Health Related Quality of Life in Patients with Diabetes Mellitys Type I

Diabetes mellitus type I (DMT1 I is a chronic disease caused by the autoimmune destruction of the insulin-producing beta cells in the pancreas, resulting in an absolute inability to produce the hormone insulin which is necessary for the regulation of blood glucose levels. The autoimmune destruction is postulated to result from an interaction between genetic and environmental factors, with the latter triggering the onset of the disease in genetically susceptible individuals. Various theories explaining the pathogenesis have been proposed in which environmental agents may serve as modifiers of pathogenesis rather than as triggers. These environmental risk determinants may be classified into three groups: viral infections, early postnatal diet, and toxins. Other non-genetic disease modifying factors include vaccine administration, psychological stressors, and climatic influences. The incidence of DMT1 is rapidly increasing in many parts of the developed world, and is showing a trend toward earlier age of onset. The incidence of DMT1 is highly variable among different ethnic populations, occurring most frequently in persons of north European descent, diminishing in southern direction, the 'North-South gradient', with the notable exception of Sardinia. The incidence of DMT1 is projected to be approximately 40 percent higher in 2010 than it was in 1997. The prevalence in The Netherlands is 0.3 percent. Diabetes mellitus type I is characterized by hyperglycemia with the eventual development of micro- and macrovascular complications which define the degree of morbidity in these patients

General practice registration networks in the Netherlands: a brief report

In the Netherlands, several general practice registrations exist. Groups of general practitioners register elements of patient care according to agreed-upon criteria, and these data are collected in a central database. By means of a questionnaire the authors interviewed the managers of all nine computerized registration networks extensively about the possibilities and limitations of their registration. In addition, respondents answered some questions with data from the central database of their network. Various items are collected by nearly all the registration networks, while other items are collected by only one network. Answering questions with data from the central database turned out to be difficult. Organization and manpower are the main obstacles

Type 2 diabetes and COPD: treatment in the right healthcare setting?: An observational study

Background Type 2 diabetes (T2DM) and COPD are chronic medical conditions, for which patients need lifelong healthcare. The aim of this study is to examine in which healthcare setting patients with T2DM and COPD receive their care, and if this is the correct healthcare setting according to guidelines. Method T2DM and COPD patients from five primary care practices were included. Data concerning healthcare setting and patient- and clinical characteristics were extracted from the electronic medical records. Patient profiles treated in primary care were compared with the profiles of those treated in secondary care. In patients treated in secondary care we evaluated whether treatment allocation was according to the guidelines and if back-referral to primary care should take place. Results Of the T2DM and COPD patients 7.6% and 29.6% respectively, were treated in secondary care, and 72.7% respectively 31.4% of these were according to the guideline. T2DM patients treated in primary care were older (63 versus 57 years, p < 0.01, had a shorter diabetes duration (8 versus 11 years, p < 0.01) and lower HbA1c (53.0 versus 63.5 mmol/l, p < 0.01) than those treated in secondary care. Those with COPD treated in primary care used less inhalation medication (75.2 versus 90.1%, p < 0.01) and had better spirometry results (67.39 versus 57.53 FEV1%pred, p < 0.01). Conclusion The majority of the patients with T2DM and COPD were correctly treated in primary care and on average patients with a better health condition were treated in primary care.. Also, those who were treated in secondary care were most of the time treated in the correct treatment setting according to the guidelines.Prevention, Population and Disease management (PrePoD)Public Health and primary car

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362