Increased incidence of pediatric type 1 diabetes during the pandemic in Biscay, Spain.

Objective: To update the incidence rate (IR) and trends of type 1 diabetes mellitus (T1DM) in children aged 0-14 years from 2003 to 2022, in Biscay, Spain.

Subjects And Method: We used the capture-recapture method: primary cases were prospectively extracted from the hospital registry and a secondary independent data source was obtained from diabetes associations and a public health database. The IRs standardized by age and sex were calculated using the direct method, assuming an equal distribution in each age/sex group.

Risk for progression to type 1 diabetes in first-degree relatives under 50 years of age.

Introduction: The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors.

Cytomegalovirus durably primes neutrophil oxidative burst.

Cytomegalovirus (CMV) is a ubiquitous herpes virus that infects most humans, thereafter persisting lifelong in tissues of the host. It is a known pathogen in immunosuppressed patients, but its impact on immunocompetent hosts remains less understood. Recent data have shown that CMV leaves a significant and long-lasting imprint in host immunity that may confer some protection against subsequent bacterial infection.

Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations.

NR5A1/SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or may be found in healthy carriers. The NR5A1/SF-1 c.437G>C/p.

Autoimmune Diabetes From Childhood to Adulthood: The Role of Pancreatic Autoantibodies and HLA-DRB1 Genotype.

Context: Autoimmune diabetes can develop at any age, but unlike early-onset diabetes, adult onset is less well documented. We aimed to compare, over a wide age range, the most reliable predictive biomarkers for this pathology: pancreatic-autoantibodies and HLA-DRB1 genotype.

Methods: A retrospective study of 802 patients with diabetes (aged 11 months to 66 years) was conducted.

Association between hepcidin and type 2 diabetes markers in indigenous Argentinean children living at high altitude.

Background: Hepcidin is a protein that regulates the metabolism of iron. In addition, a high iron load can cause insulin resistance and subsequent diabetes.

Objective: To investigate the association between hepcidin levels and glucose, insulin, lipids, HOMA-IR, and inflammatory markers, C reactive protein (CRP), ferritin, Lp (a), and leucocytes, in indigenous school children living at 4000 m above sea level.

Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2.

Aims: Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM).

An Integrated Pharmacological, Structural, and Genetic Analysis of Extracellular Versus Intracellular ROS Production in Neutrophils.

The neutrophil NADPH oxidase produces both intracellular and extracellular reactive oxygen species (ROS). Although oxidase activity is essential for microbial killing, and ROS can act as signaling molecules in the inflammatory process, excessive extracellular ROS directly contributes to inflammatory tissue damage, as well as to cancer progression and immune dysregulation in the tumor microenvironment. How specific signaling pathways contribute to ROS localization is unclear.

Plasma and wound fluids from trauma patients suppress neutrophil extracellular respiratory burst.

Background: Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Polymorphonuclear neutrophils (PMNs) migrate toward bacteria using chemotaxis, trap them in extracellular neutrophil extracellular traps, and kill them using respiratory burst (RB).

Clinical and genetic characteristics in patients under 30 years with sporadic pituitary adenomas.

Objective: Pituitary adenomas (PA) are rare in young patients, and additional studies are needed to fully understand their pathogenesis in this population. We describe the clinical and genetic characteristics of apparently sporadic PA in a cohort of young patients.

Design: Clinical and molecular analysis of 235 patients (age ≤ 30 years) with PA.

Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial.

Objective: To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup.

Research Design And Methods: In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.

Potential of Erythrocyte Membrane Lipid Profile as a Novel Inflammatory Biomarker to Distinguish Metabolically Healthy Obesity in Children.

Metabolically healthy obesity (MHO) has been described as BMI ≥ 30 kg/m, without metabolic disorders traditionally associated with obesity. Beyond this definition, a standardized criterion, for adults and children, has not been established yet to explain the absence of those metabolic disorders. In this context, biomarkers of inflammation have been proposed as suitable candidates to describe MHO.

