Cohort profile: 'Biomarkers of Personalised Medicine' (BioPersMed): a single-centre prospective observational cohort study in Graz/Austria to evaluate novel biomarkers in cardiovascular and metabolic diseases.

PURPOSE: Accumulating evidence points towards a close relationship between cardiovascular, endocrine and metabolic diseases. The BioPersMed Study (Biomarkers of Personalised Medicine) is a single-centre prospective observational cohort study with repetitive examination of participants in 2-year intervals. The aim is to evaluate the predictive impact of various traditional and novel biomarkers of cardiovascular, endocrine and metabolic pathways in asymptomatic individuals at risk for cardiovascular and/or metabolic disease. PARTICIPANTS: Between 2010 and 2016, we recruited 1022 regional individuals into the study. Subjects aged 45 years or older presenting with at least one traditional cardiovascular risk factor or manifest type 2 diabetes mellitus (T2DM) were enrolled. The mean age of the participants was 57±8 years, 55% were female, 18% had T2DM, 33% suffered from arterial hypertension, 15% were smokers, 42% had hyperlipidaemia, and only 26% were at low cardiovascular risk according to the Framingham 'Systematic COronary Risk Evaluation'. FINDINGS TO DATE: Study procedures during screening and follow-up visits included a physical examination and comprehensive cardiovascular, endocrine, metabolic, ocular and laboratory workup with biobanking of blood and urine samples. The variety of assessed biomarkers allows a full phenotyping of individuals at cardiovascular and metabolic risk. Preliminary data from the cohort and relevant biomarker analyses were already used as control population for genomic studies in local and international research cooperation. FUTURE PLANS: Participants will undergo comprehensive cardiovascular, endocrine and metabolic examinations for the next decades and clinical outcomes will be adjudicated prospectively.

Impact of Duodeno-Jejunal Bypass Liner (EndoBarrierTM) Implantation on Insulin Sensitivity in Patients with Type 2 Diabetes Mellitus (T2DM): A Study Protocol for a Pilot Trial.

INTRODUCTION: A 60-cm endoscopically implantable duodenal-jejunal bypass liner (Endobarrier™, GI Dynamics, Lexington, MA, USA) has been introduced as a therapeutic option to support weight loss for a selected group of obese subjects with type 2 diabetes mellitus (T2DM). The sleeve prevents contact between chyme and the intestinal mucosa of the upper gastrointestinal tract. The primary aim of this study is to elucidate the changes in insulin sensitivity and beta-cell function after EndoBarrier™ implantation in obese patients with T2DM; changes in gut permeability and gut microbiome are also to be examined. METHODS: This is an open, single-center, prospective trial in which ten obese subjects with T2DM and suboptimal glycemic control (glycosylated hemoglobin A1c (HbA1c) level > 48 mmol/mol) are investigated with regards to EndoBarrier™ implantation. The Endobarrier™ is implanted shortly after baseline and left in situ for a period of 36 weeks. Dual-energy X-ray absorptiometry measurement, assessment of beta-cell function and insulin sensitivity as measured by a Botnia clamp procedure, and a mixed-meal tolerance test are performed prior to implantation and at 4, 36, and 64 weeks after implantation. The composition of the gut microbiota is characterized from stool using 454 pyrosequencing of 16S rRNA genes. Gut permeability is assessed by a differential sugar absorption method. PLANNED OUTCOME: This study will give mechanistic insights in particulr into changes of insulin sensitivity, beta-cell function or microbiome changes over time in subjects implanted with an EndobarrierTM device. TRIAL REGISTRATION: NCT02769728, Registered 12 May 2016. Current Protocol Date/Version: 04 September 2017/Version 1.9.

Combined serum free light chain levels are associated with carotid atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus face an increased risk of cardiovascular events compared to non-diabetic counterparts. Chronic inflammation and activation of the immune system, including B-lymphocyte maturation is believed to play a role in atherosclerosis. Recent investigations suggest combined serum free light chains as a potential biomarker for cardiovascular events. The aim of this analysis was to investigate the association of combined serum free light chain with carotid atherosclerosis in subjects with type 2 diabetes mellitus. METHODS: We performed a cross-sectional analysis of data from a prospective single centre 2-year study of 97 patients with type 2 diabetes mellitus and insufficiently controlled cardiovascular risk factors. Complete data on combined serum free light chain, high-sensitivity C-reactive protein were available for 75 subjects. RESULTS: We analysed data of 26 female and 49 male subjects, aged 59 ± 8 years. Their mean body mass index was 31.6 ± 4.4 kg/m2, and the median B-score was 2 (interquartile range: 0-3). Significant positive correlations between combined serum free light chain and the B-score ( r = 0.38; p = 0.001) as well as combined serum free light chain and high-sensitivity C-reactive protein ( r = 0.35; p = 0.002) were observed. The adjusted odds ratio for a half standard deviation increase in combined serum free light chain was 1.48 (95% confidence interval: 1.05-2.05) in an ordinal regression model for carotid B-score. CONCLUSION: In our study, combined serum free light chain was associated with carotid atherosclerosis in subjects with type 2 diabetes mellitus.