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Glucose-dependent insulinotropic polypeptide secretion after oral macronutrient ingestion : The human literature revisited and a systematic study in model experiments in mice

Aims/Introduction: The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is secreted after meal ingestion. This study explored the relative influence of classes of macronutrients on GIP secretion. Materials and Methods: The human literature was revisited by identifying articles from PubMed using key words GIP, macronutrients, carbohydrates, fat, protein, healthy subjects. In mode

Optimizing Exposome-wide Assessments in Cardiometabolic Risk

This thesis is focused on cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D), two concomitant conditions that appear with growing concern. In our work, we aim to improve the identification of individuals at-risk of cardiometabolic disease through the characterization of complex environmental exposures (i.e. diet, physical activity), that temporally vary, and the health effects on card

Is staff consistency important to parents' satisfaction in a longitudinal study of children at risk for type 1 diabetes : the TEDDY study

BACKGROUND: Participants' study satisfaction is important for both compliance with study protocols and retention, but research on parent study satisfaction is rare. This study sought to identify factors associated with parent study satisfaction in The Environmental Determinants of Diabetes in the Young (TEDDY) study, a longitudinal, multinational (US, Finland, Germany, Sweden) study of children at

Long-term results of cytoreduction and HIPEC followed by systemic chemotherapy

Cytoreduction followed by hyperthermic intraperitoneal chemotherapy is a treatment option for peritoneal surface malignancies in The Netherlands. This treatment has been available for more than 10 years. Therefore, long-term results on survival and quality of life can now be studied. With these results, the true long-term benefits of this new management strategy can be determined.

Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria

In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters are involved in maturation of cytosolic iron-sulfur proteins. However, the molecular mechanism for how the ABCB7-type exporters participate in this process remains elusive. Here

PcoB is a defense outer membrane protein that facilitates cellular uptake of copper

Copper (Cu) is one of the most abundant trace metals in all organisms, involved in a plethora of cellular processes. Yet elevated concentrations of the element are harmful, and interestingly prokaryotes are more sensitive for environmental Cu stress than humans. Various transport systems are present to maintain intracellular Cu homeostasis, including the prokaryotic plasmid-encoded multiprotein pc

High-resolution HLA class II sequencing of Swedish multiple sclerosis patients

Multiple sclerosis (MS) is a chronic neurological disease believed to be caused by autoimmune pathogenesis. The aetiology is likely explained by a complex interplay between inherited and environmental factors. Genetic investigations into MS have been conducted for over 50 years, yielding >100 associations to date. Globally, the strongest linkage is with the human leukocyte antigen (HLA) HLA-DRB5*0

HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children

BACKGROUND/OBJECTIVES: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Bi

Obesity-associated Blunted Subcutaneous Adipose Tissue Blood Flow After Meal Improves After Bariatric Surgery

Context: Glucose-dependent insulinotropic peptide (GIP) and meal ingestion increase subcutaneous adipose tissue (SAT) perfusion in healthy individuals. The effects of GIP and a meal on visceral adipose tissue (VAT) perfusion are unclear. Objective: Our aim was to investigate the effects of meal and GIP on VAT and SAT perfusion in obese individuals with type 2 diabetes mellitus (T2DM) before and af

Elucidating causal relationships between energy homeostasis and cardiometabolic outcomes

Energy metabolism dyshomeostasis is associated with multiple health problems. For example, abundant epidemiological data show that obesity and overweight increase the risk of cardiometabolic diseases and early mortality. Type 2 diabetes (T2D), characterized by chronically elevated blood glucose, is also associated with debilitating complications, high healthcare costs and mortality, with cardiovas

Desmoglein-2 is important for islet function and β-cell survival

Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we stu

Regulation of T cells in Atherosclerosis

Atherosclerosis, the underlying pathology of cardiovascular diseases such as myocardial infarction and ischemic stroke, is characterized by chronic inflammation. T cells are present in atherosclerotic plaques and have been implicated in its pathogenesis. This thesis describes studies exploring both the regulation of T cells in atherosclerosis as well as immunomodulatory therapeutics. To study the

Tilt table testing, methodology and practical insights for the clinic

Tilt table testing (TTT) has been used for decades to study short-term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence-based practice syncope guidelines, proper application and interpretation of TTT in the day-to-day care of syncope patients re

Cardiovascular Morbidity and Mortality Related to Non-Alcoholic Fatty Liver Disease : a Systematic Review and Meta-Analysis

BACKGROUND AND AIMS: Whether non-alcoholic fatty liver disease (NAFLD) is a cardiovascular (CV) risk factor is debated. We performed a systematic review and meta-analysis to assess the CV morbidity and mortality related to NAFLD in the general population, and to determine whether CV risk is comparable between lean and non-lean NAFLD phenotypes.METHODS AND RESULTS: We searched multiple databases, i

miRNAs in the beta cell - friends or foes?

Type-2 diabetes (T2D) develops due to insulin resistance and an inability of the pancreatic β-cells to increase secretion of insulin and reduce elevated blood glucose levels. Diminished β-cell function and mass have been implicated in impaired β-cell secretory capacity and several microRNAs (miRNAs) have been reported to be involved in regulating β-cell processes. We believe miRNAs are nodes in im

Other syndromes of orthostatic intolerance : Delayed orthostatic hypotension, postprandial hypotension, postural orthostatic tachycardia syndrome, and reflex syncope

Apart from classical orthostatic hypotension, the gravitational force may strongly contribute to other forms of orthostatic intolerance, delayed and postprandial OH, postural orthostatic tachycardia syndrome (POTS), and reflex syncope. In delayed OH, the significant blood pressure drop occurs first after 3-min period of orthostasis, whereas in postprandial OH, the symptoms appear first approximate

Selectively bred rodent models for studying the etiology of type 2 diabetes : Goto-Kakizaki rats and Oikawa-Nagao mice

Type 2 diabetes (T2D) is a polygenic disease and studies to understand the etiology of the disease have required selectively bred animal models with polygenic background. In this review, we present two models; the Goto-Kakizaki (GK) rat and the Oikawa-Nagao Diabetes-Prone (ON-DP) and Diabetes-Resistant (ON-DR) mouse. The GK rat was developed by continuous selective breeding for glucose tolerance f