Role of Mitochondria-Derived Danger Signals Released After Injury in Systemic Inflammation and Sepsis.

Sepsis is a major public health concern, with high mortality and morbidity, especially among patients undergoing trauma. It is characterized by a systemic inflammatory response syndrome (SIRS) occurring in response to infection. Although classically associated with pathogens, many patients with SIRS do not have infection.

Molecular Differences Based on Erythrocyte Fatty Acid Profile to Personalize Dietary Strategies between Adults and Children with Obesity.

As the obesity epidemic continues to grow inexorably worldwide, the need to develop effective strategies to prevent and control obesity seems crucial. The use of molecular tools can be useful to characterize different obesity phenotypes to provide more precise nutritional recommendations. This study aimed to determine the fatty acid (FA) profile of red blood cell (RBC) membranes, together with the evaluation of their dietary intake and biochemical parameters, of children and adults with obesity.

Fatty Acid Profile of Mature Red Blood Cell Membranes and Dietary Intake as a New Approach to Characterize Children with Overweight and Obesity.

Obesity is a chronic metabolic disease of high complexity and of multifactorial origin. Understanding the effects of nutrition on childhood obesity metabolism remains a challenge. The aim of this study was to determine the fatty acid (FA) profile of red blood cell (RBC) membranes as a comprehensive biomarker of children's obesity metabolism, together with the evaluation of their dietary intake.

Direct Airway Instillation of Neutrophils Overcomes Chemotactic Deficits Induced by Injury.

Background: Trauma induces neutrophil migration toward injury sites, both initiating wound healing and protecting against local bacterial infection. We have previously shown that mitochondrial formyl peptides (mtFPs) released by injured tissues act as chemoattractants by ligating neutrophil (PMN) formyl peptide receptor 1 (FPR1). But this process can also internalize multiple neutrophil chemoattractant receptors and thus might limit neutrophil migration to the lung in response to bacteria.

Forty-One Individuals With Mutations in the AVP-NPII Gene Associated With Familial Neurohypophyseal Diabetes Insipidus.

Context: Familial neurohypophyseal diabetes insipidus is a rare disease produced by a deficiency in the secretion of antidiuretic hormone and is caused by mutations in the arginine vasopressin gene.

Objective: Clinical, biochemical, and genetic characterization of a group of patients clinically diagnosed with familial neurohypophyseal diabetes insipidus, 1 of the largest cohorts of patients with protein neurophysin II (AVP-NPII) gene alterations studied so far.

Design: The AVP-NPII gene was screened for mutations by PCR followed by direct Sanger sequencing in 15 different unrelated families from Spain.

Formyl Peptide Receptor-1 Blockade Prevents Receptor Regulation by Mitochondrial Danger-Associated Molecular Patterns and Preserves Neutrophil Function After Trauma.

Objectives: Trauma predisposes to systemic sterile inflammation (systemic inflammatory response syndrome) as well as infection, but the mechanisms linking injury to infection are poorly understood. Mitochondrial debris contains formyl peptides. These bind formyl peptide receptor-1, trafficking neutrophils to wounds, initiating systemic inflammatory response syndrome, and wound healing.

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

Objective: Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease.

Thyroid hormone resistance from newborns to adults: a Spanish experience.

Objective: Thyroid hormone resistance (RTH β) is a rare genetic disorder characterized by an altered response of target tissue to the action of thyroid hormone. Few studies on RTH β have been carried out in southern European populations. We aimed to describe the clinical and genetic characteristics at the time of diagnosis in a Spanish cohort of patients with genetically confirmed RTH β, with ages ranging from newborns to adults.

For Debate: Paediatric T1DM: DKA is Still a Problem.

Unlabelled: Although the treatment of pediatric patients with T1DM has improved ketoacidosis (DKA) remains a frequent problem.

Objective: To estimate temporal changes in the prevalence of DKA at diagnosis of T1DM and to explore the factors associated with its occurrence.

Methods: Paediatric patients diagnosed at Cruces University Hospital (Spain) since 1997 were included.