Immigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) associated with obesity. We investigated the relationship between diabetes and adipose tissue distribution in a group of younger T2DM subjects from Norway and Pakistan. Eighteen immigrant Pakistani and 21 Norwegian T2DM subjects (age 29-45, 49% men) were included. They underwent anthropometrical measurements including bioelectrical impedance analysis, CT scans measuring fatty infiltration in liver and adipose and muscle tissue compartments in mid-abdomen and thigh, a euglycemic clamp, and blood samples for serum insulin and plasma glucose, adipokines and inflammation markers. Adipose tissue distribution was similar in Norwegians and Pakistanis. Pakistanis, but not Norwegians, showed a negative correlation between insulin sensitivity and visceral adipose tissue (VAT, rs = - 0.704, p = 0.003). Subcutaneous adipose tissue (SAT) correlated to leptin in both Pakistanis and Norwegians (rs = 0.88, p
In the nonpregnant population, there is extensive evidence of a systemic low-grade inflammatory status in relation to excess adipose tissue. Less is known about the relation during pregnancy.
Our main objective was therefore to explore the effect of pregnancy on adiposity-related systemic inflammation.
This study is a longitudinal cohort study of 240 pregnant women of Scandinavian heritage at Oslo University hospital-Rikshospitalet, Norway from 2002 to 2005. The inflammatory markers (C-reactive protein [CRP], Interleukin-6 [IL-6], monocyte chemoattractant protein 1 [MCP-1], IL1-Ra, tumor necrosis factor receptor II, and IL-10) were measured at four timepoints during pregnancy and analyzed by enzyme immuno-assay. The women were categorized based on BMI at inclusion (BMI 30 kg/m(2)). Data were analyzed by Friedman-test, Wilcoxon signed rank test, or Kruskal-Wallis test as appropriate.
Maternal adiposity was associated with significantly higher circulatory levels of several inflammatory markers (CRP, MCP-1, IL-6, and IL-1Ra). However, this proinflammatory upregulation was not evident toward the end of pregnancy, as levels of CRP, MCP-1, and IL-6 were not any longer significantly different between the BMI categories.
Although normal pregnancy exhibits proinflammatory features, this does not seem to have additive or synergistic effects on the inflammation associated with adiposity. On the contrary, we found that the BMI-dependent increase in proinflammatory markers was not evident at the end of pregnancy.
Research Institute of Internal Medicine, The National Hospital, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway; K.G. Jebsen - Thrombosis Research and Expertise Center (TREC), University of Tromsø, Tromsø, Norway. Electronic address: firstname.lastname@example.org.
Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during inflammation and involved in transmigration of leukocytes and T-cell activation. We hypothesized that ALCAM might be associated with recurrent events in patients with acute coronary syndromes (ACS).
ALCAM was measured in serum obtained on admission, at discharge, 1 month and 6 months in a subgroup of 5165 patients admitted with ACS and included in the PLATelet inhibition and patient Outcomes (PLATO) trial (NCT00391872). The association between ALCAM and the composite endpoint and its components, including cardiovascular (CV) death, non-procedural spontaneous myocardial infarction (MI) or stroke during 1-year follow-up, was assessed by Cox proportional hazards models with incremental addition of clinical risk factors and biomarkers (including high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15).
The median (Q1-Q3) concentration of ALCAM at admission was 97 (80-116) ng/mL. A 50% higher level of ALCAM on admission was associated with a hazard ratio (HR) of 1.16 (95% confidence interval [1.00-1.34] p = 0.043) for the composite endpoint in fully adjusted analysis, mainly driven by the association with CV death (HR 1.45 [1.16-1.82] p = 0.0012).
In patients with ACS, admission level of ALCAM was independently associated with adverse outcome including CV death even after adjustment for established inflammatory and cardiac biomarkers.
Chronic heart failure (HF) is in part characterized by immune activation and inflammation, and factors that regulate lymphocyte trafficking and inflammation may contribute to the progression of this disorder. The homeostatic chemokine CCL21 is a potent regulator of T-cell migration into non-lymphoid tissue and may exert inflammatory properties and influence tissue remodelling. We therefore investigated CCL21 levels and association with fatal outcomes in patients with chronic HF.
Plasma CCL21 was measured at randomization in 1456 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and in 1145 from the GISSI-HF trial. Association between CCL21 levels [given below as hazard ratio (HR) with 95% confidence interval (CI) for 1 SD increase] with all-cause (n = 741) or cardiovascular (CV) mortality (n = 576) was evaluated with multivariable Cox proportional hazard models, adjusting for clinical risk factors, C-reactive protein, and NT-proBNP. In multivariable Cox models, CCL21 was associated with higher risk of all-cause mortality (HR 1.16, 95% CI 1.02-1.32; P = 0.020) and CV mortality (HR 1.20, 95% CI 1.08-1.33; P
It remains uncertain whether activation of the complement system, assessed by the soluble terminal C5b-9 complement complex (plasma TCC), is associated with future risk of incident venous thromboembolism (VTE).
To investigate the association between plasma levels of TCC and future risk of incident VTE in a nested case-control study, and to explore genetic variants associated with TCC using protein quantitative trait loci (pQTL) analysis of exome sequencing data.
We sampled 415 VTE cases and 848 age- and sex-matched controls from a population-based cohort, the Tromsø study. Logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE across quartiles of plasma levels of TCC. Whole exome sequencing was conducted using the Agilent SureSelect 50Mb capture kit.
