Peripheral Mononuclear Cell Resistin mRNA Expression Is Increased in Type 2 Diabetic Women

Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 were all significantly higher in DM2 compared to control women (P < .001). The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1β, TNF-α, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients

Blood-based analysis of type-2 diabetes mellitus susceptibility genes identifies specific transcript variants with deregulated expression and association with disease risk

Despite significant progress by genome-wide association studies, the ability of genetic variants to conduce to the prediction or prognosis of type-2 diabetes (T2D) is weak. Expression analysis of the corresponding genes may suggest possible links between single-nucleotide polymorphisms and T2D phenotype and/or risk. Herein, we investigated the expression patterns of 24 T2D-susceptibility genes, and their individual transcript variants (tv), in peripheral blood of T2D patients and controls (CTs), applying RNA-seq and real-time qPCR methodologies, and explore possible associations with disease features. Our data revealed the deregulation of certain transcripts in T2D patients. Among them, the down-regulation of CAPN10 tv3 was confirmed as an independent predictor for T2D. In patients, increased expression of CDK5 tv2, CDKN2A tv3 or THADA tv5 correlated positively with serum insulin levels, of CDK5 tv1 positively with % HbA1c levels, while in controls, elevated levels of TSPAN8 were associated positively with the presence of T2D family history. Herein, a T2D-specific expression profile of specific transcripts of disease-susceptibility genes is for the first time described in human peripheral blood. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers

A Case of Meningococcal and HSV-2 Meningitis in a Patient Being Treated with Ustekinumab for Pityriasis Rubra Pilaris

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous dermatosis affecting both adults and children. Six subtypes of PRP have been described. Recently, the management of PRP with biologic immunosuppressive agents regularly used in psoriasis has been supported by several case reports and series. Ustekinumab is an anti-IL12/23 IgG1 kappa human monoclonal antibody. It has been approved for the treatment of Crohn’s disease, plaque psoriasis, psoriatic arthritis and ulcerative colitis. It has also been reported to be effective as an off-label treatment for PRP. Current data are equivocal regarding infectious disease risk with ustekinumab administration. We describe a case of meningococcal and HSV-2 infection of the central nervous system in a patient being treated with ustekinumab for PRP

Toll/Interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction

<p>Abstract</p> <p>Background</p> <p>Soluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c.</p> <p>Methods</p> <p>158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction < 50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis).</p> <p>Results</p> <p>Patients with type 2 diabetes with (p < 0.001) or without LVDD (p = 0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p = 0.213 & p = 0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p = 0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes.</p> <p>Conclusions</p> <p>Patients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.</p

FOLLOW UP OF FLUCTATIONS OF 14C-AMINOPYRINE BREATH TEST IN DIABETIC PATIENTS INRELATION TO THE DEGREE AND TYPE OF BLOOD GLUCOSE CONTROL

