PET imaging of GABA receptors in pancreatic islets by [C]flumazenil.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABARs) in pancreatic islets and the fact that GABAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [C]flumazenil ([C]FMZ) could serve as a marker of the endocrine mass of the pancreas.

Development of a three-dimensional scoring model for the assessment of continuous glucose monitoring data in type 1 diabetes.

Introduction: Despite the improvements in diabetes management by continuous glucose monitoring (CGM) it is difficult to capture the complexity of CGM data in one metric. We aimed to develop a clinically relevant multidimensional scoring model with the capacity to identify the most alarming CGM episodes and/or patients from a large cohort.

Research Design And Methods: Retrospective CGM data from 2017 to 2020 available in electronic medical records were collected from n=613 individuals with type 1 diabetes (total 82 114 days).

Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes.

Introduction: The rate of progression to complete insulin deficiency varies greatly in type 1 diabetes. This constitutes a challenge, especially when randomizing patients in intervention trials aiming to preserve beta cell function. This study aimed to identify biomarkers predictive of either a rapid or slow disease progression in children with new-onset type 1 diabetes.

Non-invasive imaging of sympathetic innervation of the pancreas in individuals with type 2 diabetes.

Aims/hypothesis: Compromised pancreatic sympathetic innervation has been suggested as a factor involved in both immune-mediated beta cell destruction and endocrine dysregulation of pancreatic islets. To further explore these intriguing findings, new techniques for in vivo assessment of pancreatic innervation are required. This is a retrospective study that aimed to investigate whether the noradrenaline (norepinephrine) analogue C-hydroxy ephedrine (C-HED) could be used for quantitative positron emission tomography (PET) imaging of the sympathetic innervation of the human pancreas.

Real-life data of hypoglycemic events in children and adolescents with type 1 diabetes.

Introduction: Hypoglycemia composes an always present risk in the treatment of type 1 diabetes (T1D) and can be a fatal complication. Many studies on hypoglycemic events are based on self-reported data or focused on the aggregated time below range. We have processed continuous glucose monitoring (CGM) data in children and adolescents with T1D in order to examine all occurring hypoglycemic events.

Umbilical cord-derived mesenchymal stromal cells preserve endogenous insulin production in type 1 diabetes: a Phase I/II randomised double-blind placebo-controlled trial.

Aim/hypothesis: This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes.

Methods: A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.

Classification of Hypoglycemic Events in Type 1 Diabetes Using Machine Learning Algorithms.

Introduction: To improve the utilization of continuous- and flash glucose monitoring (CGM/FGM) data we have tested the hypothesis that a machine learning (ML) model can be trained to identify the most likely root causes for hypoglycemic events.

Methods: CGM/FGM data were collected from 449 patients with type 1 diabetes. Of the 42,120 identified hypoglycemic events, 5041 were randomly selected for classification by two clinicians.

Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis.

Introduction: The progression to insulin deficiency in type 1 diabetes is heterogenous. This study aimed to identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course.

Research Design And Methods: Stimulated C-peptide was assessed by mixed meal tolerance test in 50 children (<18 years) during 2004-2017, at regular intervals for 6 years from type 1 diabetes diagnosis.

Pregnancy induces pancreatic insulin secretion in women with long-standing type 1 diabetes.

Introduction: Pregnancy entails both pancreatic adaptations with increasing β-cell mass and immunological alterations in healthy women. In this study, we have examined the effects of pregnancy on β-cell function and immunological processes in long-standing type 1 diabetes (L-T1D).

Research Design And Methods: Fasting and stimulated C-peptide were measured after an oral glucose tolerance test in pregnant women with L-T1D (n=17) during the first trimester, third trimester, and 5-8 weeks post partum.

Security and Safety Concerns in Air Taxis: A Systematic Literature Review.

Different from traditional transport systems, such as cars or trains, which are limited by land transit space, flying cars (such as UAS, drones, and air taxis) do not occupy space with traffic. They have a degree of freedom in space and time, smaller displacement, and consequently, less stress for their users. Large companies and researchers around the world are working with different architectures, algorithms, and techniques to test air taxi transport to serve a significant proportion of people safely and autonomously.

Irisin-A Pancreatic Islet Hormone.

Irisin is a myokine involved in glucose homeostasis. It is primarily expressed in skeletal muscle, but also in the pancreas. This study aimed to elucidate its presence and role in the islets of Langerhans-i.

Endogenous Levels of Gamma Amino-Butyric Acid Are Correlated to Glutamic-Acid Decarboxylase Antibody Levels in Type 1 Diabetes.

Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system (CNS) and outside of the CNS, found in the highest concentrations in immune cells and pancreatic beta-cells. GABA is gaining increasing interest in diabetes research due to its immune-modulatory and beta-cell stimulatory effects and is a highly interesting drug candidate for the treatment of type 1 diabetes (T1D). GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), one of the targets for autoantibodies linked to T1D.

Interleukin-35 Prevents Development of Autoimmune Diabetes Possibly by Maintaining the Phenotype of Regulatory B Cells.