The risk of VTE increased across increasing quartiles of plasma TCC, particularly for unprovoked VTE. Participants with TCC in the highest quartile (>1.40 CAU/mL) had an OR for unprovoked VTE of 1.74 (95% CI: 1.10-2.78) compared to those with TCC in the lowest quartile (=0.80 CAU/mL) in analyses adjusted for age, sex and body mass index. A substantially higher risk for VTE was observed in samples taken shortly before VTE event. We found no association between genome-wide or complement-related gene variants and plasma levels of TCC.
We found that high levels of plasma TCC were associated with VTE risk, and unprovoked events in particular. There was no genome-wide association between gene variants and plasma levels of TCC. This article is protected by copyright. All rights reserved.
The inflammatory response to community-acquired pneumonia (CAP) is orchestrated through activation of cytokine networks and the complement system. We examined the association of multiple cytokines and the terminal complement complex (TCC) with microbial aetiology, disease severity and short-term outcome.
Plasma levels of 27 cytokines and TCC were analysed in blood samples obtained at hospital admission, clinical stabilization and 6-week follow-up from 247 hospitalized adults with CAP. Fourteen mediators were included in final analyses. Adverse short-term outcome was defined as intensive care unit (ICU) admission and 30-day mortality.
Cytokine and TCC levels were dynamic in the clinical course of CAP, with highest levels seen at admission for most mediators. Admission levels of cytokines and TCC did not differ between groups of microbial aetiology. High admission levels of IL-6 (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.18-1.84, P = .001), IL-8 (OR 1.79, 95% CI 1.26-2.55, P = .001) and MIP-1ß (OR 2.28, 95% CI 1.36-3.81, P = .002) were associated with a CURB-65 severity score of =3, while IL-6 (OR 1.37, 95% CI 1.07-1.74, P = .011) and MIP-1ß (OR 1.86, 95% CI 1.03-3.36, P = .040) were associated with a high risk of an adverse short-term outcome.
In this CAP cohort, admission levels of IL-6, IL-8 and MIP-1ß were associated with disease severity and/or adverse short-term outcome. Still, for most mediators, only nonsignificant variations in inflammatory responses were observed for groups of microbial aetiology, disease severity and short-term outcome.
Cites: PLoS One. 2016 Feb 05;11(2):e0148741 PMID 26849359
Cites: Crit Care Med. 2011 Oct;39(10 ):2211-7 PMID 21705887
Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown.
In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8 ± 4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression.
No significant difference in CAV progression was evident between the treatment groups (P = 0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n = 39), CAV progression was attenuated with everolimus versus standard CNI (?maximal intimal thickness 0.00 ± 0.04 and 0.04 ± 0.04 mm, ?percent atheroma volume 0.2% ± 3.0% and 2.6% ± 2.5%, and ?total atheroma volume 0.25 ± 14.1 and 19.8 ± 20.4 mm(3), respectively [P
To investigate serum levels of endostatin in a well characterised cohort of patients with primary Sjögren's syndrome (pSS) and healthy controls (HC) and assess associations between these mediators and clinical parameters.
All patients (n=144) were recruited from the Norwegian systemic connective tissue disease and vasculitis registry (NOSVAR) and fulfilled American-European classification criteria for pSS. Pulmonary involvement was based on clinical symptoms and abnormal findings on high-resolution computed tomography of the lungs. The controls were 100 healthy blood donors. Serum levels of endostatin was determined by enzyme immunoassay.
We found higher mean levels of serum endostatin in patients with pSS compared with the controls (p
There is a need to determine biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC). We evaluated the prognostic utility of the enhanced liver fibrosis (ELF) score in Norwegian PSC patients. Serum samples were available from 305 well-characterized large-duct PSC patients, 96 ulcerative colitis patients, and 100 healthy controls. The PSC patients constituted a derivation panel (recruited 1992-2006 [n?=?167]; median age 41 years, 74% male) and a validation panel (recruited 2008-2012 [n?=?138]; median age 40 years, 78% male). We used commercial kits to analyze serum levels of hyaluronic acid, tissue inhibitor of metalloproteinases-1, and propeptide of type III procollagen and calculated ELF scores by the previously published algorithm. Results were also validated by analysis of ELF tests using the ADVIA Centaur XP system and its commercially available reagents. We found that PSC patients stratified by ELF score tertiles exhibited significantly different transplant-free survival in both panels (P?
Despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields.
267 CAP patients were enrolled consecutively over our 3-year prospective study. Conventional methods (i.e., bacterial cultures, urinary antigen assays, serology) were combined with nasopharyngeal (NP) and oropharyngeal (OP) swab samples analyzed by real-time quantitative PCR (qPCR) for Streptococcus pneumoniae, and by real-time PCR for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis and 12 types of respiratory viruses.
Etiology was established in 167 (63%) patients with 69 (26%) patients having =1 copathogen. There were 75 (28%) pure bacterial and 41 (15%) pure viral infections, and 51 (19%) viral-bacterial coinfections, resulting in 126 (47%) patients with bacterial and 92 (34%) patients with viral etiology. S. pneumoniae (30%), influenza (15%) and rhinovirus (12%) were most commonly identified, typically with =1 copathogen. During winter and spring, viruses were detected more frequently (45%, P=.01) and usually in combination with bacteria (39%). PCR improved diagnostic yield by 8% in 64 cases with complete sampling (and by 15% in all patients); 5% for detection of bacteria; 19% for viruses (P=.04); and 16% for detection of =1 copathogen. Etiology was established in 79% of 43 antibiotic-naive patients with complete sampling. S. pneumoniae qPCR positive rate was significantly higher for OP swab compared to NP swab (P
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Cites: Clin Infect Dis. 2008 May 15;46(10):1513-2118419484