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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.

Graves’ orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p

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.

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and

Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention.The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 andlt;7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed.Women with GDM (Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

Gestational diabetes mellitus (GDM) represents a heterogeneous group of hyperglycemic metabolic disorders that are associated with health outcomes for mothers and offspring. Currently, diagnosis of GDM is based on repetitive measurement of increased fasting plasma glucose (FPG) or upon results showing increased postprandial plasma glucose (PPG). Recently, it was discovered that the changes in the gut microbiome during pregnancy are associated with insulin resistance and obesity. Therefore, in this study, relevant products of gut bacteria, short-chain fatty acids (SCFA) and their derivatives were evaluated together with baseline body composition characteristics and common biochemical parameters in women with three different phenotypes of GDM, healthy pregnant and nonpregnant women. Plasma SCFA and their derivatives were derivatized, separated on reversed-phase liquid chromatography and detected by a triple-quadrupole mass spectrometer. 3-hydroxybutyrate (3-OH-BA), 4-methylvalerate (4-MVA) and isovalerate (IVA), together with selected parameters associated with baseline body composition characteristics and biochemistry, were evaluated as statistically significant. 3-OH-BA, which was increased in all three groups of women with different phenotypes of GDM, reflects a ketogenic state of GDM. In all groups of pregnant women, elevated/suppressed concentrations of 4-MVA/IVA were found. These findings show the importance of monitoring SCFA and other parameters besides glucose in women with GDM.

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.

Coronary risk evaluation by conventional factors (age, gender, smoking, blood pressure and cholesterol) may further be specified by facets of the metabolic syndrome, namely insulin resistance, hypertriglyceridemia and obesity. Although obesity is usually defined as elevated body mass index (BMI), recent data indicate a superior role of waist circumference or hypertri-glyceridemic waist (HTGW) over BMI in the assessment of cardiometabolic risk. In dyslipidemic patients, the specific contributions of risky waist, HTGW or BMI have not been evaluated as yet. 686 dyslipidemic subjects (322 males and 364 females) were enrolled into a cross-sectional study. In each subject basic antropometry (i.e. waist circumference, HTGW, BMI) and laboratory parameters of lipid profile and insulin resistance were determined. Cardiometabolic risk was given by fulfilling the criteria (harmonized definition) of metabolic syndrome. The significance of risky waist, HTGW and BMI were assessed by comparing the respective predictive values for the presence of metabolic syndrome. Dyslipidemic patients with risky waist, HTGW or high BMI have a more atherogenic lipid profile and higher insulin resistance compared to those without risky waist, HTGW or high BMI. Risky waist is stronger predictor of metabolic syndrome (PPV 66 %, NPV 90 %) and thus posesa greater cardiometabolic risk than higher BMI per se does (PPV 42 %, NPV 97 %). The contribution of triglycerides (i.e. HTGW) to these predictive values is marginal (PPV 66 %, NPV 92 %). The present results highlight the superior role of waist circumference as a screening tool over BMI for the evaluation of cardiometabolic risk in dyslipidemic subjects. HTGW brings little additional benefit in risk stratification. Lower BMI proved to be optimal for identifying the subjects with inferior risk.

We report a new variant in the LDLRAP1 gene associated with autosomal recessive hypercholesterolemia in a woman of central European ancestry.

To compare circulating pigment epithelium derived factor (PEDF) levels in type 2 diabetes patients (T2D) with and without metabolic syndrome (MetS+/-) to healthy controls and assess PEDF association with plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) as markers of endothelial dysfunction. Fifty T2D individuals and forty healthy controls were included. PEDF, PAI-1, vWF, anthropological parameters, lipids, and markers of insulin resistance were investigated in all subjects. Compared to controls only MetS+ diabetics had higher PEDF levels [14.2 (10.2-16.0) mg/l vs. 11.1 (8.6-14.4) mg/l; p

Background: To evaluate the association between hypertriglyceridemic waist (HTGW), a promising marker of visceral adiposity and cardiovascular (CV) risk, and different indicators of vascular damage...

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.

Background and aim Diabetes mellitus is a very common metabolic disease with a rising incidence. It is one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. Adipocytokines, synthetized by adipose tissue influence metabolic pathways and disorders in various ways. In this review article, we chose the most researched adipocytokines and evaluated their relationship to posttransplant diabetes mellitus. The aim of this paper is to summarize current knowledge and discuss their perspective role in diagnostics or therapy of the new onset diabetes mellitus after transplantation.

