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Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention.

Non-diabetic children with multiple islet autoantibodies were recruited to a secondary prevention trial. The objective was to determine the predictive value of baseline (1) HbA1c and metabolic variables derived from intravenous (IvGTT) and oral glucose tolerance tests (OGTT), (2) insulin resistance and (3) number, type and levels of islet autoantibodies, for progression to type 1 diabetes.

The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol

Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret resu

The impact of low-frequency and rare variants on lipid levels.

Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs w

GPR40 protein levels are crucial to the regulation of stimulated hormone secretion in pancreatic islets. Lessons from spontaneous obesity-prone and non-obese type 2 diabetes in rats.

The role of islet GPR40 protein in the pathogenesis of diabetes is unclear. We explored the influence of GPR40 protein levels on hormone secretion in islets from two rat models of spontaneous type 2 diabetes displaying either hyperlipidaemia or hyperglycaemia. GPR40 expression was analysed by confocal microscopy, Western blot and qPCR in islets from preobese Zucker (fa/fa) rats, diabetic Goto-Kaki

HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13

Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD <= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Sc

A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells.

Signalling through gap junctions contributes to control insulin secretion and, thus, blood glucose levels. Gap junctions of the insulin-producing β-cells are made of connexin 36 (Cx36), which is encoded by the GJD2 gene. Cx36-null mice feature alterations mimicking those observed in type 2 diabetes (T2D). GJD2 is also expressed in neurons, which share a number of common features with pancreatic β-

Adsorption of low-density lipoprotein, its oxidation, and subsequent binding of specific recombinant antibodies-an in situ ellipsometric study.

BACKGROUND: Low-density lipoprotein (LDL) particles accumulate in the arterial wall and become oxidized during atherogenesis, leading to the formation of atherosclerotic plaques. The major protein of the LDL particle, apolipoprotein B-100 (apoB-100), becomes fragmented during oxidation and a target for the immune system. METHODS: In this study we used in situ ellipsometry to monitor the adsorption

Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to ide

Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes

Genome sequencing can identify individuals in the general population who harbor rare coding variants in genes for Mendelian disorders1-7 and who may consequently have increased disease risk. Previous studies of rare variants in phenotypically extreme individuals display ascertainment bias and may demonstrate inflated effect-size estimates8-12. We sequenced seven genes for maturity-onset diabetes o

Female hairdressers - Respiratory symptoms, mechanisms, and health-related quality of life and their views on the work environment

Popular Abstract in Swedish Frisöryrket har en lång historia av stolta yrkesutövare, men frisörer arbetar i en komplex arbetsmiljö, där de utsätts för olika risker, inte bara luftvägsbesvär, utan även handeksem, muskelrelaterade besvär, stress, och ögonbesvär. I Sverige är 85 - 90 % av frisörerna kvinnor, varav de flesta är egenföretagare antingen som ensamägare till en salong eller tillsammans meLittle is known of respiratory symptoms in female hairdressers, and of the impact on the health-related quality of life (HRQoL), nor of knowledge of their own views on preventive work. The aim of this thesis was to examine the occurrence of asthma, symptoms and mechanism of bleaching-associated nasal symptoms, the effects on HRQoL and how young hairdressers reason about the work environment. A m

Between-Monitor Differences in Step Counts Are Related to Body Size: Implications for Objective Physical Activity Measurement

Background: The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation. Methods: Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day du

Regulation of core clock genes in human islets.

Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS-We have conducted a meta-analysis of genome-wide as

Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program

OBJECTIVE Over 30 loci have been associated with risk of type 2 diabetes at genome-wide statistical significance. Genetic risk scores (GRSs) developed from these loci predict diabetes in the general population. We tested if a GRS based on an updated list of 34 type 2 diabetes-associated loci predicted progression to diabetes or regression toward normal glucose regulation (NGR) in the Diabetes Prev

Association between plasma leptin and blood pressure in two population-based samples of children and adolescents

Objectives In this study we examined the association between leptin and blood pressure in a population-based study of Danish and Norwegian children and adolescents. Because of the putative bidirectional relationship between leptin and adiposity we formally tested (i) the mediating effect of body mass index in the association between leptin and blood pressure, and (ii) the mediating effect of lepti

Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program

Andersson U, Henriksson E, Strom K, Alenfall J, Goransson O, Holm C. Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program. Am J Physiol Endocrinol Metab 300: E111-E121, 2011. First published October 19, 2010; doi:10.1152/ajpendo.00268.2010.-The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered ro