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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans

OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identif

Variation in Glucose Homeostasis Traits Associated With P2RX7 Polymorphisms in Mice and Humans

Context: Extracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function. Objective: We hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction. Design: In humans, we mined genome-

Plasma Vitamins B2, B6, and B12, and Related Genetic Variants as Predictors of Colorectal Cancer Risk

Background: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. Methods: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, includ

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with

Impact of the tcf7l2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia

Introduction: In healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM). Material and method

Mortality in first- and second-generation immigrants to Sweden diagnosed with type 2 diabetes : a 10 year nationwide cohort study

Aims/hypothesis: Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes. Methods: People living in Sweden diagnosed with new-onset pharmacologically treated type

Circulating testican-2 is a podocyte-derived marker of kidney health

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that c

Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation–can blood be used as a surrogate for bone?

Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene–environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecula

Associations of breastfeeding with childhood autoimmunity, allergies, and overweight : The Environmental Determinants of Diabetes in the Young (TEDDY) study

BACKGROUND: Breastfeeding has beneficial effects on numerous health outcomes.OBJECTIVES: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort.METHODS: Infants with genetic susceptibility for type 1 diabetes (n = 8676) were followed for the development of autoantibodies to

PEPRF : Identification of Essential Proteins by Integrating Topological Features of PPI Network and Sequence-based Features via Random Forest

Background: Essential proteins play an important role in the process of life, which can be identified by experimental methods and computational approaches. Experimental approaches to identify essential proteins are of high accuracy but with the limitation of time and resource-consuming. Objective: Herein, we present a computational model (PEPRF) to identify essential proteins based on machine lear

Perceptions, experiences and barriers to lifestyle modifications in first-generation Middle Eastern immigrants to Sweden : A qualitative study

Objective The prevalence of type 2 diabetes (T2D) among Iraqi immigrants to Sweden is high and partly related to sedentary physical activity and calorie dense food. The aim of the present study was to explore perceptions, experiences and barriers concerning lifestyle modifications (LSM) in Iraqi immigrants to Sweden at risk for T2D. Design A qualitative thematic analysis was conducted on data coll

Dödligheten förändras hos immigranter med diabetes

Non-western immigrants have a higher prevalence of type 2 diabetes and earlier onset than non-immigrant Swedes. In this 10-year follow-up including all people in Sweden diagnosed with type 2 diabetes from 2006 onwards (i.e. prescribed glucose lowering medication for type 2 diabetes), the total and cause-specific mortality of first-generation immigrants with type 2 diabetes is lower than in non-imm

A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen

Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglut

ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents with Celiac Disease

There is a need for consensus on the recommendations for follow-up of children and adolescents with celiac disease. Objectives: To gather the current evidence and to offer recommendations for follow-up and management. Methods: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essen

Intestinal gluconeogenesis is downregulated in pediatric patients with celiac disease

Background: Untreated celiac disease (CD) patients have increased levels of blood glutamine and a lower duodenal expression of glutaminase (GLS). Intestinal gluconeogenesis (IGN) is a process through which glutamine is turned into glucose in the small intestine, for which GLS is crucial. Animal studies suggest impaired IGN may have long-term effects on metabolic control and be associated with the

Incidence of celiac disease autoimmunity and associations with maternal tuberculosis and pediatric Helicobacter pylori infections in 4-year-old Ethiopian children followed up in an HLA genotyped birth cohort

Background: The prevalence of celiac disease in the general population is mainly unknown in most of sub-Saharan African countries. The aim of this study was to determine the incidence of celiac disease autoimmunity (CDA) and its associations with latent Mycobacterium tuberculosis (LMTB) and Helicobacter pylori (HP) infections in Ethiopian children aged 4 years in an HLA genotyped cohort study. Met