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Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities

Resulting from a combination of genetic and environmental factors, type 2 diabetes is highly heterogeneous in manifestation and disease progression, with the only common feature being chronic hyperglycaemia. In spite of vigorous efforts to elucidate the pathogenetic origins and natural course of the disease, there is still a lack of biomarkers and tools for prevention, disease stratification and t

Autoimmune Type 1 Diabetes

In this chapter, the authors summarize the current knowledge of possible trigger(s) of p-cell autoimmunity and factors affecting the progression to the clinical onset in individuals who have developed one or more p-cell autoantibodies. Testing islet autoantibodies at random or in select populations such as schoolchildren should inform about the epidemiology of autoimmune islet disease and what to

Complement factors as biomarkers in ANCA-associated vasculitis in remission

Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare, autoimmune diseases causing inflammation in the vessel wall. Many organs can be affected, and kidney involvement is a common and serious manifestation. Complement activation is important in disease development and has also been detected in patients in remission. The reason for increased complemen

How are socioeconomic status, social support, and health history associated with unhealthy lifestyle behaviours in middle-aged adults? Results of the Swedish CArdioPulmonary bioImage Study (SCAPIS) COHORT

Background: Unhealthy lifestyle behaviours, including unhealthy alcohol consumption, physical inactivity, smoking, and nonadherence to dietary recommendations, are major contributors to non-communicable diseases and mortality. While adopting healthy behaviours can reduce these risks in middle-aged adults, research is limited. Therefore, the aim of this study was to assess the distribution of unhea

Sugar intake and cardiovascular disease risk: With an emphasis on genetic and metabolomic biomarkers of sugar intake

Introduction: Contrary to popular belief, there is limited research on sugar intake as a risk factor for cardiovascular disease. While the links between sugar-sweetened beverage intake and cardiovascular disease risk are well-established, little is known about the associations for overall added or free sugar intake and other dietary sources of added sugar. Objective markers of habitual sugar intak

Prognostic Implications of Orthostatic Hypotension in Elective Coronary Artery Bypass Grafting

BACKGROUND Orthostatic hypotension (OH), defined as a sustained drop in systolic or diastolic blood pressure upon standing, is known to negatively affect survival in the general population. However, its impact on outcomes in patients with advanced coronary artery disease remains unclear. The aim of this study was to assess the prevalence and prognostic value of OH in patients undergoing isolated c

Effect of oral pre-meal administration of betaglucans on glycaemic control and variability in subjects with type 1 diabetes

We conducted a double-blind placebo-controlled crossover pilot study to investigate the effect of oat betaglucans (β-glucan) on glycaemic control and variability in adults with type 1 diabetes (T1D; n = 14). Stomacol® tablets (1.53 g of β-glucan) or placebo (Plac) were administered three times daily before meals for two weeks. Glucose levels were monitored during the second week by continuous gluc

Apolipoprotein A-I attenuates LL-37-induced endothelial cell cytotoxicity

The human cathelicidin peptide LL-37 has antimicrobial and anti-biofilm functions, but LL-37 may also damage the host by triggering inflammation and exerting a cytotoxic effect, thereby reducing host cell viability. Human plasma mitigates LL-37-induced host cell cytotoxicity but the underlying mechanisms are not completely understood. Apolipoprotein A-I (ApoA-I) is a plasma protein endowed with at

Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies

β-cell autoantibodies against insulin (IAA), GAD65 (GADA) and IA-2 (IA-2A) precede onset of childhood type 1 diabetes (T1D). Incidence of the first appearing β-cell autoantibodies peaks at a young age and is patterned by T1D-associated genes, suggesting an early environmental influence. Here, we tested if gestational infections and interactions with child's human leukocyte antigen (HLA) and non-HL

Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2) : a 56-week, double-blind, phase 3a, randomised trial

Background Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. Method

The Human Diabetes Proteome Project (HDPP) : The 2014 update

Diabetes is an increasing worldwide problem leading to major associated health issues and increased health care costs. In 2012, 9.3% of the American population was affected by diabetes, according to the American Diabetes Association, with 1.7 million of new cases since during the year (www.diabetes.org). Proteome initiatives can provide a deeper understanding of the biology of this disease and hel

Nutritional modulation of AMPK-impact upon metabolic-inflammation

Nutritional status provides metabolic substrates to activate AMP-Activated Protein Kinase (AMPK), the energy sensor that regulates metabolism. Recent evidence has demonstrated that AMPK has wider functions with respect to regulating immune cell metabolism and function. One such example is the regulatory role that AMPK has on NLRP3-inlflammasome and IL-1β biology. This in turn can result in subsequ

Interaction of Serum-Derived and Internalized C3 With DNA in Human B Cells-A Potential Involvement in Regulation of Gene Transcription

Beside its classical role as a serum effector system of innate immunity, evidence is accumulating that complement has an intracellular repertoire of components that provides not only immune defense, but also functions to maintain cellular homeostasis. While complement proteins, mainly the central component C3, have been detected in B cells, their exact function and source remain largely unexplored

EndoC-βH5 cells are storable and ready-to-use human pancreatic beta cells with physiological insulin secretion

Objectives: Readily accessible human pancreatic beta cells that are functionally close to primary adult beta cells are a crucial model to better understand human beta cell physiology and develop new treatments for diabetes. We here report the characterization of EndoC-βH5 cells, the latest in the EndoC-βH cell family. Methods: EndoC-βH5 cells were generated by integrative gene transfer of immortal

Enhancing primary care quality improvement through national data collection and validation : the primary care quality initiative in Sweden

Objective: Quality measures in healthcare are crucial for improving outcomes and ensuring patient safety. This study investigated the evolution, implementation, and impact of Primary Care Quality (PCQ). The PCQ aims to facilitate nationwide quality benchmarking, serving as a tool for quality improvement (QI) and research. Design/Settings: A descriptive design outlining the development and operatio

Effects of parental autoimmune diseases on type 1 diabetes in offspring can be partially explained by HLA and non-HLA polymorphisms

Type 1 diabetes (T1D) and other autoimmune diseases (AIDs) often co-occur in families. Leveraging data from 58,284 family trios in Finnish nationwide registers (FinRegistry), we identified that, of 50 parental AIDs examined, 15 were associated with an increased T1D risk in offspring. These identified epidemiological associations were further assessed in 470,000 genotyped Finns from the FinnGen stu

Regenerative performance and immunogenicity of engineered extracellular matrices.

Critical-sized bone defects remain a significant unmet clinical need, with > 500,000 reconstructive procedures performed annually in the United States and Europe and associated costs exceeding US$3 billion. Autologous bone grafting—the current gold standard—suffers from limited harvest volume and donor-site morbidity, whereas allografts show variable integration and carry immunological and infecti