High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

Peer reviewe

The majority of type 2 diabetic patients in Finnish primary care are at very high risk of cardiovascular events : A cross-sectional chart review study (STONE HF)

Publisher Copyright: © 2021 The AuthorsAims: To characterize clinical profiles, prevalence of chronic kidney disease (CKD), and treatment patterns in type 2 diabetes (T2D) and heart failure (HF) patients in Finnish primary care. Methods: A total of 1385 patients (1196 with T2D, 50 with HF, and 139 with T2D and HF) in 60 Finnish primary care centers were recruited to this cross-sectional study. Data on demographic and clinical characteristics, laboratory measurements, and medications were collected retrospectively from medical records. T2D patients were classified according to their risk of cardiovascular (CV) events as very high-risk (62%) and other patients (38%). Results: Of the T2D patients, 10% (139/1335) had a diagnosis of HF and 42% (457/1090) had stage 3–5 CKD and/or albuminuria based on laboratory measurement. Of the HF patients, 74% (139/189) had T2D and 78% (114/146) had stage 3–5 CKD and/or albuminuria. Metformin was the most frequently used medication in both very high-risk patients (74%) and other patients (86%). SGLT2 inhibitors and/or GLP-1 analogues were used by 37% of very high-risk patients compared to 42% in other patients. Conclusions: The majority of T2D patients in Finnish primary care are at very high risk of cardiovascular events. However, the implementation of treatments with proven cardioprotective effects in very high-risk patients is currently suboptimal.Peer reviewe

Tyypin 2 diabeteksen hoitosuunnitelmissa ja hoidon kohdentamisessa on parantamisen varaa

Lähtökohdat : Tyypin 2 diabeteksen hoidon keskeisiä tavoitteita ovat taudin etenemisen hidastaminen ja hyvä elämänlaatu. Hoidon tueksi tehdään hoitosuunnitelma, joka auttaa toimenpiteiden kohdentamisessa potilaan tarpeiden mukaan. Hoitosuunnitelman toteutumista Suomessa ei ole tutkittu. Menetelmät :Tässä kyselytutkimuksessa kerättiin tietoa tyypin 2 diabetesta sairastavien lääkityksestä, liitännäissairauksista, hoitosuunnitelmasta ja hoidon tavoitteiden sisäistämisestä. Osallistujiksi pyydettiin diabeteslääkityksenään muuta kuin pelkästään insuliinia käyttäneitä avoapteekkien asiakkaita. Tulokset : Kyselyyn vastasi 1 067 diabetespotilasta. Heistä 70 % oli osallistunut hoitonsa suunnitteluun, 63 % koki saaneensa hoitosuunnitelmasta tukea, mutta vain 35 % kertoi saaneensa suunnitelman kirjallisena. Hyödyt toteutuivat pienillä paikkakunnilla useammin kuin suurilla. Kirjallinen suunnitelma oli yhteydessä hoitotavoitteiden parempaan ymmärtämiseen. Sydän- ja verisuoni tautiriski ei vaikuttanut käyntitiheyteen (53–55 % vastaanotolla alle 6 kk aiemmin). Vain puolet riskipotilaista käytti uusia ennusteeseen vaikuttavia diabeteslääkkeitä. Päätelmät : Diabeteksen kirjallista hoitosuunnitelmaa käytetään riittämättömästi. Resurssien ja hoidon parempi kohdentaminen potilaan tarpeiden mukaan olisi sekä kansanterveydellisesti että kansantaloudellisesti järkevää.Peer reviewe

The majority of type 2 diabetic patients in Finnish primary care are at very high risk of cardiovascular events: A cross-sectional chart review study (STONE HF).

AimsTo characterize clinical profiles, prevalence of chronic kidney disease (CKD), and treatment patterns in type 2 diabetes (T2D) and heart failure (HF) patients in Finnish primary care.MethodsA total of 1385 patients (1196 with T2D, 50 with HF, and 139 with T2D and HF) in 60 Finnish primary care centers were recruited to this cross-sectional study. Data on demographic and clinical characteristics, laboratory measurements, and medications were collected retrospectively from medical records. T2D patients were classified according to their risk of cardiovascular (CV) events as very high-risk (62%) and other patients (38%).ResultsOf the T2D patients, 10% (139/1335) had a diagnosis of HF and 42% (457/1090) had stage 3-5 CKD and/or albuminuria based on laboratory measurement. Of the HF patients, 74% (139/189) had T2D and 78% (114/146) had stage 3-5 CKD and/or albuminuria. Metformin was the most frequently used medication in both very high-risk patients (74%) and other patients (86%). SGLT2 inhibitors and/or GLP-1 analogues were used by 37% of very high-risk patients compared to 42% in other patients.ConclusionsThe majority of T2D patients in Finnish primary care are at very high risk of cardiovascular events. However, the implementation of treatments with proven cardioprotective effects in very high-risk patients is currently suboptimal.</p

Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults—Randomized Controlled Trial

Abstract The gut microbiota is interlinked with obesity, but direct evidence of effects of its modulation on body fat mass is still scarce. We investigated the possible effects of Bifidobacterium animalis ssp. lactis 420 (B420) and the dietary fiber Litesse® Ultra polydextrose (LU) on body fat mass and other obesity-related parameters. 225 healthy volunteers (healthy, BMI 28–34.9) were randomized into four groups (1:1:1:1), using a computer-generated sequence, for 6months of double-blind, parallel treatment: 1) Placebo, microcrystalline cellulose, 12g/d; 2) LU, 12g/d; 3) B420, 1010CFU/d in microcrystalline cellulose, 12g/d; 4) LU+B420, 12g+1010CFU/d. Body composition was monitored with dual-energy X-ray absorptiometry, and the primary outcome was relative change in body fat mass, comparing treatment groups to Placebo. Other outcomes included anthropometric measurements, food intake and blood and fecal biomarkers. The study was registered in Clinicaltrials.gov (NCT01978691). There were marked differences in the results of the Intention-To-Treat (ITT; n=209) and Per Protocol (PP; n=134) study populations. The PP analysis included only those participants who completed the intervention with >80% product compliance and no antibiotic use. In addition, three participants were excluded from DXA analyses for PP due to a long delay between the end of intervention and the last DXA measurement. There were no significant differences between groups in body fat mass in the ITT population. However, LU+B420 and B420 seemed to improve weight management in the PP population. For relative change in body fat mass, LU+B420 showed a−4.5% (−1.4kg, P=0.02, N=37) difference to the Placebo group, whereas LU (+0.3%, P=1.00, N=35) and B420 (−3.0%, P=0.28, N=24) alone had no effect (overall ANOVA P=0.095, Placebo N=35). A post-hoc factorial analysis was significant for B420 (−4.0%, P=0.002 vs. Placebo). Changes in fat mass were most pronounced in the abdominal region, and were reflected by similar changes in waist circumference. B420 and LU+B420 also significantly reduced energy intake compared to Placebo. Changes in blood zonulin levels and hsCRP were associated with corresponding changes in trunk fat mass in the LU+B420 group and in the overall population. There were no differences between groups in the incidence of adverse events. This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU+B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes.Peer reviewe

Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Contolled Trial

DiscussionThis clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU + B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes.</p

Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways

<p>Abstract</p> <p>Background</p> <p>Up-regulation of vascular endothelin type B (ET_B) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, <it>ex vivo</it>, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ET_Breceptors in human internal mammary arteries.</p> <p>Methods</p> <p>Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using <it>in vitro </it>pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET_Aand ET_Breceptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.</p> <p>Results</p> <p>The endohtelin-1-induced contraction (after endothelin ET_Breceptor desensitization) and the endothelin ET_Areceptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ET_Breceptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 μM bisindolylmaleimide I and 10 μM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 μM SB203580, 10 μM PD98059 and 10 μM SP600125, respectively).</p> <p>Conclusion</p> <p>In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ET_Breceptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ET_Breceptor changes in cardiovascular disease.</p

Tyypin 2 diabeteksen hoitosuunnitelmissa ja hoidon kohdentamisessa on parantamisen varaa

