Effect of fenofibrate on residual beta cell function in adults and adolescents with newly diagnosed type 1 diabetes: a randomised clinical trial.

Aims/hypothesis: Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, shows some promise in alleviating beta cell stress and preserving beta cell function in preclinical studies of type 1 diabetes. The aim of this phase 2, placebo-controlled, double-blinded, randomised clinical trial was to investigate the efficacy and safety of fenofibrate in adults and adolescents with newly diagnosed type 1 diabetes.

Methods: We enrolled 58 individuals (aged 16 to 40 years old) with newly diagnosed type 1 diabetes and randomised them to daily oral treatment with fenofibrate 160 mg or placebo for 52 weeks (in a block design with a block size of 4, assigned in a 1:1 ratio).

Probiotic treatment with viable α-galactosylceramide-producing Bacteroides fragilis reduces diabetes incidence in female nonobese diabetic mice.

Background: We aimed to investigate whether alpha-galactosylceramide (α-GalCer)-producing Bacteroides fragilis could induce natural killer T (NKT) cells in nonobese diabetic (NOD) mice and reduce their diabetes incidence.

Methods: Five-week-old female NOD mice were treated orally with B. fragilis, and islet pathology and diabetes onset were monitored.

Beta-cell activity and development of Type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease, resulting in diminished islet integrity and destruction of the insulin-secreting beta cells. In this review, we investigate the intrinsic relationship between the development of T1D and the activity of the beta cells. The idea was initially hypothesized in 1982 that an increased beta-cell activity would enhance the surface antigen expression and thereby attract the immune system.

Influence of sphingolipid enzymes on blood glucose levels, development of diabetes, and involvement of pericytes.

Aims: Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis.

Failure to replicate the diabetes alleviating effect of a maternal gluten-free diet in non-obese diabetic mice.

Type 1 diabetes (T1D) is an autoimmune disease with an unexplained rising incidence for which environmental factors like gluten may play a role. Previously, we showed that a gluten-free (GF) diet provided strictly in utero reduces the autoimmune diabetes incidence in Non-Obese Diabetic (NOD) mice compared to a gluten-containing standard (STD) diet. The current study was initiated to elucidate possible mechanisms behind the diabetes-alleviating effect of the same diet intervention.

Hibernation and plasma lipids in free-ranging brown bears-implications for diabetes.

Brown bears (Ursus arctos) prepare for winter by overeating and increasing adipose stores, before hibernating for up to six months without eating, drinking, and with minimal movement. In spring, the bears exit the den without any damage to organs or physiology. Recent clinical research has shown that specific lipids and lipid profiles are of special interest for diseases such as diabetes type 1 and 2.

Type 1 diabetes could begin with alterations in innate anti-viral immunity, which are already at this stage associated with HLA risk haplotypes.

Aims: To investigate if HLA risk haplotypes and HbA1c levels are associated with the expression levels of innate anti-viral immune pathway genes in type 1 diabetes.

Materials And Methods: We investigated RNA expression levels of innate anti-viral immune pathway genes in laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection study and the network of Pancreatic Organ Donors in relation to HLA risk haplotypes (non-predisposed and predisposed) and HbA1c levels (normal, elevated, and high).

Results: The expression of innate anti-viral immune genes (TLR7, OAS1, OAS3 etc.

A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice.

The incidence of the autoimmune disease type 1 diabetes is increasing, likely caused by environmental factors. A gluten-free diet has previously been shown to ameliorate autoimmune diabetes in non-obese diabetic (NOD) mice and humans. Although the exact mechanisms are not understood, interventions influencing the intestinal microbiota early in life affect the risk of type 1 diabetes.

Sulfatide inhibits fibroblast growth, activation and oxidative stress induced by ectopic insulin.

Aim: To study the effect of sulfatide on gene expression and proliferation of human primary fibroblasts induced by insulin, insulin-like growth factor-1 and human growth hormone.

Materials And Methods: Human primary fibroblasts were exposed to 1, 3 and 30 μM of sulfatide or its precursor galactosylceramide (GalCer). Proliferation was determined by H-thymidine incorporation and gene expression via microarray analysis.

The C24:0 Sulfatide Isoform as an Important Molecule in Type 1 Diabetes.

Particular molecules play pivotal roles in the pathogenesis of many autoimmune diseases. We suggest that the C24:0 sulfatide isoform may influence the development of type 1 diabetes (T1D). C24:0 sulfatide is a sphingolipid with a long carbon-atom chain.

Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism.

Background: At diagnosis of Type 1 Diabetes (T1D), 30% of the beta cells are dormant, i.e. alive, but inactive.

PDE12 in type 1 diabetes.

Type 1 diabetes (T1D) incidence is increased after COVID-19 infection in children under 18 years of age. Interferon-α-activated oligoadenylate synthetase and downstream RNAseL activation degrade pathogen RNA, but can also damage host RNA when RNAseL activity is poorly regulated. One such regulator is PDE12 which degrades 2'-5' oligoadenylate units, thereby decreasing RNAseL activity.

The etiology and pathogenesis of type 1 diabetes - A personal, non-systematic review of possible causes, and interventions.

In this review after a lifelong research career, my personal opinion on the development of type 1 diabetes (T1D) from its very start to clinical manifestation will be described. T1D is a disease of an increased intestinal permeability and a reduced pancreas volume. I am convinced that virus might be the initiator and that this virus could persist on strategically significant locations.

Effect of gluten-free diet and antibiotics on murine gut microbiota and immune response to tetanus vaccination.

The purpose of this study was to compare the effect of a gluten-free diet and/or antibiotics on tetanus vaccine induced immunoglobulin G titers and immune cell levels in BALB/c mice. The gluten-free diet was associated with a reduced anti-tetanus IgG response, and it increased the relative abundance of the anti-inflammatory Bifidobacterium significantly in some of the mice. Antibiotics also led to gut microbiota changes and lower initial vaccine titer.

Gluten-free diet reduces autoimmune diabetes mellitus in mice across multiple generations in a microbiota-independent manner.

Experimental and clinical data suggest that a gluten-free diet attenuates the development of type 1 diabetes. A gluten-free diet changes the gut microbiota composition, and such microbial changes are expected to reduce the autoimmune responses. However, in experiments with laboratory mice, a gluten-free diet changes the gut microbiota differently under varying experimental settings, questioning the specific role of the gut microbes.

Intestinal permeability in type 1 diabetes: An updated comprehensive overview.

The etiopathogenesis of the autoimmune disease type 1 diabetes (T1D) is still largely unknown, however, both genetic and environmental factors contribute to the development of the disease. A major contact surface for environmental factors is the gastrointestinal (GI) tract, where barrier defects in T1D likely cause diabetogenic antigens to enter the body tissues, contributing to beta-cell autoimmunity. Human and animal research imply that increased intestinal permeability is an important disease determinant, although the underlying methodologies, interpretations and conclusions are diverse.

Genetic predisposition in the 2'-5'A pathway in the development of type 1 diabetes: potential contribution to dysregulation of innate antiviral immunity.

Aims/hypothesis: The incidence of type 1 diabetes is increasing more rapidly than can be explained by genetic drift. Viruses may play an important role in the disease, as they seem to activate the 2'-5'-linked oligoadenylate (2'-5'A) pathway of the innate antiviral immune system. Our aim was to investigate this possibility.

Gluten-free diet modulates inflammation in salivary glands and pancreatic islets.

Objectives: A lifelong gluten-free (GF) diet ameliorates autoimmune diabetes in non-obese diabetic (NOD) mice and most likely in humans. Besides diabetes, NOD mice develop focal sialadenitis, as seen in Sjögren's syndrome (SS). In humans, type 1 diabetes (T1D) is also linked to SS.

Antibiotic treatment during early childhood and risk of type 1 diabetes in children: A national birth cohort study.

Objective/background: Antibiotics are widely used during childhood infections and influence the composition of the microbiota, which is established during the first years of life. Evidence from animal models of type 1 diabetes shows that antibiotics might accelerate disease progression, and altered intestinal microbiota has been reported in association with type 1 diabetes in humans. We aimed to test the hypothesis that early exposure to antibiotics (0-24 months of age) was associated with an increased risk of childhood type 1 diabetes development.