Beneficial Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients with Type 2 Diabetes Mellitus: Analysis of Responders and Non-Responders.

Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1, 32, and 52 weeks post-implant following a mixed meal tolerance test. Lipoprotein subclasses were analysed by proton nuclear magnetic resonance (1H NMR) spectrometry. DJBL provoked weight loss, a decrease in fat mass, and an improvement in insulin resistance and hepatic function in most but not all of the patients, but in the long term did not increase gut hormone fasting levels pointing to a combined effect of more than gut parameters alone. Lipidome analysis was done in 10 patients, allowing classification to responders and non-responders by reduction of sLDL-p subfraction; and to further analyse the atherogenic profile. Responders showed an overall more pronounced effect regarding improvement of HbA1c, BMI, and HOMA index.Implantation of a DJBL in obese type 2 diabetes patients does not per se lead to an improvement of the metabolic situation. Further analyses including larger cohorts have to be performed to identify responding patients, to better treat non-responders and to analyse the key effectors.

Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.