BackgroundIt is well-established that nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes mellitus (T2DM). Complement-C1q TNF-related protein 5 (CTRP5) is a novel adipokine involved in the regulation of lipid and glucose metabolism. We aimed to assess plasma levels of CTRP5 in patients with NAFLD (n = 22), T2DM (n = 22) and NAFLD with T2DM (NAFLD + T2DM) (n = 22) in comparison with healthy subjects (n = 21) and also to study the association between CTRP5 levels and NAFLD and diabetes-related parameters.MethodsAll subjects underwent anthropometric assessment, biochemical evaluation and liver stiffness (LS) measurement. Insulin resistance (IR) was determined by the homeostasis model assessment (HOMA). Plasma CTRP5 levels were measured by enzyme-linked immunosorbent assay.ResultsWe found significantly lower plasma levels of CTRP5 in patients with NAFLD + T2DM, NAFLD and T2DM (122.52 ± 1.92, 124.7 ± 1.82 and 118.31 ± 1.99 ng/ml, respectively) in comparison with controls (164.96 ± 2.95 ng/ml). In the whole study population, there was a significant negative correlations between CTRP5 and body mass index (r = −0.337; p = 0.002), fasting blood glucose (FBG) (r = −0.488; p < 0.001), triglyceride (TG) (r = −0.245; p = 0.031), HOMA-IR (r = −0.492; p < 0.001), insulin(r = −0.338; p = 0.002), LS (r = −0.544; p < 0.001), alanine aminotransferase (ALT) (r = −0.251; p = 0.027), waist-to-hip ratio (WHR) (r = −0.352; p = 0.002) and waist circumference (WC) (r = −0.357; p = 0.001). After adjustment for BMI, decrease in circulating levels of CTRP5 remained as a significant risk factor for NAFLD, T2DM and NAFLD + T2DM. The receiver operating characteristic (ROC) curves of circulating CTRP5 in predicting NAFLD and T2DM demonstrated an area under the curve (AUC) of 0.763 in T2DM, and 0.659 in NAFLD + T2DM.ConclusionsIt appears that the decreased levels of CTRP5 contribute to the increased risk of T2DM and NAFLD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-015-0099-z) contains supplementary material, which is available to authorized users.

This study shows that after a six-year follow-up in an iodine sufficient area, 6.7% of euthyroid subjects were found to progress to thyroid dysfunction, in particular subclinical hypothyroidism.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin, while both genetic and environmental factors have been demonstrated to be etiologically involved. Recent genome-wide association and replication studies have suggested that anthrax toxin receptor 2 (ANTXR2), interleukin-1 receptor 2 (IL1R2), caspase recruitment domain-containing protein 9 (CARD9), and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) seem to be associated with AS pathogenesis. This case-control study was performed on 349 unrelated AS patients and 469 age- and gender-matched healthy controls, to investigate whether these non-MHC genes (IL1R2 rs2310173, ANTXR2 rs4333130, CARD9 rs4077515, and SNAPC4 rs3812571) influence the AS risk in Iranian population. ANTXR2 rs4333130 allele C (p = 0.0328; OR 0.744, 95% CI 0.598-0.927) and genotype CC (p = 0.0108; OR 0.273, 95% CI 0.123-0.605) were found to be significantly protective against AS. No other associations were found between AS and studied genes. The association between ANTXR2 rs4333130 and AS was independent of HLA-B27 status. Moreover, we found clinical disease severity scores (BASDAI and BASFI) and pain score were higher in ANTXR2 rs4333130 CT genotype. However, we observed that CARD9 allele C (p = 0.012) and genotype CC (p = 0.012) were significant protective factors against AS only in HLA-B27-negative patients, and IL1R2 rs2310173 genotype GT was mildly protective against AS only in HLA-B27-negative status. These findings support the role of non-MHC pathogenic pathways in susceptibility to AS and warrants more comprehensive studies focusing on these non-MHC pathways for developing novel therapeutic strategies.

Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common liver diseases. It is robustly linked to obesity and insulin resistance and is regarded as hepatic manifestation of metabolic syndrome (MetS). Adipokines are involved in the pathophysiology of liver diseases. The aim of this study was to evaluate the plasma concentrations of CTRP1 (complement-C1q TNF-related protein 1) in 22 patients with NAFLD, 22 patients with type 2 diabetes mellitus (T2DM), 22 patients with NAFLD+T2DM and 21 healthy controls, as well as their correlation with the level of metabolic and hepatic parameters. Plasma concentration of CTRP1 was measured with ELISA method. Plasma concentration of CTRP1 in patients with NAFLD, T2DM and NAFLD+T2DM were significantly higher than healthy subjects (p<0.0001). Moreover, we observed significant positive correlations between plasma level of CTRP1 and fasting blood glucose (FBG) (p<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (p<0.001), body mass index (BMI) (p = 0.001), alanine amino transferase (ALT) (p = 0.002), gamma glutamyl transferase (γ-GT) (p<0.001) and liver stiffness (LS) (p<0.001). Our results indicate the strong association of CTRP1 with insulin resistance in NAFLD. Also, it seems that CTRP1 can be considered as an emerging biomarker for NAFLD, however, more studies are necessary to unravel the role of CTRP1 in NAFLD pathogenesis.

