Katarzyna Bergmann

Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers

Abstract Increasing incidence of type 2 diabetes is a major health problem of the modern world and requires new diagnostic tools to assess early metabolic disorders, particularly insulin resistance. The link between obesity, inflammation and insulin resistance indicates the important secretory role of adipose tissue. Proinflammatory factors (cytokines, adipokines) produced by enlarged adipose tissue are related to impaired glucose metabolism. Adipokines act as paracrine factors in adipose tissue and as endocrine hormones in the liver, muscles and central nervous system. Novel adipokines secreted from adipocytes such as retinol binding protein-4 (RBP-4), vaspin, omentin, chemerin, fibroblast growth factor 21 (FGF21), adipocyte fatty acid-binding protein (A-FABP) and dipeptidyl peptidase 4 (DPP4) demonstrate pleiotropic activity and their insulin-sensitizing or enhancing insulin resistance properties have not been clearly confirmed yet. In spite of the lack of standardized automated assay methods currently available for these novel biomarkers, promising results from several studies emphasize that they might potentially be useful prognostic factors for diabetes and its complications, especially in individuals without the typical symptoms of metabolic syndrome.

Metabolic Syndrome and Menopause: Pathophysiology, Clinical and Diagnostic Significance.

Menopause is a risk factor for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular diseases. MetS is a constellation of interdependent factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension. The prevalence of MetS in postmenopause is due to loss of the protective role of estrogens and increased circulating androgens resulting in changes to body fat distribution and development of abdominal obesity. Excessive visceral adipose tissue plays an important role due to synthesis and secretion of bioactive substances such as adipocytokines, proinflammatory cytokines, reactive oxygen species, prothrombotic, and vasoconstrictor factors. MetS may also impact risk assessment of breast cancer, osteoporosis and chronic kidney disease, and quality of life during the menopausal transition. Increased MetS has stimulated the exploration of new laboratory tests for early detection and therapies.

Metabolic Syndrome and Menopause

Menopause is a risk factor for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular diseases. MetS is a constellation of interdependent factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension. The prevalence of MetS in postmenopause is due to loss of the protective role of estrogens and increased circulating androgens resulting in changes to body fat distribution and development of abdominal obesity. Excessive visceral adipose tissue plays an important role due to synthesis and secretion of bioactive substances such as adipocytokines, proinflammatory cytokines, reactive oxygen species, prothrombotic, and vasoconstrictor factors. MetS may also impact risk assessment of breast cancer, osteoporosis and chronic kidney disease, and quality of life during the menopausal transition. Increased MetS has stimulated the exploration of new laboratory tests for early detection and therapies.

How Do Apolipoproteins ApoB and ApoA-I Perform in Patients with Acute Coronary Syndromes