The anti-inflammatory role of regulatory B cells (Breg cells) has been associated with IL-35 based on studies of experimental autoimmune uveitis and encephalitis. The role of Breg cells and IL-35 Breg cells for type 1 diabetes (T1D) remains to be investigated. We studied PBMCs from T1D subjects and healthy controls (HC) and found lowered proportions of Breg cells and IL-35 Breg cells in T1D.

GABA induces a hormonal counter-regulatory response in subjects with long-standing type 1 diabetes.

Introduction: Experimentally, gamma-aminobutyric acid (GABA) has been found to exert immune-modulatory effects and induce beta-cell regeneration, which make it a highly interesting substance candidate for the treatment of type 1 diabetes (T1D). In many countries, including those in the European Union, GABA is considered a pharmaceutical drug. We have therefore conducted a safety and dose escalation trial with the first controlled-release formulation of GABA, Remygen (Diamyd Medical).

Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial.

The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.

Changes in Circulating Cytokines and Adipokines After RYGB in Patients with and without Type 2 Diabetes.

Objective: This study aimed to compare cytokine and adipokine levels in patients with obesity with and without type 2 diabetes (T2D) at baseline and 6 months after Roux-en-Y gastric bypass (RYGB) with healthy controls.

Methods: A total of 34 patients (21 with T2D) with BMI of 30 to 45 kg/m were compared with 25 healthy controls without obesity. Cytokines, adipokines, and peptides of relevance for inflammation and metabolism were analyzed in plasma.

Longitudinal Assessment of C-5-Hydroxytryptophan Uptake in Pancreas After Debut of Type 1 Diabetes.

The longitudinal alterations of the pancreatic β-cell and islet mass in the progression of type 1 diabetes (T1D) are still poorly understood. The objective of this study was to repeatedly assess the endocrine volume and the morphology of the pancreas for up to 24 months after T1D diagnosis ( = 16), by C-5-hydroxytryptophan (C-5-HTP) positron emission tomography (PET) and MRI. Study participants were examined four times by PET/MRI: at recruitment and then after 6, 12, and 24 months.

CART decreases islet blood flow, but has no effect on total pancreatic blood flow and glucose tolerance in anesthetized rats.

Cocaine- and amphetamine-regulated transcript (CART) is a neurotransmitter and hormone, involved in the regulation of e.g. food intake, body weight, reward and addiction, and stress response.

Increased Plasma Levels of the Co-stimulatory Proteins CDCP1 and SLAMF1 in Patients With Autoimmune Endocrine Diseases.

Despite that autoimmune diseases share similar immunogenetic mechanisms, studies comparing the protein composition in peripheral blood from patients with autoimmune endocrine diseases are limited. In this study, we applied proximity extension assay to measure proteins related to signaling and interactions within the immune system in peripheral blood from patients with new-onset (N-T1D) and long-standing (L-T1D) type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease (GD), and autoimmune Addison's disease in addition to healthy controls (HC). Proteins in plasma and supernatants from cultured PBMC were measured by using a 92-plex Olink® INFLAMMATION panel.

Unsurpassed Intrahepatic Islet Engraftment - the Quest for New Sites for Beta Cell Replacement.

The liver is currently the site of choice for clinical islet transplantation, even though many alternative implantation sites have lately been proposed as more ideal for graft survival. The suggested sites, for example intramuscular space, omentum, bone marrow, and spleen, are sometimes difficult to compare due to differences in animal model, islet isolation procedure, and islet quality. In addition, the variation in transplanted islet mass is vast.

Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack.

Differences in pancreatic islet susceptibility during type 1 diabetes development may be explained by interislet variations. This study aimed to investigate if heterogeneities in vascular support and metabolic activity in rat and human islets may explain why some islets are attacked earlier than other islets. In rats, highly blood perfused islets were identified by injection of microspheres into the ascending aorta, whereas a combination of anterograde and retrograde injections of microspheres into pancreas was used to determine the islet vascular drainage system.

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets.

Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20CD27CD38HLA-DR plasmablasts, CD86CD14CD16 non-classical monocytes and two subsets of CD56HLA-DRIFN-γ NK cells were increased in patients with HT.

Better HbA1c during the first years after diagnosis of type 1 diabetes is associated with residual C peptide 10 years later.

Objective: To identify the factors associated with residual C peptide production at least 10 years after diagnosis in children and adolescents with type 1 diabetes.

Research Design And Methods: 73 children and adolescents (<25 years), born in 1988-2005, diagnosed with type 1 diabetes were included during the 4-year study period (2013-2016). At least 10 years after diagnosis, we measured any remaining C peptide concentration using an ultrasensitive C peptide ELISA (≥1.

[Amyloid from insulin treatment: a pitfall for the pathologist and the diabetologist].

Biopsies from six diabetic patients with subcutaneous amyloid deposits formed by injected insulin have been sent to our laboratory during the last year. In all but one of the six patients a subcutaneous adipose tissue biopsy was taken due to suspicion of systemic amyloidosis. Four of these patients had renal insufficiency, with monoclonal gammopathy of undetermined significance (MGUS) in three while the fifth had heredity for transthyretin amyloidosis.

Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery.

Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).

Research Design And Methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.