In this study we compared levels of selected adipokines between patients with type 2 diabetes (T2D) and healthy individuals and we determined their relationship with early vascular damage markers.Seventy-seven subjects: 56 patients with T2D (34 men and 22 women) and 21 healthy controls (8 men and 13 women) were examined in this cross-sectional study. Selected adipokines [adiponectin, adipocyte fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF-21), C1q/TNF-related protein 9 (CTRP-9), and allograft inflammatory factor-1 (AIF-1)] with possible cardiovascular impact were measured in all participants. To identify markers of vascular damage von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and arterial stiffness parameters were examined in all the subjects.When compared with healthy controls, T2D had significantly higher levels of A-FABP [50.0 (38.1-68.6) vs. 28.6 (23.6-32.9) ng/mL, P 0.0001] and lower levels of adiponectin [5.9 (4.3-9.0) vs. 11.3 (8.7-14.8) μg/mL, P 0.0001]. Differences in other adipokines were not statistically significant. Adiponectin level correlated negatively with vWF levels (ρ = -0.29, P 0.05) and PAI-1 (ρ = -0.36, P 0.05) and A-FABP positively with vWF (ρ = 0.61, P 0.05) and PAI-1 (ρ = 0.47, P 0.05) and augmentation index (ρ = 0.26, P 0.05). Multivariate regression analysis showed independent association between A-FABP and vWF (b = 0.24, P 0.05).Patients with T2D have significantly higher levels of A-FABP and lower levels of adiponectin. These adipokines correlate with indicators of vascular damage and could contribute to cardiovascular risk in patients with T2D. A-FABP may participate in direct endothelium damage.

BackgroundLow level of cardiorespiratory fitness has been recognized as an important independent and modifiable risk factor of increased morbidity and mortality. However, in standard outpatient settings, patients are not routinely screened for fitness and advantages of such testing for the management of type 2 diabetes have not been defined.AimTo describe the toleration of a fast, simple and practicable fitness test (2-min step-in-place test) by overweight/obese type 2 diabetics and their performance indicated by 2-min step-in-place test score (STS). To study short-term anthropometric, functional and metabolic changes following the implementation of the test in the selected population.MethodsA total of 33 overweight/obese type 2 diabetics underwent, besides routine examination at the outpatient clinic, the fitness test (group A). Patients were asked to increase their regular physical activity with focus on walking without change in diet and chronic medication. Three to four months later, the subjects were tested again. An identical number of age- and sex-matched obese diabetics followed in our outpatient clinic (without fitness testing), was randomly selected from the Hospital Information System (control group B).FindingsAll patients subjected to fitness testing completed the protocol successfully. STS score was found to have a considerable range with differences between males and females at the borderline of statistical significance. The data are compliant with lower aerobic endurance of obese diabetics compared with healthy population. Within study period, the tested group presented with improvements in STS (referring especially to the males) as well as in several laboratory parameters of glucose and lipid homeostasis, glomerular function and subclinical inflammation with no reflection in anthropometry. Group B demonstrated no significant change. In conclusion, 2-min step-in-place test is fast, undemanding and well-tolerated by patients and personnel. Following its validation based on cardiopulmonary exercise testing, the test may prove recommendable for screening or self-monitoring purposes.

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.

Endokrinni nebo take Graves-Basedowova orbitopatie (EO) je zavažna, progresivni ocni komplikace asociovana s autoimunitnim onemocněnim stitne žlazy. Typickými přiznaky jsou retrakce horniho vicka, periorbitalni edem, porucha pohyblivosti ocniho bulbu, diplopie, zanětlivý otok měkkých tkani orbity vedouci k protruzi oka a ve važnějsich připadech až ztrata zraku v důsledku utlaku zrakoveho nervu ci poskozeni rohovky. Standardem lecby je kortikoterapie, podani per os je limitovano nežadoucimi ucinky, proto je upřednostňovano podani v podobě intravenozniho pulzu. V roce 2016 bylo vydano jednotne doporuceni European Thyroid Association a European Group on Graves´ Orbithopaty (EUGOGO) pro endokrinni orbitopatii a take doporuceni American Thyroid Association pro lecbu hypertyreozy, ktere zahrnuje lecbu EO.