How Do Apolipoproteins ApoB and ApoA-I Perform in Patients with Acute Coronary Syndromes Acute coronary syndromes are the leading cause of hospitalization and death. Results from recent studies suggest that apolipoprotein measurement and apoB:apoA-I are superior to traditional lipids in the estimation of coronary risk. We compared apolipoprotein concentrations and apoB:apoA-I with traditional lipid measures and atherogenic indices in patients diagnosed with acute coronary syndromes (ACS) within 6 hrs from the onset of chest pain. A study group consisted of 227 patients diagnosed with ACS (STEMI=60, NSTEMI=66 and UA=105). Clinically healthy volunteers (n=85) served as controls. Measurements of cardiac TnI, lipid profile, hsCRP, apolipoprotein A-I and apoB100 were performed and apoB:apoA-I, TC-HDL-C, LDL-C:HDL-C ratios were calculated. Patients had increased LDL-C (>3.0 mmol/L) and non-HDL-C (>3.4 mmol/L). Triglycerides were below the cut-off value, but patients had significantly higher TG concentrations and lower HDL-C compared to controls (p<0.001). Apo B and apoA-I concentration in patients remained within the accepted range. Atherogenic indices TC:HDL-C, LDL-C:HDL-C and apoB:apoA-I were significantly increased in patients. ApoB:apoA-I ratio in ACS males was within low risk whereas in females corresponded to medium risk. ApoB:apoA-I and LDL-C:HDL-C ratios were of good diagnostic utility for discrimination between patients and controls (AUC 0.71 and 0.79; respectively). ApoB:apoA-I and LDL-C:HDL-C were of very good diagnostic utility for discrimination between STEMI patients and controls (AUC 0.80 and 0.84). We could not show the superiority of apoB:apoA-I over LDL-C:HDL-C as the discrimination power of both was almost identical. Determination of apolipoproteins should not be recommended for routine clinical use, however, incorporating apoB and apoB:apoA-I into risk assessment could provide additional important information on cardiovascular risk. Koliko Su Efikasni Apolipoproteini ApoB I ApoA-I Kod Pacijenata Sa Akutnim Koronarnim Sindromima Akutni koronarni sindrom predstavlja vodeći uzrok hospitalizacija i smrti. Rezultati skorašnjih studija pokazuju da se u proceni koronarnog rizika bolje pokazalo merenje apolipoproteina i apoB:apoA-I nego tradicionalnih lipida. Uporedili smo koncentracije apolipoproteina i apoB:apoA-I sa tradicionalnim lipidskim merama i aterogenim indeksima kod pacijenata sa dijagnozom akutnog koronarnog sindroma (ACS) u roku od 6 sati od nastanka bola u grudima. Proučavanu grupu činilo je 227 pacijenata sa dijagnozom ACS (STEMI=60, NSTEMI=66 i nestabilna angina pektoris=105). Klinički zdravi dobrovoljci (n=85) služili su kao kontrola. Izmereni su srčani TnI, lipidski profil, hsCRP, apolipoprotein A-I i apoB100 i izračunati odnosi apoB:apoA-I, TC-HDL-C, LDL-C:HDL-C. Pacijenti su imali povišen LDL-C (>3,0 mmol/L) i ne-HDL-C (>3,4 mmol/L). Trigliceridi su bili ispod cut-off vrednosti, ali pacijenti su imali značajno više koncentracije TG i niži HDL-C u poređenju sa kontrolama (p<0,001). Koncentracija apo B i apoA-I kod pacijenata ostala je u okviru prihvaćenog opsega. Aterogeni indeksi TC:HDL-C, LDL-C:HDL-C i apoB:apoA-I bili su značajno viši kod pacijenata. Odnos apoB:apoA-I kod muškaraca sa ACS ukazivao je na nizak rizik, dok je kod žena odgovarao srednjem riziku. Odnosi apoB:apoA-I i LDL-C:HDL-C bili su dijagnostički korisni za razlikovanje pacijenata od kontrola (AUC 0,71 i 0,79). ApoB:apoA-I i LDL-C:HDL-C bili su veoma dijagnostički korisni za diskriminaciju između pacijenata sa STEMI i kontrola (AUC 0,80 i 0,84). Nismo uspeli da pokažemo superiornost apoB-apoA-I u odnosu na LDL-C:HDL-C pošto je njihova diskriminatorna moć gotovo identična. Određivanje apolipoproteina ne bi trebalo preporučivati za rutinsku kliničku upotrebu, međutim, uključivanje apoB i apoB:apoA-I u procenu rizika moglo bi obezbediti dodatne važne informacije o kardiovaskularnom riziku.

Is there an association of allergy and cardiovascular disease

Cardiovascular diseases and allergic diseases occur commonly in developed countries. They lead to serious health complications and significantly impair the quality of life. Both types of diseases are characterized by excessive inflammatory processes. Recent studies suggest a link between allergy and an increased risk of cardiovascular disease, resulting from overactivity of the immune system in allergic diseases and increased synthesis of proinflammatory mediators, which has been well documented in the pathogenesis of atherosclerosis. The aim of this article is to present current data on the role of proinflammatory factors in the pathogenesis of cardiovascular diseases and allergies and on potential relationship between these disorders.

Secreted frizzled-related protein 4 (SFRP4) and fractalkine (CX3CL1) - Potential new biomarkers for β-cell dysfunction and diabetes.

The discovery of new risk factors for diabetes is a major challenge for contemporary science. Pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to adipose tissue dysfunction. The aim of this review was to describe recently discovered cytokines: fractalkine (CX3CL1, FKN) and secreted frizzled-related protein 4 (SFRP4) as potential biomarkers of early β cell dysfunction and diabetes. The association of CX3CL1 and SFRP4 with low-grade inflammation in adipose tissue links obesity with disturbances in insulin secretion and impaired glucose metabolism, therefore it indicates new therapeutic and preventive targets in both healthy and diabetic subjects.

25-Hydroxyvitamin D, biomarkers of eosinophilic inflammation, and airway remodeling in children with newly diagnosed untreated asthma.

