Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is an incretin hormone, which gets secreted in response to nutritional stimuli from the gut mediating glucose-dependent insulin secretion. Interestingly, GLP-1 was recently found to be also increased in response to inflammatory stimuli in an interleukin 6 (IL-6) dependent manner in mice. The relevance of this finding to humans is unknown but has been suggested by the presence of high circulating GLP-1 levels in critically ill patients that correlated with markers of inflammation. This study was performed to elucidate, whether a direct link exists between inflammation and GLP-1 secretion in humans. RESEARCH DESIGN AND METHODS: We enrolled 22 non-diabetic patients scheduled for cardiac surgery as a reproducible inflammatory stimulus with repeated blood sampling before and after surgery. RESULTS: Mean total circulating GLP-1 levels significantly increased in response to surgery from 25.5 ± 15.6 pM to 51.9 ± 42.7 pM which was not found in a control population. This was preceded by an early rise of IL6, which was significantly associated with GLP-1 under inflammatory but not basal conditions. Using repeated measure ANCOVA, IL6 best predicted the observed kinetics of GLP-1, followed by blood glucose concentrations and cortisol plasma levels. Furthermore, GLP-1 plasma concentrations significantly predicted endogenous insulin production as assessed by C-peptide concentrations over time, while an inverse association was found for insulin infusion rate. CONCLUSION: We found GLP-1 secretion to be increased in response to inflammatory stimuli in humans, which was associated to parameters of glucose metabolism and best predicted by IL6.

Circulating concentrations of GLP-1 are associated with coronary atherosclerosis in humans.

BACKGROUND: GLP-1 is an incretine hormone which gets secreted from intestinal L-cells in response to nutritional stimuli leading to pancreatic insulin secretion and suppression of glucagon release. GLP-1 further inhibits gastric motility and reduces appetite which in conjunction improves postprandial glucose metabolism. Additional vasoprotective effects have been described for GLP-1 in experimental models. Despite these vasoprotective actions, associations between endogenous levels of GLP-1 and cardiovascular disease have yet not been investigated in humans which was the aim of the present study. METHODS: GLP-1 serum levels were assessed in a cohort of 303 patients receiving coronary CT-angiography due to typical or atypical chest pain. RESULTS: GLP-1 was found to be positively associated with total coronary plaque burden in a fully adjusted model containing age, sex, BMI, hypertension, diabetes mellitus, smoking, triglycerides, LDL-C (low density lipoprotein cholesterol), hsCRP (high-sensitive C-reactive protein), and eGFR (estimated glomerular filtration rate) (OR: 2.53 (95% CI: 1.12 - 6.08; p = 0.03). CONCLUSION: Circulating GLP-1 was found to be positivity associated with coronary atherosclerosis in humans. The clinical relevance of this observation needs further investigations.

Sixteen-week multicentre randomised controlled trial to study the effect of the consumption of an oat beta-glucan-enriched bread versus a whole-grain wheat bread on glycaemic control among persons with pre-diabetes: a study protocol of the CarbHealth study.

INTRODUCTION: In 2012, the estimated global prevalence of pre-diabetes was 280 million, and the prevalence is expected to rise to 400 million by 2030. Oat-based foods are a good source of beta-glucans, which have been shown to lower postprandial blood glucose. Studies to evaluate the effectiveness of the long-term intake of beta-glucan-enriched bread as part of a habitual diet among individuals with pre-diabetes are needed. Therefore, we designed a multicentre intervention study in adults with pre-diabetes to investigate the effects of consumption of an oat-derived beta-glucan-enriched bread as part of a normal diet on glycated haemoglobin (HbA1c) in comparison to consumption of whole-grain wheat bread. METHODS AND ANALYSIS: The CarbHealth trial is a multicentre double-blind randomised controlled 16-week dietary intervention trial in participants 40-70 years of age with a body mass index of ≥27 kg/m2 and HbA1c of 35-50 mmol/mol. The study is conducted at four universities located in Norway, Sweden and Germany and uses intervention breads specifically designed for the trial by Nofima AS. The aim is to recruit 250 participants. The primary outcome is the difference in HbA1c between the intervention and the control groups. The main analysis will include intervention group, study centre and baseline HbA1c as independent variables in an analysis of covariance model. ETHICS AND DISSEMINATION: The study protocol was approved by respective ethical authorities in participating countries. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT04994327.

Paraplegia prevention in aortic aneurysm repair by thoracoabdominal staging with 'minimally invasive staged segmental artery coil embolisation' (MIS²ACE): trial protocol for a randomised controlled multicentre trial.

INTRODUCTION: Spinal cord injury (SCI) including permanent paraplegia constitutes a common complication after repair of thoracoabdominal aortic aneurysms. The staged-repair concept promises to provide protection by inducing arteriogenesis so that the collateral network can provide a robust blood supply to the spinal cord after intervention. Minimally invasive staged segmental artery coil embolisation (MIS2ACE) has been proved recently to be a feasible enhanced approach to staged repair. METHODS AND ANALYSIS: This randomised controlled trial uses a multicentre, multinational, parallel group design, where 500 patients will be randomised in a 1:1 ratio to standard aneurysm repair or to MIS2ACE in 1-3 sessions followed by repair. Before randomisation, physicians document whether open or endovascular repair is planned. The primary endpoint is successful aneurysm repair without substantial SCI 30 days after aneurysm repair. Secondary endpoints include any form of SCI, mortality (up to 1 year), length of stay in the intensive care unit, costs and quality-adjusted life years. A generalised linear mixed model will be used with the logit link function and randomisation arm, mode of repair (open or endovascular repair), the Crawford type and the European System for Cardiac Operative Risk Evaluation (euroSCORE) II as fixed effects and the centre as a random effect. Safety endpoints include kidney failure, respiratory failure and embolic events (also from debris). A qualitative study will explore patient perceptions. ETHICS AND DISSEMINATION: This trial has been approved by the lead Ethics Committee from the University of Leipzig (435/17-ek) and will be reviewed by each of the Ethics Committees at the trial sites. A dedicated project is coordinating communication and dissemination of the trial. TRIAL REGISTRATION NUMBER: NCT03434314.

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial.

BACKGROUND: Walnut consumption is associated with reduced risk of coronary heart disease (CHD). OBJECTIVE: We assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old. DESIGN: Forty subjects (mean±SEM: age 60±1years, BMI 24.9±0.6kg/m(2); 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment×time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin. RESULTS: Compared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: -10±3 vs. -3±2mg/dL; p=0.025) and apolipoprotein-B (-5.0±1.3 vs. -0.2±1.1mg/dL; p=0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p=0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected. CONCLUSION: Daily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk.