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Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this stud
Type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, is a chronic disease characterized by insulin deficiency due to pancreatic β-cell loss and leads to hyperglycaemia. Although the age of symptomatic onset is usually during childhood or adolescence, symptoms can sometimes develop much later. Although the aetiology of T1DM is not completely understood, the pathogenesis of the diseas
Type 2 diabetes (T2D) is a metabolic disease characterized by insufficient insulin secretion and insulin resistance. Disturbed beta-cell function is the final culprit that leads to the development of T2D. In addition, impaired incretin effect is likely a part of the pathogenesis of T2D. The aim of this thesis was to study the role of CART in beta-cells and incretin producing L- and K-cells.Endogen
Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating va
Gestational diabetes mellitus(GDM) defines an unhealthy state of hyperglycaemia that develops in response to an otherwise normal physiological adaptive insulin resistance state during pregnancy. However, the exact plasma glucose levels differentiating the unhealthy GDM state from a normal pregnancy is unknown, and relies upon arbitrary cut off criteria based on associations with adverse health out
This study delineates the permissible scope for compulsory mental health interventions under the Convention on the Rights of Persons with Disabilities (CRPD). It was initially triggered by two competing positions within the current debate over the future of coercive psychiatry; a practice that is still omnipresent among states worldwide. According to one position, defended by the CRPD Committee amThis study delineates the permissible scope for compulsory mental health interventions under the Convention on the Rights of Persons with Disabilities (CRPD). It was initially triggered by two competing positions within the current debate over the future of coercive psychiatry; a practice that is still omnipresent among states worldwide. According to one position, defended by the CRPD Committee am
BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66
Purpose Autoantibodies against osteoprotegerin (OPG) have been associated with osteoporosis. The aim was to develop an immunoassay for OPG autoantibodies and test their diagnostic usefulness of identifying women general population with low bone mineral density. Methods Included were 698 women at mean age 55.1 years (range 50.4–60.6) randomly selected from the general population. Measurement of wri
OBJECTIVE: Treatments have failed to delay or stop the autoimmune process, preceding onset of type 1 diabetes. We investigated if autoantigen-specific treatment with alum-formulated glutamate decarboxylase (GAD-Alum) was safe and affected progression to type 1 diabetes in children with islet autoimmunity.METHODS: In an investigator-initiated, double-blind, placebo-controlled clinical trial, non-di
Background: There is a need for increased understanding of the pre-diabetic period in individuals with high risk of type 1 diabetes from the general population. Methods: High-risk children (n = 21) positive for multiple islet autoantibodies were identified by autoantibody screening within the All Babies in Southeast Sweden study. The children and their parents were enrolled in a 2-year prospective
Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impai
Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In child
Ca2+-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the TRP family members in β-cells from diabetic donors.
OBJECTIVE Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow'smilk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort. RESEARCH DESIGN AND METHODS The Environmental De
BACKGROUND - Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. APPROACH - An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A newsystemwas developed to grade the overall quality of the evidenc
AIM: The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1-h glucose value, in a high-risk Indian popula
This paper seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to T1D risk among autoantibody positive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high
AIMS: The onset of clinical type 1 diabetes (T1D) is preceded by the occurrence of disease-specific autoantibodies. The level of autoantibody titers is known to be associated with progression time from the first emergence of autoantibodies to the onset of clinical symptoms, but detailed analyses of this complex relationship are lacking. We aimed to fill this gap by applying advanced statistical mo
