Filtyp
Background There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease. We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D. Methods In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all
We previously showed that dietary sphingomyelin (SM) inhibited cholesterol absorption in animals. The key enzyme hydrolyzing SM in the gut is alkaline sphingomyelinase (alk-SMase, NPP7). Here using fecal dual-isotope ratio method we compared cholesterol absorption in the wild type (WT) and alk-SMase knockout (KO) mice. The animals were fed an emulsion containing (14)C-cholesterol and (3)H-sitoster
Folate plays an important role in the synthesis and methylation of DNA as a cofactor in one-carbon metabolism. Inadequate folate intake has been linked to adverse health events. However, comparable information on dietary folate intake across European countries has never been reported. The objective of the present study was to describe the dietary folate intake and its food sources in ten countries
BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in th
We have recently shown that 17β-estradiol (E2) and the synthetic G protein-coupled receptor 30 (GPR30) ligand G-1 have antiapoptotic actions in mouse pancreatic islets, raising the prospect that they might exert beneficial effects also in human islets. The objective of the present study was to identify the expression of GPR30 in human islets and clarify the role of GPR30 in islet hormone secretion
The single nucleotide polymorphism 1858C> T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR)
Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nut
Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have exami
Salt-inducible kinase (SIK) 3 is a virtually unstudied, ubiquitously expressed serine/threonine kinase, belonging to the AMP-activated protein kinase (AMPK)-related family of kinases, all of which are regulated by LKB1 phosphorylation of a threonine residue in their activation (T)-loops. Findings in adrenal cells have revealed a role for cAMP in the regulation of SIK1, and recent findings suggest
The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass surgery (GBP) is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10 kg equivalent weight l
Objective Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design Population-based case-control study Methods We used data from ESTRID case-control study carried out between
Previous global RNA analysis was restricted to known transcripts in species with a defined transcriptome. Next generation sequencing has transformed transcriptomics by making it possible to analyse expressed genes with an exon level resolution from any tissue in any species without any a priori knowledge of which genes that are being expressed, splice patterns or their nucleotide sequence. In addi
Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis, and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Islets from mice with pancre
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 commo
In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however the pathways governing this adaptive response are not entirely established. While the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates co
Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and a critical element of cholesterol metabolism. To better elucidate the role of apoA-I structure-function in cholesterol metabolism, the conformation of apoA-I's N-terminus (residues 6-98) on nascent HDL was examined by electron paramagnetic resonance (EPR) spectroscopic analysis. A series of 93 apoA-I
Objective Histological evaluation of intestinal biopsies for the diagnosis of coeliac disease can be challenging and compatible with risk of misdiagnosis. The aim was to evaluate the agreement of pathological diagnosis for coeliac disease in children investigated at four major paediatric university hospitals in Sweden. Materials and methods Intestinal duodenal biopsies were collected from 402 chil