BACKGROUND Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be related to airway remodeling and eosinophilia. Periostin is proposed as a key molecule that links remodeling and eosinophilic inflammation. OBJECTIVE We evaluated the association of 25(OH)D concentration with periostin, peripheral blood eosinophil counts, and immunoglobulin E (IgE) in children with newly diagnosed asthma. METHODS The study included 150 children: 110 with atopic asthma and 40 constituted a reference group. Fasting blood was collected for cell counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive protein (CRP) concentrations. RESULTS Significantly lower 25(OH)D, elevated IgE concentrations, and eosinophil counts were found in children with asthma compared with the reference group (p = 0.0001). A lower forced expiratory volume in the first second of expiration percentage predicted value was associated with a lower 25(OH)D value in children with asthma. The bronchodilator reversibility was inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The children with asthma and with a 25(OH)D deficient concentration (≤20 ng/mL) had higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with a sufficient 25(OH)D concentration (≥30 ng/L). Additional analysis revealed statistically significant differences (p = 0.013) when comparing periostin concentrations between subjects with a 25(OH)D deficient concentration (≤20 ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on eosinophilia, whereas IgE concentrations were associated with increased eosinophils, and the effect of periostin on eosinophilia was small although significant. Multivariate regression, including 25(OH)D concentration, CRP level, eosinophil counts, and sex, accounted for 7% of periostin variation in subjects with asthma. CONCLUSION In newly diagnosed pediatric asthma, 25(OH)D concentrations revealed a small although significant association with periostin levels but no effect on eosinophilia. A low vitamin D concentration may increase airway remodeling induced by inflammatory mediators, but further clinical studies aimed to explain the causal link between vitamin D insufficiency and asthma are needed.BACKGROUND Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be related to airway remodeling and eosinophilia. Periostin is proposed as a key molecule that links remodeling and eosinophilic inflammation. OBJECTIVE We evaluated the association of 25(OH)D concentration with periostin, peripheral blood eosinophil counts, and immunoglobulin E (IgE) in children with newly diagnosed asthma. METHODS The study included 150 children: 110 with atopic asthma and 40 constituted a reference group. Fasting blood was collected for cell counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive protein (CRP) concentrations. RESULTS Significantly lower 25(OH)D, elevated IgE concentrations, and eosinophil counts were found in children with asthma compared with the reference group (p = 0.0001). A lower forced expiratory volume in the first second of expiration percentage predicted value was associated with a lower 25(OH)D value in children with asthma. The bronchodilator reversibility was inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The children with asthma and with a 25(OH)D deficient concentration (≤20 ng/mL) had higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with a sufficient 25(OH)D concentration (≥30 ng/L). Additional analysis revealed statistically significant differences (p = 0.013) when comparing periostin concentrations between subjects with a 25(OH)D deficient concentration (≤20 ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on eosinophilia, whereas IgE concentrations were associated with increased eosinophils, and the effect of periostin on eosinophilia was small although significant. Multivariate regression, including 25(OH)D concentration, CRP level, eosinophil counts, and sex, accounted for 7% of periostin variation in subjects with asthma. CONCLUSION In newly diagnosed pediatric asthma, 25(OH)D concentrations revealed a small although significant association with periostin levels but no effect on eosinophilia. A low vitamin D concentration may increase airway remodeling induced by inflammatory mediators, but further clinical studies aimed to explain the causal link between vitamin D insufficiency and asthma are needed.

The influence of sample freezing at -80°C for 2-12 weeks on glycated haemoglobin (HbA1c) concentration assayed by HPLC method on Bio-Rad D-10© auto-analyzer.

Introduction The aim of the study was to evaluate the effect of a single freeze/thaw cycle on HbA1c concentrations measured by commercially available HPLC method. Materials and methods Study included 128 whole blood samples collected from diabetic patients (N = 60) and healthy volunteers (N = 68). HbA1c concentrations were measured in fresh blood samples. Then samples were frozen at - 80 °C for up to 12 weeks. HbA1c was assayed by ion-exchange HPLC method on Bio-Rad D-10® analyzer. Variables were compared using Wilcoxon and ANOVA Kruskal-Wallis tests. Bias between HbA1c measured in fresh and frozen samples was calculated. The comparability of HbA1c concentrations was assessed by Bland-Altman plot. Results Median (IQR) HbA1c concentration was 45.3 (36.6–61.2) mmol/mol for fresh and 45.3 (36.6–60.6) mmol/mol for frozen/thawed samples. No significant difference in HbA1c concentrations was found comparing fresh and frozen/thawed samples (P = 0.070) in the whole group, as well as in healthy and diabetic subjects. The median calculated bias between fresh and frozen/thawed samples was 0% in whole group and healthy subjects, and 1.19% in diabetic patients. No significant difference was found between the biases according to baseline HbA1c values (P = 0.150). The Bland-Altman plot analysis showed a positive bias of 0.4% (95% CI: - 2.8 - 3.7%), which indicates high compliance between HbA1c values and no relevant influence of sample freezing on clinical significance of HbA1c measurement. Conclusions Storage for up to 12 weeks at – 80 °C with a single freeze/thaw cycle does not affect HbA1c concentrations measured with HPLC method on Bio-Rad D-10® analyzer.

Gender differences in association of serum nesfatin-1 with selected metabolic risk factors in normoglycemic subjects: A preliminary study.

In recent years, many new proteins and hormones involved in the regulation of adipose tissue metabolism and activity of the hunger/satiety center in the central nervous system have been discovered. Nesfatin-1, first described by Oh-I et al. in 2006, is an 82-amino acid polypeptide encoded in the N-terminal region of Nucleobindin 2 (NUCB2) that exhibits an anorexigenic effect. Although nesfatin-1/NUCB2 production was initially considered to occur mainly in hypothalamic nuclei, studies have revealed highest expression in endocrine cells of the gastric mucosa, as well as in other peripheral tissues, like pancreatic islets, adipose tissue, and reproductive organs. Several animals studies have described insulinotropic effect of nesfatin-1/NUCB2 and its ability to decrease blood glucose levels via activation of L-type calcium channels in pancreatic β-cells or altering AKT phosphorylation and glucose transporter GLUT4 translocation into the cell membrane in muscles, adipocytes, and the liver. However, these findings have not been confirmed in humans. In the present study we investigated whether serum nesfatin-1/NUCB2 may be a novel candidate biomarker of impaired glucose metabolism in subjects without diabetes. The study was performed on 80 normoglycemic, nonobese (body mass index [BMI] 17.5–28 kg/m), nonsmoking subjects aged 25–40 years (32 women, 48 men). Fasting plasma glucose, HbA1c, serum lipid profile, insulin, C-reactive protein, and apolipoproteins AI and B were measured using autoanalyzers (Architect ci8200; Abbott Laboratories, Abbott Park, IL, USA; Cobas e411; Roche Diagnostics, Indianapolis, IN, USA). Adiponectin (human adiponectin; BioVendor R&D, Brno, Czech Republic) and nesfatin-1/NUCB2 (Nesfatin-1 (1–82) human; Phoenix Pharmaceuticals, Burlingame, CA, USA) concentrations were determined by ELISA. Nesfatin-1/NUCB2 concentrations were significantly higher in women than men (1.28 vs 0.82 ng/mL; P = 0.02). Different associations between nesfatin-1/ NUCB2 and glucose insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HbA1c were found in women and men (Table 1), which may indicate that its activity depends on gender and BMI. In women,

Gender differences in association of serum nesfatin-1 with selected metabolic risk factors in normoglycemic subjects: A preliminary study在血糖正常的受试者中血清nesfatin-1与选定的代谢危险因素之间关系的性别差异：一项初步研究

In recent years, many new proteins and hormones involved in the regulation of adipose tissue metabolism and activity of the hunger/satiety center in the central nervous system have been discovered. Nesfatin-1, first described by Oh-I et al. in 2006, is an 82-amino acid polypeptide encoded in the N-terminal region of Nucleobindin 2 (NUCB2) that exhibits an anorexigenic effect. Although nesfatin-1/NUCB2 production was initially considered to occur mainly in hypothalamic nuclei, studies have revealed highest expression in endocrine cells of the gastric mucosa, as well as in other peripheral tissues, like pancreatic islets, adipose tissue, and reproductive organs. Several animals studies have described insulinotropic effect of nesfatin-1/NUCB2 and its ability to decrease blood glucose levels via activation of L-type calcium channels in pancreatic β-cells or altering AKT phosphorylation and glucose transporter GLUT4 translocation into the cell membrane in muscles, adipocytes, and the liver. However, these findings have not been confirmed in humans. In the present study we investigated whether serum nesfatin-1/NUCB2 may be a novel candidate biomarker of impaired glucose metabolism in subjects without diabetes. The study was performed on 80 normoglycemic, nonobese (body mass index [BMI] 17.5–28 kg/m), nonsmoking subjects aged 25–40 years (32 women, 48 men). Fasting plasma glucose, HbA1c, serum lipid profile, insulin, C-reactive protein, and apolipoproteins AI and B were measured using autoanalyzers (Architect ci8200; Abbott Laboratories, Abbott Park, IL, USA; Cobas e411; Roche Diagnostics, Indianapolis, IN, USA). Adiponectin (human adiponectin; BioVendor R&D, Brno, Czech Republic) and nesfatin-1/NUCB2 (Nesfatin-1 (1–82) human; Phoenix Pharmaceuticals, Burlingame, CA, USA) concentrations were determined by ELISA. Nesfatin-1/NUCB2 concentrations were significantly higher in women than men (1.28 vs 0.82 ng/mL; P = 0.02). Different associations between nesfatin-1/ NUCB2 and glucose insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HbA1c were found in women and men (Table 1), which may indicate that its activity depends on gender and BMI. In women,