussed. In conclusion the facts, underlying the rational approach to the therapy of patients with dyslipidemia, are summarized. Key words: atherosclerotic cardiovascular disease - LDL - low density lipoprotein - EAS.

RETROSPECTIVE ANALYSIS OF PATIENTS WITH GRAVES ORBITOPATHY TREATED BY PULSES OF METHYLPREDNISOLONE, WITH A FOCUS ON ADVERSE EVENTS.

OBJECTIVE: Graves orbitopathy (GO) is an extrathyroidal manifestation of autoimmune thyroid disease. Early treatment with glucocorticoids in appropriately selected patients is recommended for active, moderate to severe, and sight-threatening disease. The recently published European Group on Graves Orbitopathy guidelines re-evaluated the recommended doses of intravenous methylprednisolone (ivMP) in response to the potential for adverse effects. We retrospectively reviewed our patient cohort treated with our ivMP protocol and analyzed the side effects of this treatment when given during hospitalization in our tertiary referral center. METHODS: Between May 2007 and May 2017, a total of 171 consecutive patients with active, moderate to severe, or sight-threatening GO were treated with ivMP in a cumulative dose of 7.5 grams, given monthly in three hospital sessions. Adverse events were reported using Version 4 of Common Terminology Criteria for Adverse Events. RESULTS: Ninety-two percent of patients who started the treatment were able to finish it; 5% did not finish the study due to adverse events, and 3% did not finish the treatment protocol because of noncompliance. The most common adverse events were asymptomatic changes in laboratory values (liver enzymes), psychiatric disorders, and infectious complications. None of the patients in the study died during the ivMP treatment, including those patients who experienced adverse effects or discontinued the protocol because of noncompliance. CONCLUSION: High-dose ivMP for active, moderate to severe, and sight-threatening GO, when applied cautiously in carefully selected and monitored patients, is generally safe during the treatment period. ABBREVIATIONS: AE = adverse effect; CAS = clinical activity score; CTCAE = Common Terminology Criteria for Adverse Events; DM = diabetes mellitus; EUGOGO = European Group on Graves Orbitopathy; GC = glucocorticoid; GO = Graves orbitopathy; ivMP = intravenous methylprednisolone.

[Diabetic dyslipidemia and microvascular complications of diabetes]. / Diabetická dyslipidemie a mikrovaskulární komplikace diabetu.

Diabetic dyslipidemia is one of the main risk factors for atherosclerosis. Although its participation in diabetic microvascular complications is not that dominant, dyslipidemia may play an important role in formation and progression of these complications. Pathophysiological mechanisms by which diabetic dyslipidemia affects the etiopathogenesis of diabetic nephropathy, retinopathy, neuropathy and diabetic foot are presented. The data from clinical studies and treatment possibilities for particular microvascular complications using lipid-lowering therapy are discussed.Key words: diabetes mellitus - diabetic foot - dyslipidemia - nephropathy - neuropathy - retinopathy.

[Familial combined hyperlipidemia - the most common genetic dyslipidemia in population and in patients with premature atherothrombotic cardiovascular disease]. / Familiární kombinovaná hyperlipidemie - nejcastejsí familiární dyslipidemie v bezné populaci i u pacientu s casným výskytem aterotrombotických kardiovaskulárních príhod.

