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.

Ethanol ablation of thyroid cysts in the young with a focus on efficacy and quality of life.

Objective: Ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) is used in patients with recurrent symptomatic thyroid cysts as a credible alternative to surgery. Young patients commonly do not wish to undergo surgery and prefer ethanol ablation, if available. The effect of this approach on quality of life is an essential factor in deciding on the treatment options, especially in the young with a long life expectancy and no comorbidity. Methods: We performed US-PEIT in a cohort of young patients, 15-30 years, from 2015 to 2020. The patients' general quality of life (QoL), self-reported compression symptoms and neck appearance were evaluated. Results: The cohort comprised 59 patients with 63 cysts, more women than men, with a mean age of 23.8 years. About 1.5 mL of injected alcohol were needed to reach a 90.7% mean cyst volume reduction ratio in 12 months. The method did not fail in any of the patients; a single US-PEIT session was undertaken in 46% of them. The procedure significantly improved each of the patients' symptoms with a significant total score difference (P < 0.001). The total symptom score correlated with the initial cyst volume (P = 0.002; r = 0.395). The mean QoL score by SF-36 6 months after the last US-PEIT was significantly different for physical component summary 56.5 (P < 0.001) but not different for mental component summary 47.7 (P = 0.125), compared to age-corresponding norms. Conclusions: US-PEIT is a safe and effective method for the young, leading to improvements in cosmetic and subjective complaints, and should also be considered as first-line treatment in the young.

Vascular Damage and Glycometabolic Control in Older Patients with Type 2 Diabetes.

Diabetes is one of the main risk factors for vascular damage, including endothelial dysfunction and arterial stiffness. The aim of this study was to compare selected parameters of vascular damage in patients with type 2 diabetes (T2D) in different age categories and to determine their relationship to indicators of glycometabolic control. A total of 160 patients with T2D were included in this cross-sectional study. They were divided into four age quartiles (with mean ages of 42.1 ± 4.5, 51.6 ± 1.4, 59.2 ± 3.0, and 69.8 ± 3.8, respectively). All subjects were evaluated for indicators of glycometabolic control and for arterial stiffness parameters along with markers of endothelial damage-tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). The oldest compared to the youngest participants showed significantly increased parameters of arterial stiffness (augmentation pressure 13.4 ± 8.6 vs. 6.7 ± 4.4 mm Hg, augmentation index 26.2 ± 11.3 vs. 19.6 ± 9.2 mm Hg, aortic pulse pressure 47.7 ± 17.1 vs. 33.7 ± 10.4 mm Hg, and pulse wave velocity 11.9 (10.1-14.3) vs. 8.2 (7.7-9.8) m/s) despite having similar glycometabolic control. Arterial stiffness parameters were mainly associated with age and blood pressure. Age and systolic blood pressure were major determinants of arterial stiffness regardless of glycometabolic control. The oldest patients also had the highest levels of vWF (153.7 ± 51.9 vs. 121.7 ± 42.5 %) but the lowest levels of PAI-1 (81.8 ± 47.5 vs. 90.0 ± 44.9 ng/mL). Markers of endothelial dysfunction correlated with metabolic parameters, but did not correlate with arterial stiffness. Age and systolic blood pressure are major determinants of arterial stiffness in patients with T2D regardless of glycometabolic control, whereas an unfavorable metabolic profile is mainly related to endothelial dysfunction. These results suggest a differential contribution of cardiometabolic risk factors to vascular damage in T2D patients over their lifetime.

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.

Non-altered incretin secretion in women with impaired fasting plasma glucose in the early stage of pregnancy: a case control study.

BACKGROUNDS: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. METHODS: This study was undertaken as a case-control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and < 7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n = 22). Age-matched controls consisted of healthy pregnant (n = 25) and non-pregnant (n = 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). RESULTS: Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose [GLP-1AUC 19.0 (53.1) and GIPAUC 302 (100) pg/mL/min] and healthy pregnant women [GLP-1AUC 16.7 (22.3) and GIPAUC 297 (142) pg/mL/min] or non-pregnant controls [GLP-1AUC 16.8 (9.8) and for GIPAUC 313 (98) pg/mL/min]. Although women with impaired fasting glucose were more obese and showed decreased beta-cell function, there were not significant correlations between incretin production and parameters of insulin secretion, insulin resistance, or obesity. CONCLUSIONS: Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM.

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.

Specific gut bacterial and fungal microbiota pattern in the first half of pregnancy is linked to the development of gestational diabetes mellitus in the cohort including obese women.

Aims: Gestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development. Methods: We collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA). Results: We found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM. Conclusions: We conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.

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.