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ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by persistent synovitis, ultimately leading to cartilage and bone degeneration. Natural Killer cells and CD28 null T-cells are suspected as role players in RA pathogenesis. These cells are similar in feature and function, as they both exert their cytotoxic effect via Killer Cell Immunoglobulin- Like Receptors (KIR) on their surface. KIR genes have either an inhibitory or activating effect depending on their intracytoplasmic structure. Herein we genotyped 16 KIR genes, 3 pseudo genes and 6 HLA class І genes as their corresponding ligands in RA patients and control subjects.MethodsIn this case-control study, KIR and HLA genes were genotyped in 400 RA patients and 372 matched healthy controls using sequence-specific primers (SSP-PCR). Differences in the frequency of genes and haplotypes were determined by χ² test.Results KIR2DL2, 2DL5a, 2DL5b and activating KIR: KIR2DS5 and 3DS1 were all protective against RA. KIR2DL5 removal from a full Inhibitory KIR haplotype converted the mild protection (OR = 0.56) to a powerful predisposition to RA (OR = 16.47). Inhibitory haplotype No. 7 comprising KIR2DL5 in the absence of KIR2DL1 and KIR2DL3 confers a 14-fold protective effect against RA.ConclusionIndividuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.

Increased fructose consumption is linked to insulin resistance, weight gain, hyperlipidemia and hypertension. Although the advantages of several dietary restriction regimens have been demonstrated, the effects of alternate-day fasting (ADF) on fructose-induced insulin resistance have not yet been studied. This study is based on a new modification on ADF by combining the fructose-rich solution (10% w/v) and regular mice diet. Mice were randomly allocated into four groups: ADF50% (50% restriction in chow food intake but ad libitum fructose drink), ADF100% (100% restriction for chow food but ad libitum fructose drink), control (ad libitum chow food intake plus tap water) and daily food and fructose (DFF) (had free access to both chow and fructose solution). Biweekly fasting blood sugar (FBS), glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted. All groups gained weight during the study (p < 0.05). Body weights of DFF and control groups did not differ from that of ADF groups, but ADF50% gained more (p < 0.01) weights than ADF100% through the study. Total calorie intake (feed + fast days) of ADF50% was higher than that of ADF100% (p < 0.001) and control (p < 0.03). In addition, ADF groups consumed more energy than the control and DFF groups in feed (ad libitum) days (p < 0.05). At the end of the study, the mean FBS levels in the control and ADF100% groups were similar and significantly lower in relation to that of DFF and ADF50% groups (p < 0.01). Measurements of area under the curve in GTT and ITT revealed that the ADF100% group was more insulin-sensitive than the DFF and ADF50% groups. In conclusion, these data suggest that the ADF100% improves fructose-induced insulin resistance in mice.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling which is overexpressed in the liver of diabetic animals. The aims of this study were to generate liver-specific PTP1B knockout mice using a PTP1B‑short hairpin RNA (shRNA) plasmid and to investigate the effect of PTP1B inhibition on plasma glucose levels in streptozotocin-induced diabetic mice. We first validated the hydrodynamic tail vein injection in mice using a vector carrying the luciferase gene. Expression of the PTP1B gene was quantified by real-time PCR. The level of phosphorylated Akt was examined by western blot analysis. The injection of the plasmid containing firefly luciferase revealed that the highest transfer of the vector into the liver was obtained 24 h after the injection of 20 µg plasmid. The injection of PTP1B-shRNA, but not the scrambled shRNA plasmid, resulted in a reduction in PTP1B expression levels by up to 84% in the liver of the diabetic mice. Plasma glucose levels following the injection of PTP1B-shRNA remained significantly lower in the diabetic mice for 5 days. In addition, mice receiving PTP1B-shRNA in the basal and insulin-stimulated states had higher levels of Akt phosphorylation in the liver cells compared with mice that were injected with the scrambled sequence (35 and 60%, respectively; p<0.01). Furthermore, PTP1B overexpression was observed in the muscle, liver, adipose, heart and kidney tissues of the diabetic mice. The data from this study demonstrate that PTP1B inhibition may be a promising approach for lowering plasma glucose levels in diabetic patients. However, further studies using non-viral carriers are required to deliver the plasmid safely into the liver.