Predictors of Impaired Glucose Regulation in Patients with Non-Alcoholic Fatty Liver Disease

Introduction. Many patients with non-alcoholic fatty liver disease (NAFLD) have impaired glucose regulation or type 2 diabetes mellitus (DM). We investigated characteristics of NAFLD patients associated with hyperglycemia. Methods. During a 2-hour oral glucose tolerance test (OGTT), serum glucose and insulin were measured in 152 NAFLD patients. Results. 48.7% of NAFLD patients had hyperglycemia. Age (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.03–1.13), body mass index (BMI) (OR = 1.12, 95% CI: 1.01–1.25), and lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.95, 95% CI: 0.92–0.98) proved to be independent predictors of hyperglycemia. After OGTT, 30 min insulin was lower in hyperglycemic patients (74.2 ± 49.7 versus 94.5 ± 53.9 μIU/mL, P = 0.02), while 90 min insulin (170.1 ± 84.6 versus 122.9 ± 97.7 μU/mL, P = 0.01) and 120 min insulin (164.0 ± 101.2 versus 85.3 ± 61.9 μIU/mL, P < 0.01) were higher. Conclusions. NAFLD patients with higher BMI, lower HDL-C, or older age were more likely to have impaired glucose metabolism. An OGTT could be of value for early diagnosis of DM among this population

Immunological parameters of latent autoimmune diabetes of adults (LADA)

Latent Autoimmune Diabetes of adults (LADA) is characterized by humoral and cellular immune responses that result in destruction of the pancreatic b-cells and the development of clinical diabetes. In this study the followings were investigated a) clinical and anthropometric characteristics (GAD65 Abs, C-peptide, BMI, type of treatment), b) cytokine production (IFN-γ, IL-12 και IL-10) and c) gene polymorphism ((TNF-α-308A/G, TGF-β1- codon 10 T/C, TGF-β1- codon 25 G/C, IL-10-1082G/A, IL-10-819T/C, IL-10-592A/C, IL-6- 174G/C, IFN-Y-874A/T) in diabetics type 2, type LADA and healthy controls. Radioimmunoassays, enzyme-linked immunosorbent assays, from cytometry, polymerase chain reaction, genotypic analysis were the methods used. Our purposes were the determination of factors that cause inflammation and the investigation of new immunological or genotypic markers that correlate with the development of this disease. Our findings succeeded to define, probably for the first time, tensions and associations of certain immuno-genotypic and immunophenotypic parameters with the development of Diabetes type 2 and Diabetes LADA, and additionally a possible pathogenic role of specific glycoproteins with certain immunologic and proinflammatory properties with the promotion and development of these diseases.Ο Διαβήτης τύπου LADA χαρακτηρίζεται από χρόνιες χημικές και κυτταρικές αντιδράσεις που καταλήγουν στην καταστροφή των β κυττάρων του παγκρέατος και την εκδήλωση κλινικού διαβήτη. Στην ερευνητική αυτή εργασία μελετήθηκαν α) κλινικο-εργαστηριακά χαρακτηριστικά (GAD65 Abs, C-πεπτίδιο, BMI, είδος αγωγής) β) παραγωγή κυτταροκινών IFN-γ, IL-12 και IL-10 και γ) πολυμορφισμός γονιδίων (TNF-α-308A/G, TGF-β1- κωδικόνιο 10 T/C, TGF-β1- κωδικόνιο 25 G/C, IL-10-1082G/A, IL-10-819T/C, IL-10-592A/C, IL-6- 174G/C, IFN-Y-874A/T) σε διαβητικούς τύπου 2, τύπου LADA και φυσιολογικούς μάρτυρες. Οι μεθοδολογίες που χρησιμοποιήθηκαν ήταν: ανοσοενζυμικές, ραδιοανοσολογικές, κυτταροκαλλιέργειες, κυτταρομετρία ροής, αλυσιδωτή αντίδραση πολυμερισμού DNA, γενοτυπική ανάλυση αλληλομόρφων των γονιδίων των κυτταροκινών. Κύριοι στόχοι μας ήταν ο προσδιορισμός παραγόντων που προκαλούν τη φλεγμονή ή η ανεύρεση νέων ανολογικών η γενοτυπικών δεικτών που συνδέονται με την εκδήλωση της νόσου. Τα αποτελέσματα της εργασίας αυτής αναδεικνύουν για πρώτη ίσως φορά τάσεις και συσχετίσεις ανοσογενοτυπικών και ανοσοφαινοτυπικών παραμέτρων με την εκδήλωση του Διαβήτη τύπου LADA και Διαβήτη τύπου 2, καθώς επίσης και έναν παθογενετικό ρόλο συγκεκριμένων γλυκοπρωτεϊνών στην πρόκληση των κλινικών αυτών οντοτήτων