K lecbě recidivujicich symptomatických cyst stitne žlazy, kde je prosta evakuace neuspěsna, lze s výhodou využit sklerotizaciabsolutnim alkoholem pod ultrasonografickou kontrolou (US-PEIT). Metoda je vhodna u nemocných, kteři maji zvýsene operacniriziko. Take ji lze použit u pacientů, kteři se nechtěji podrobit operacnimu výkonu. Terapeutický uspěch v publikovanýchsouborech se pohybuje mezi 68 až 100 %. Podle Medical Guidelines for Clinical Practice for the Diagnosis and Management ofThyroid Nodules byla US-PEIT schvalena jak v USA, tak v Evropě v roce 2010 jako plnohodnotna alternativa chirurgickeho řeseni.

Cardiovascular (CV) disease is the primary cause of death in diabetic patients and one of the explanations may be increased arterial stiffness. Arterial stiffness assessment using pulse wave analysis, is a predictive factor of CV events. The aim of this paper is to review the current knowledge of relations between diabetes mellitus and pulse wave analysis. A MEDLINE search was performed to retrieve both original and review articles addressing the relations and influences on arterial stiffness in diabetics. Pulse wave analysis is considered as a gold standard in CV risk evaluation for patients at risk, especially diabetics. Arterial stiffness assessment may be helpful for choosing more aggressive diagnostic and therapeutic strategies, particularly in younger patients to reduce the incidence of CV disease in these patients.

Hyperuricemia has been described as associated with the risk of development metabolic syndrome; however the relationship between the uric acid level and particular parameters of metabolic syndrome remained unclear. We performed a cross-sectional study on a cohort of 833 dyslipidemic patients and correlated their levels of uric acid with parameters of insulin resistance, lipid metabolism, C-reactive protein, anthropometric parameters. We also defined patients with hypertriglyceridemic waist phenotype and compered their uric acid levels with those without this phenotype. We found that levels of uric acid are associated with parameters of metabolic syndrome. Specifically, dyslipidemia characteristic for metabolic syndrome (low HDL cholesterol and high triglycerides) correlates better with uric acid levels than parameters of insulin resistance. Also waist circumference correlates better with uric acid levels than body mass index. Patients with hypertriglyceridemic waist phenotype had higher levels of uric acid when compared with patients without this phenotype. Serum uric acid levels are even in low levels linearly correlated with parameters of metabolic syndrome (better with typical lipid characteristics than with parameters of insulin resistance) and could be associated with higher cardiovascular risk.

Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mean age 45.6±14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

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.

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.

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.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.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.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.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.

INTRODUCTION: Thyroid tissue ectopically located in the ovary can be reported accidentally after adnexectomy, but as a primary cause of hyperthyroidism this diagnosis is rare. The clinical search for a functional ectopic thyroid tissue requires intense clinical focus and a multidisciplinary approach. CASE DESCRIPTION: This case report demonstrates a patient with a history of Graves’ disease who had undergone thyroidectomy combined with postoperative (131)I radioablation. Despite the previous treatment, she developed an outburst of hyperthyroidism ten years later. Only very close follow-up enabled us to disclose the right condition. The ovarian source of thyroid hormone production was removed by laparoscopic adnexectomy and a right sided benign ovarian struma was confirmed. CONCLUSION: Most patients treated by thyroidectomy and radioiodine do not require extended periods of follow-up or postoperative investigations, but when the clinical or laboratory signs change, clinicians should be prepared to perform the necessary re-evaluation in order to provide the best care.

With the increasing prevalence of obesity and especially abdominal obesity, a simple clinical tool is needed that identifies the cardiometabolic risk for cardiovascular disease and type 2 diabetes. The aim of our study was to evaluate a broad spectrum of metabolic variables and IMT in subjects with and without hypertriglyceridemic waist (HTGW) and compare it with the harmonized definition of metabolic syndrome (MS) with both a higher (MS-I) and lower waist circumference (MS-II) for Europids. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women) into our cross-sectional study. The subjects with HTGW had an atherogenic lipid profile (significantly higher triglycerides, AIP, non-HDL-C, lower HDL-C and ApoA-1, and the women also higher TC and ApoB), increased markers of insulin resistance (insulin, HOMA, C-peptide, proinsulin), inflammation (hsCRP), thrombosis (fibrinogen, PAI-1), SBP and DBP, and lower adiponectin (p