Familial combined hyperlipidemia (FCH) is the most frequent genetic dyslipidemia (DLP) with high risk of early atherosclerosis manifestation. It is characterized by elevated both triglycerides 1.5 mmol/l and apolipoprotein B 1.2 g/l (hyper-TG/hyper-ApoB fenotype), with at least two affected family members. Despite the fact that plasmatic levels of total cholesterol and LDL-C are usually lower than in familial hypercholesterolemia and full expression of DLP in FCH occurs in adulthood, risk of premature manifestation of atherosclerosis is similar in both these familial DLP. It is probably due to the presence of other atherogenic lipid and non-lipid risk factors, such as increased levels of triglyceride rich lipoprotein remnants, presence of small dense LDL, reduction of HDL-C, presence of insulin resistance with impaired glucose homeostasis, hepatic steatosis, arterial hypertension, hyperuricemia and presence of increased markers of systemic inflammation. The term "familial" usually implicates a monogenic trait. However, FCH is almost always nonmendelian. According to recent knowledge FCH is mostly polygenic with variable presence of large effect mutations, accumulation of several small-effect polymorphisms and some environmental influences. Therefore, FCH is rather a syndrome with common clinical presentation but multigenic causes. The term "familial combined hyperlipidemia" is embedded in clinical practice and so it is not necessary to abandon it, as it nearly urges to examination of first degree relatives. This might help to identify a great number of risk subjects who deserve appropriate management.Key words: apolipoprotein B - familial combined hyperlipidemia - genetics - insulin resistance - premature atherosclerosis - triglycerides.

[The effect of antidiabetic treatment on the bone of patients with type 2 diabetes]. / Vliv antidiabetické lécby na skelet nemocných s diabetes mellitus 2. typu.

UNLABELLED: Despite a normal or higher bone mass, type 2 diabetes is associated with a higher risk of osteoporotic fractures. Besides a higher falls frequency the lower quality of diabetics bone plays the crucial role in this case. One of the factors affecting their fracture risk is a choice of antidiabetic treatment. So far, professional societies have warned before the thiazolidinediones use only, but gliflozines can be harmful for bone too. Metformin, sulfonylureas, GLP-1 agonists and DPP-4 inhibitors belong to the drugs without a negative effect on the fracture risk. The increased frequency of bone fractures in diabetics treated with insulin lies more in the fact that these patients suffer from diabetes longer, have more diabetic complications and are at a higher risk of hypoglycemia, which is associated with a higher frequency of falls. In individuals with a high fracture risk antidiabetic drugs without a negative effect on bones should be recommended. KEY WORDS: DPP-4 inhibitors - gliflozines - GLP-1 agonists - insulin - metformin - osteoporosis - sulfonylureas - thiazolidinediones - type 2 diabetes mellitus.

[Uric acid as a risk factor for cardiovascular diseases]. / Kyselina mocová jako rizikový faktor kardiovaskulárních onemocnení.

According to current knowledge, uric acid plays an important role in pathogenesis of civilizational diseases - obesity, metabolic syndrome and cardiovascular diseases. Uric acid has become an independent risk factor of morbidity and mortality. It is questionable, if the relationship between uric acid and cardiovascular diseases is direct (through influence on endothelial dysfunction, oxidative stress and inflammation) or indirect (mediated by known risk factors of cardiovascular diseases - metabolic syndrome, obesity, insulin resistance and hypertension). This article describes relationship between particular cardiovascular risk factors and uric acid. However, on the basis of current knowledge it is not possible to recommend treatment of hyperuricemia in order to decrease cardiovascular risk.Key words: fructose - insulin resistance - metabolic syndrome - uric acid - visceral obesity.

[Hypoglycemia as a symptom of cancer in adults]. / Hypoglykemie jako symptom maligního onemocnení v dospelém veku.

UNLABELLED: Decrease of blood glucose levels below 3 mmol/l is in fully developed cases accompanied by neuroglycopenic symptoms that may even lead to altered state of consciousness. The treating physician frequently faces a complicated situation. This may be due to inappropriately administered drugs including cases motivated by self-harm intentions (insulin, insulin secretagogues), or alcohol abuse. Undernourished people, or those afflicted with a serious systemic infection, end-stage liver or kidney diseases or with a failing heart, belong to a risk group. Hypoglycemia typically accompanies hypocorticism (Addisons disease) or lack of glucagon. Endogenous hyperinsulinism caused by a hormonally active pancreatic cancer, that is, by a neuroendocrine tumour - insulinoma, is a possibility to be considered. A hidden cause of hypoglycemias may be a pancreatic-beta- cell dysfunction (nesidioblastosis, or non-insulin pancreatogenous hypoglycemia). A similar situation may arise following gastric bypass surgery. Hypoglycemia incited by the presence of antibodies to insulin or its receptor is cited in literature as a very rare problem. One section in the differentially diagnostic thinking is dedicated to hypoglycemic states accompanying neoplastic, malign processes. Insulin is demonstrably not a responsible agent here, it is a polypeptide structurally close to it, a somatomedin abbreviated as IGF2. KEY WORDS: endoscopic ultrasound pancreatography (EUPG) - hypoglycemia mediated by tumour cells other than ß cells (NIPHS) - insulin-like growth factor (IGF1, IGF2) - pro-insulin-like growth factor IGF2 (pro-IGF2).