WE HAVE MEASURED THE CUMULATIVE ELIMINATION RATE OF 14CO2, EXPRESSED AS THE PERCENT RATIO OF INGESTED C-14-LABELED AMINOPYRINE, EXHALED OVER A PERIOD OF 2 HOURS, IN 45 DIABETIC PATIENTS, DIVIDED IN 3 GROUPS DEPENDING ON THE TREATMENT FOR THE DIABETES. THE 14C-AMINOPYRINE BREATH TEST WAS PERFORMED AT A FIRST PHASETHAT DIABETES WAS POORLY CONTROLLED AND AT A SECOND PHASE THAT IT WAS WELL CONTROLLED. THE RESULTS INDICATE THAT: 1) A STATISTICALLY SIGNIFICANT DECREASE OF THE CUMULATIVE PERCENTAGE OF 14CO2 EXHALED WAS OBSERVED IN ALL 3 GROUPS AT THE PHASE OF WELL CONTROLLED DIABETIC CONDITION. 2) DIABETIC PATIENTS TREATED WITH DIET ALONE PRESENTED THE HIGHEST, WHILE THOSE TREATED WITH INSULIN ELIMINATED THE LESS CUMULATIVE PERCENTAGE OF 14CO2. IT IS CONCLUDED THAT THE STATE OFINSULIN DEFICIENCY AFFECTS THE HEPATIC CYTOCHROME P.450 ENZYME ACTIVITIES ANDTHAT THE POORLY CONTROLLED DIABETES MELLITUS CONDUCTS TO AN INDUCTION OF P.450 ENZYME ACTIVITIES RESULTING IN DEFECTIVE DRUG HEPATIC METABOLISM.ΣΕ 45 ΔΙΑΒΗΤΙΚΟΥΣ ΑΣΘΕΝΕΙΣ, ΚΑΤΑΝΕΜΗΜΕΝΟΥΣ ΑΝΑ 15 ΣΕ 3 ΟΜΑΔΕΣ, ΑΝΑΛΟΓΩΣ ΤΗΣ ΑΝΤΙΔΙΑΒΗΤΙΚΗΣ ΑΓΩΓΗΣ, ΜΕΤΡΗΘΗΚΕ ΤΟ ΠΟΣΟΣΤΟ ΤΟΥ ΣΥΝΟΛΙΚΑ ΕΚΠΝΕΟΜΕΝΟΥ 14CO2, ΕΦΑΡΜΟΖΟΝΤΑΣ ΤΗΝ ΑΝΑΠΝΕΥΣΤΙΚΗ ΔΟΚΙΜΑΣΙΑ ΜΕ 14C-ΑΜΙΝΟΠΥΡΙΝΗ. ΚΑΘΕ ΟΜΑΔΑ ΚΑΙ ΚΑΘΕ ΑΣΘΕΝΕΙΣ (ΩΣ ΜΑΡΤΥΡΑΣ ΤΟΥ ΕΑΥΤΟΥ ΤΟΥ) ΕΛΕΓΧΘΗΚΕ ΚΑΙ ΣΥΓΚΡΙΘΗΚΕ ΣΕ "ΚΑΚΗ" ΚΑΙ "ΚΑΛΗ" ΜΕΤΑΒΟΛΙΚΗ ΡΥΘΜΙΣΗ, ΠΡΟΚΕΙΜΕΝΟΥ ΝΑ ΔΙΑΠΙΣΤΩΘΕΙ ΕΑΝ Η ΜΕΤΑΒΟΛΙΚΗ ΕΚΤΡΟΠΗ ΕΠΗΡΕΑΖΕΙ ΤΗΝ ΑΝΑΠΝΕΥΣΤΙΚΗ ΔΟΚΙΜΑΣΙΑ, ΑΡΑ ΤΗ ΔΡΑΣΤΗΡΙΟΤΗΤΑ ΤΟΥ ΕΝΖΥΜΙΚΟΥ ΣΥΣΤΗΜΑΤΟΣ ΤΟΥ ΚΥΤΟΧΡΩΜΑΤΟΣ P.450. ΠΑΡΑΤΗΡΗΘΗΚΕ 1) ΣΤΑΤΙΣΤΙΚΑ ΣΗΜΑΝΤΙΚΗ ΠΤΩΣΗ ΤΟΥ ΠΟΣΟΣΤΟΥ ΤΟΥ ΣΥΝΟΛΙΚΑ ΕΚΠΝΕΟΜΕΝΟΥ 14CO2 ΚΑΙ ΣΤΙΣ 3 ΟΜΑΔΕΣ ΑΣΘΕΝΩΝ ΣΤΗΝ "ΚΑΛΗ" ΜΕΤΑΒΟΛΙΚΗ ΡΥΘΜΙΣΗ, 2) ΟΙ ΔΙΑΒΗΤΙΚΟΙ ΥΠΟ ΔΙΑΙΤΑ ΕΝΕΦΑΝΙΣΑΝ ΤΟ ΥΨΗΛΟΤΕΡΟ ΠΟΣΟΣΤΟ ΕΚΠΝΕΟΜΕΝΟΥ 14CO2 ΚΑΙ ΟΙ ΔΙΑΒΗΤΙΚΟΙ ΥΠΟ ΙΝΣΟΥΛΙΝΗ ΤΟ ΧΑΜΗΛΟΤΕΡΟ. ΔΙΑΠΙΣΤΩΘΗΚΕ ΟΤΙΗ ΚΑΤΑΣΤΑΣΗ ΤΗΣ "ΙΝΣΟΥΛΙΝΟΠΕΝΙΑΣ" ΕΠΗΡΕΑΖΕΙ ΤΗΝ ΕΝΖΥΜΙΚΗ ΔΡΑΣΤΗΡΙΟΤΗΤΑ ΤΟΥ P.450 ΚΑΙ Η "ΚΑΚΗ" ΜΕΤΑΒΟΛΙΚΗ ΡΥΘΜΙΣΗ ΤΟΥ ΔΙΑΒΗΤΙΚΟΥ ΕΠΑΓΕΙ ΤΑ ΕΝΖΥΜΑ ΤΟΥ P.450,ΟΔΗΓΩΝΤΑΣ ΣΕ ΠΛΗΜΜΕΛΗ ΜΕΤΑΒΟΛΙΣΜΟ ΤΩΝ ΦΑΡΜΑΚΩΝ ΣΤΟ ΗΠΑΡ

High Insulin and Leptin Increase Resistin and Inflammatory Cytokine Production from Human Mononuclear Cells

Resistin and the proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF-α, IL-6, and IL-1β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF-α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1β production. By comparison, exposure to dexamethasone reduced TNF-α, IL-6, and IL-1β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF-α, IL-6, and IL-1β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients

Peripheral Mononuclear Cell Resistin mRNA Expression Is Increased in Type 2 Diabetic Women

Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-6 were all significantly higher in DM2 compared to control women (P &lt; .001). The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1 beta, TNF-alpha, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients. Copyright (C) 2008 Panayoula C. Tsiotra et al