Adiponectin, A-FABP and FGF-19 Levels in Women with Early Diagnosed Gestational Diabetes.

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 <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. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: 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.

Adipocytokines in Graves' orbitopathy and the effect of high-dose corticosteroids.

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 < 0.0001). AIF-1 was significantly associated with the presence of GO after adjusting for clinical factors (age, sex, smoking and BMI) and level of TSH (odds ratio 1.003, p < 0.01). This finding could enforce targeting macrophages in treatment strategies for GO since AIF-1 is considered as a marker of their activation.

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.

Hypertriglyceridemic Waist in Patients with Type 2 Diabetes: Its Relationship to Selected Markers of Vascular Damage.

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 in type 2 diabetes (T2D) patients. Methods: This case-control study included 161 patients with T2D (91 males, 70 females) and 40 healthy controls (24 males, 16 females). HTWG was defined as waist circumference >90 cm in men or >85 cm in women and triglyceride concentrations >2 mmol/L. In addition to anthropometric and metabolic parameters, markers of endothelial dysfunction, namely von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1), were assessed. Arterial stiffness parameters were examined using the SphygmoCor system. Results: Individuals with T2D and HTGW showed the highest elevation of PAI-1 levels and significantly increased vWF levels compared with healthy controls. No significant differences in arterial stiffness markers were observed between T2D individuals. Age and, for several markers, systolic and/or diastolic blood pressure were identified as the main predictors for arterial stiffness, whereas PAI-1 and vWF levels were predicted by metabolic parameters. Conclusions: HTGW represents increased CV risk in T2D patients, mainly due to endothelial damage. The presence of HTGW had no significant effect on arterial stiffness compared with other T2D individuals.

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.

Changes in serum lipid levels during pregnancy in women with gestational diabetes. A narrative review.

We review current knowledge on lipid metabolism changes during pregnancy with special focus on changes in gestational diabetes. In physiological pregnancy, total plasma cholesterol, triglyceride and HDL-cholesterol level rises, the atherogenic index (LDL-cholesterol / HDL-cholesterol remains unchanged. Compared with healthy women, women with GDM show more pronounced signs of mixed dyslipidaemia - increased levels of triglyceride, changes in cholesterol and lipoprotein concentrations with a shift towards greater small dense LDL subtractions, which is typical for insulin resistance states. Dyslipidaemia, particularly hypertriglyceridemia, is thought to be one of the key drivers of foetal macrosomia and that is why measurements of plasma lipids may be valuable in detecting the metabolic abnormality in GDM and in predicting foetal outcome. Dyslipidaemia in GDM is seen as proatherogenic and potentially harmful for the baby and therefore it should be monitored more carefully.

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.

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.

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.

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.

Safe and effective percutaneous ethanol injection therapy of 200 thyroid cysts.

INTRODUCTION: Ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) is a minimally invasive procedure that may be performed as an alternative to surgery for the treatment of recurrent symptomatic thyroid cysts for which simple aspiration failed. The present study aimed at assessing US-PEIT in a large cohort of patients, identifying factors influencing treatment outcome. METHODS: Retrospective analysis of 193 patients with 200 thyroid cysts who underwent US-PEIT in 2004-2018. RESULTS: The initial median cyst volume was 8.5 mL [5.5-16.0]; median final volume at 12 months after the completion of therapy was 0.5 mL [0.2-1.3]. A Volume Reduction Rate (VRR) of 95.0% [86.7-98.0] was achieved. For successful US-PEIT, relatively small total amount of ethanol was needed, on average corresponding to 20.0% [16.7-28.6] of the initial cyst volume. VRR positively correlated with the initial cyst volume and negatively with the presence of complex cyst. Multiple regression analysis showed the presence of complex cyst as an independent predictor of treatment efficacy. CONCLUSION: US-PEIT of thyroid cysts of all sizes was very successful with using total amounts of ethanol, corresponding to ≈20% of the initial cyst volume.

Hypoglycemia as a Symptom of Neoplastic Disease, with a focus on Insulin-like Growth Factors Producing Tumors.

This article reviews the current knowledge of uncommon causes of hypoglycemia, with a focus on neoplastic disease. However, these situations are rare. They commonly accompany severely ill patients and therefore a proper diagnosis is the basis for relevant treatment. Here we discuss the pathophysiological foundation of hypoglycemia - situations caused by increased insulin production or sensitivity - but we also focus on different cytokines which could cause hypoglycemia, especially IGF-II production in what are called nonislet cell tumors. From the clinical perspective we can divide the patients who are affected into "seemingly ill" or "healthy patients" and lead the diagnostic process accordingly.