[Endocrine orbitopathy - the topic still alive]. / Endokrinní orbitopatie - téma stále zivé.

Endocrine orbitopathy (EO) must be understood mainly as a result of oxidative stress. The pathological process finally affects both the appearance and vision of the patient. In the case of inappropriate or late treatment or lack of patient cooperation, it significantly influences the quality of life of those affected. In spite of the sophisticated dia-gnostic algorithms, in some cases it is difficult to confirm the diagnosis of EO. The range of laboratory methods, the essential part of the diagnostic process, has only recently been extended by the possibility of quantification of specific, stimulating immunoglobulins (TSI). A major shortcoming may be seen in an undervalued importance of orbital ultrasonography, in particular of the eye muscles (US).Key words: biological treatment - endocrine orbitopathy (EO) - Graves-Basedow disease (GB) - "hashitoxicosis" (HTX) - hyaluronan synthase 2 (HAS2) - thyroid-blocking immunoglobulins (TBI) - thyroid-stimulating immunoglobulins (TSI) - hyaluronic acid (HA) - lymphocytary, Hashimotos thyroiditis (HT) - pulse therapy - TSH-receptor - transcription factors FOXOs - orbital ultrasonography, mainly of the eye muscles (US).

Fasting Plasma Glucose and Its Relationship to Anthropometric Phenotype in Women Diagnosed with Gestational Diabetes According to IADPSG Criteria.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by new-onset hyperglycemia in pregnancy. According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations, GDM may be diagnosed based on repeatedly increased fasting glucose levels in the first trimester, or later, the detection of increased fasting glucose and/or increased glucose levels during a 75 g oral glucose tolerance test (OGTT). The study aimed to assess whether differences may be found between women diagnosed with GDM by fasting glucose or glucose challenge tests in early or late pregnancy. METHODS: The retrospective observational study enrolled 418 women diagnosed with GDM in accordance with the IADPSG criteria: early pregnancy fasting plasma glucose (FPG) ≥ 5.1 mmol/L; late pregnancy FPG ≥ 5.1 mmol/L (0 min) and/or postprandial plasma glucose (PPG) ≥ 10.0 mmol/L (60 min), PPG ≥ 8.5 mmol/L (120 min) 75 g OGTT. The analyses included anthropometric parameters at the beginning and during pregnancy, laboratory values of glycated hemoglobin, fructosamine, birth weight measures and the presence of neonatal complications. RESULTS: There were significant differences in body weight (78.3 ± 19.1; 74.0 ± 16.7; 67.2 ± 15.7 kg) and body mass index (BMI) (27.9 ± 6.6; 26.4 ± 5.8; 24.4 ± 5.2 kg/m2) in early pregnancy. Differences were also found in gestational weight gain (9.3 ± 6.8 vs. 12.4 ± 6.9 vs. 11.1 ± 4.7 kg) and the need for insulin therapy (14.7%; 7.1%; 4.0%). The study revealed no difference in the presence of neonatal complications but differences in birth weight (3372.2 ± 552.2 vs. 3415.6 ± 529.0 vs. 3199.0 ± 560.5 g). CONCLUSIONS: Gestational diabetes, characterized by FPG ≥ 5.1 mmol/L in early pregnancy, is associated with higher body weight and BMI at the beginning of pregnancy as well as with a higher risk for insulin therapy and increased birth weight.