Lähtökohdat : Tyypin 2 diabeteksen hoidon keskeisiä tavoitteita ovat taudin etenemisen hidastaminen ja hyvä elämänlaatu. Hoidon tueksi tehdään hoitosuunnitelma, joka auttaa toimenpiteiden kohdentamisessa potilaan tarpeiden mukaan. Hoitosuunnitelman toteutumista Suomessa ei ole tutkittu. Menetelmät :Tässä kyselytutkimuksessa kerättiin tietoa tyypin 2 diabetesta sairastavien lääkityksestä, liitännäissairauksista, hoitosuunnitelmasta ja hoidon tavoitteiden sisäistämisestä. Osallistujiksi pyydettiin diabeteslääkityksenään muuta kuin pelkästään insuliinia käyttäneitä avoapteekkien asiakkaita. Tulokset : Kyselyyn vastasi 1 067 diabetespotilasta. Heistä 70 % oli osallistunut hoitonsa suunnitteluun, 63 % koki saaneensa hoitosuunnitelmasta tukea, mutta vain 35 % kertoi saaneensa suunnitelman kirjallisena. Hyödyt toteutuivat pienillä paikkakunnilla useammin kuin suurilla. Kirjallinen suunnitelma oli yhteydessä hoitotavoitteiden parempaan ymmärtämiseen. Sydän- ja verisuoni tautiriski ei vaikuttanut käyntitiheyteen (53–55 % vastaanotolla alle 6 kk aiemmin). Vain puolet riskipotilaista käytti uusia ennusteeseen vaikuttavia diabeteslääkkeitä. Päätelmät : Diabeteksen kirjallista hoitosuunnitelmaa käytetään riittämättömästi. Resurssien ja hoidon parempi kohdentaminen potilaan tarpeiden mukaan olisi sekä kansanterveydellisesti että kansantaloudellisesti järkevää.publishedVersionPeer reviewe

NMR METABOLOMICS AND PROTEOMICS ON CELL MONOLAYER STUDYING THE EFFECT OF SYMBIOTICS

Introduction: The gut microbiota has shown to be involved in changes of the body fat mass in humans. The aim of this study was to investigate if symbiotics may enhance the gut health benefit of pre- and probiotics. By growing a Caco-2 cell monolayer on permeable membranes in-vitro, the cell model can be used to mimic the small intestine epithelium. Stimulations were performed by adding selected fecal water samples from a large clinical trial on symbiotics to the apical side of the Caco-2 cell monolayer. To explore the mechanistic effects, NMR metabolomics was used to detect indirect effects of the Caco-2 cell monolayer and fecal water on the metabolic profiles of the cell media. Proteomics on the cells were carried out to determine if proteins were regulated by symbiotic treatment.Methods & Results: Stimulations were performed by adding fecal samples diluted in PBS and sterilized by filtration through a 0.22-micron filter from 26 subjects. The samples belong to 5 different groups: Placebo, A_responder, A_non-responder, A+B_responder, A+B_non-responder, where A+B is the symbiotic treatment. Caco-2 cells were seeded onto filter inserts and incubated in 24-well plates for 18 days. Stimulations were performed for 24 hours with 4 replicates. A hundred μL sterile fecal water and 300 μL cell media was added to the apical side. Four replicates of control samples on each plate were obtained by the addition of 400 μL cell media to the apical side. Cell media from the apical and basolateral sides are collected at the end of the intervention. CaCo-2 cells were harvested, lysed and digested.1H NMR spectra were recorded on a Bruker Avance III 600 MHz spectrometer equipped with a Prodigy CryoProbe using standard 1D NOESY experiments. The 1H NMR spectra were automatically aligned, phased and binned prior to being analyzed by multivariate statistics. Proteomics were performed by using a nanoflow-LC connected to an Orbitrap Fusion. Proteins were identified using SEQUES HT + Percolator and quantified label-free in GeneData Expressionist. Regulated proteins were analyzed by Ingenuity Pathway Analysis (IPA) software. Results in a total of 7057 proteins were identified using 1% false discovery rate (FDR). Statistical filtering of the preliminary quantitative results showed that 145 proteins were significantly regulated. Pathway analysis of regulated proteins in IPA, showed that several pathways were affected including inflammatory responses, immunological disease, and lipid metabolism. PCA analysis using the 145 proteins or the binned NMR spectra showed a weak tendency for subjects to separate between responders and non-responders in the group who received symbiotics.Conclusion: TEER measurements on the Caco-2 cell monolayer model indicate a stronger gut barrier integrity as an effect of the symbiotic group. Differences in the metabolic profiles was found on the apical side between symbiotic responder vs. non-responder groups. No clear metabolic effect of the caco-2 cell monolayer could be found. Proteomics suggests that the effect from the symbiotic treatment effects pathways involved in cell proliferation of gut epithelium cells and ion transport across the cell layer. Regulated pathways observed in this study needs to be further investigated for their relationship to a symbiotic diet