Predictors of Impaired Glucose Regulation in Patients with Non-Alcoholic Fatty Liver Disease

Introduction. Many patients with non-alcoholic fatty liver disease (NAFLD) have impaired glucose regulation or type 2 diabetes mellitus (DM). We investigated characteristics of NAFLD patients associated with hyperglycemia. Methods. During a 2-hour oral glucose tolerance test (OGTT), serum glucose and insulin were measured in 152 NAFLD patients. Results. 48.7% of NAFLD patients had hyperglycemia. Age (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.03-1.13), body mass index (BMI) (OR = 1.12, 95% CI: 1.01-1.25), and lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.95, 95% CI: 0.92-0.98) proved to be independent predictors of hyperglycemia. After OGTT, 30 min insulin was lower in hyperglycemic patients (74.2 +/- 49.7 versus 94.5 +/- 53.9 mu IU/mL, P = 0.02), while 90 min insulin (170.1 +/- 84.6 versus 122.9 +/- 97.7 mu U/mL, P = 0.01) and 120 min insulin (164.0 +/- 101.2 versus 85.3 +/- 61.9 mu IU/mL, P &lt; 0.01) were higher. Conclusions. NAFLD patients with higher BMI, lower HDL-C, or older age were more likely to have impaired glucose metabolism. An OGTT could be of value for early diagnosis of DM among this population

Serum Chemerin Concentrations Associate with Beta-Cell Function, but Not with Insulin Resistance in Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)

The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P&lt;0.004), but not with circulating glucose, insulin, lipids or liver enzymes (all P&gt;0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P&gt;0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI_cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI_ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD

Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes

We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = &lt;35 years old or middle-aged (36&ndash;64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications

Associations between Serum Chemerin Levels and Anthropometric and Metabolic Variables.

<p>Data are given as partial Spearman correlation coefficients r_s and respective <i>P</i> values.</p><p>*Adjusted for sex or sex and BMI only.</p><p>**Adjusted for age or age and BMI only.</p><p>Significant correlations (<i>P</i><0.05) are highlighted using bold print.</p><p>Associations between Serum Chemerin Levels and Anthropometric and Metabolic Variables.</p

Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes

We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = &lt;35 years old or middle-aged (36-64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications

Basic Characteristics of Study Participants.

<p>Data are missing for 16–22% of the total study population for the lipid parameters, for 10–11% for the liver enzymes and for 6% for C-peptides and derived indices.</p><p>*<i>P</i><0.05,</p><p>**<i>P</i><0.01,</p><p>***<i>P</i><0.001 compared to controls.</p><p>Basic Characteristics of Study Participants.</p

Effects of olanzapine on cytokine profile and brain-derived neurotrophic factor in drug-naive subjects with first-episode psychosis

Immunological abnormalities have been implicated in schizophrenia. On the other hand, antipsychotics may exert immunomodulatory effects, by triggering pro-inflammatory and anti-inflammatory agents through complex homeostatic mechanisms, which seem to be implicated in medication responsiveness and in the presence or not of adverse effects. There is evidence that olanzapine, a second generation antipsychotic, may increase synapse formation and neurogenesis through alterations in the levels of cytokines and neurotrophic factors. In the present study, we recruited 14 drug-naive inpatients with first-episode schizophrenia (male:female ratio, 7:7) with a mean age of 26.5 years. The positive and negative syndrome scale (PANSS) scores and serum levels of a broad spectrum of cytokines and of brain-derived neurotrophic factor (BDNF) were recorded twice, once at baseline prior to the initiation of olanzapine treatment and 8 weeks later, once the dose of olanzapine had stabilized. Subsequently, the associations between the PANSS scores and the measured markers were examined. Correlation analyses revealed that follow-up PANSS(negative) positively correlated with baseline interleukin (IL)-6 (=0.685, P=0.007) and baseline IL-27 levels (=0.785, P=0.001). Furthermore, the percentage change in PANSS(negative) [(PANSS-(follow-up) - PANSS-(baseline))/PANSS-baseline; PANSS(negative%))] positively correlated with baseline IL-27 (=0.785, P=0.001) and baseline IL-6 levels (=0.685, P=0.007). Finally, linear regression revealed that follow-up PANSS(negative) was associated with baseline IL-27 (R-2=0.301, P=0.042), PANSS(negative%) was associated with baseline IL-6 (R-2=0.301, P=0.042) and baseline IL-27 levels (R-2=0.446, P=0.009). Thus, these findings indicate that IL-27 and IL-6 may be trait markers in patients being administered olanzapine monotherapy at the onset of schizophrenia. However, further studies are warranted in order to replicate these associations and to confirm their potential use as biomarkers of treatment effectiveness and safety, as well as to explore novel immunomodulatory strategies for the treatment of schizophrenia