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Genome-wide methylation profiling differentiates benign from aggressive and metastatic pituitary neuroendocrine tumors

Aggressive pituitary neuroendocrine tumors (PitNETs)/adenomas are characterized by progressive growth despite surgery and all standard medical therapies and radiotherapy. A subset will metastasize to the brain and/or distant locations and are termed metastatic PitNETs (pituitary carcinomas). Studies of potential prognostic markers have been limited due to the rarity of these tumors. A few recurren

Biological mechanisms of resilience to tau pathology in Alzheimer’s disease

Background: In Alzheimer’s disease (AD), the associations between tau pathology and brain atrophy and cognitive decline are well established, but imperfect. We investigate whether cerebrospinal fluid (CSF) biomarkers of biological processes (vascular, synaptic, and axonal integrity, neuroinflammation, neurotrophic factors) explain the disconnection between tau pathology and brain atrophy (brain re

Development of a three-dimensional scoring model for the assessment of continuous glucose monitoring data in type 1 diabetes

Introduction Despite the improvements in diabetes management by continuous glucose monitoring (CGM) it is difficult to capture the complexity of CGM data in one metric. We aimed to develop a clinically relevant multidimensional scoring model with the capacity to identify the most alarming CGM episodes and/or patients from a large cohort. Research design and methods Retrospective CGM data from 2017

Patterns and Determinants of Micronutrient Dietary Biomarkers and Their Associations with Dietary Intakes in Young Children

Background: Circulating dietary biomarkers are not direct proxies for intake, as the biomarkers reflect not only food and supplement consumption but also nutrient absorption, metabolism, and tissue distribution. Therefore, along with nutrient intake, several other upstream factors can impact dietary biomarker concentrations, including demographic, medical history, and genetic factors. Objectives:

The 2022 WHO classification of tumors of the pituitary gland : An update on aggressive and metastatic pituitary neuroendocrine tumors

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nerv

Impact of TCF7L2 rs7903146 on clinical presentation and risk of complications in patients with type 2 diabetes

Aims: TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear. Materials and Methods: We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabete

Parent-of-origin effects in the life-course evolution of cardiometabolic traits

AIMS/HYPOTHESIS: Cardiometabolic traits are heritable, and some display parent-of-origin effects, which indicates preferential inheritance from one parent or parental bias. Most studies of these phenomena have focused on adult populations. We aimed to investigate the heritability and parent-of-origin effects on cardiometabolic traits in a birth cohort with serial measurements to determine whether

Structures and strategies for retaining an international pediatric cohort from birth : Lessons from The Environmental Determinants of Diabetes in the Young (TEDDY) study

Background: Retention of study participants in observational studies is essential to maintaining the representativeness of the population, minimizing selection bias, and assuring sufficient statistical power. The aim of this report is to describe the structures and strategies used to retain participants in The Environmental Determinants of Diabetes in the Young (TEDDY) Study, an observational stud

The Physical Activity Health Paradox in Type 2 Diabetes

Introduction: The physical activity health paradox refers to the contrasting associations of leisure-time physical activity and occupational physical activity with cardiovascular disease, but whether this applies to Type 2 diabetes risk is unknown. This study aimed to investigate the physical activity health paradox and age-specific Type 2 diabetes. Methods: Working adults (N=5,866) in Denmark age

Hybrid speciation driven by multilocus introgression of ecological traits

Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific trait

Aspects of Sex Differences in Type 1 Diabetes

Abstract:Background Type 1 diabetes (T1D) is one of the most common childhood autoimmune diseases, with rising incidence worldwide with a male predominance. The etiology behind the disease is mostly unknown and it is essential to understand the factors that impact its development to prevent the disease and personalize the treatment. This thesis aims to examine sex-specific differences in T1D, expl

Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy

Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identifi

Atrial Fibrillation and Clonal Hematopoiesis in TET2 and ASXL1

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling. Objective: To determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes. Design, Setting, and Participants: This was a population-based, prospective cohort

Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes

Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes1. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR–GLP-1R co-agonist tirzepatide2 and AMG-133 (ref

CRP, C-Peptide, and Risk of First-Time Cardiovascular Events and Mortality in Early Type 2 Diabetes : A Danish Cohort Study

We investigated the relationship between hs-CRP, a marker of low-grade inflam-mation, alone or in combination with C-peptide, a marker of hyperinsulinemia/ insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-pep

Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility

Background: Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance. Methods: In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated

Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes

Background/Aim: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody-positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Curre

Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes

BACKGROUND: Neutrophils and their inflammatory mediators are key pathogenic components in multiple autoimmune diseases, while their role in human type 1 diabetes (T1D), a disease that progresses sequentially through identifiable stages prior to the clinical onset, is not well understood. We previously reported that the number of circulating neutrophils is reduced in patients with T1D and in presym