Targeted serum proteomics of longitudinal samples from newly diagnosed youth with type 1 diabetes distinguishes markers of disease and C-peptide trajectory
Conclusions/interpretationThe association of several targeted proteins with fasting C-peptide/glucose levels in the first year after diagnosis suggests their connection with the underlying changes accompanying alterations in beta cell function in type 1 diabetes. Moreover, the direction of change in GPX3 during the first year was indicative of subsequent fasting C-peptide/glucose levels, and supports further investigation of this and other serum protein measurements in future studies of beta cell function in type 1 diabetes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes
Conclusions/interpretation68Ga-DOTATATE uptake across the cardio –haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore,68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes.Trial registrationClinicalTrials.gov NCT05730634Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells
Conclusions/interpretationTaken together, these data highlight an important link between ER Ca2+ homeostasis and proinsulin processing in beta cells. Our findings suggest a model whereby chronic ER Ca2+ depletion due to SERCA2 deficiency impairs the spatial regulation of prohormone trafficking, processing and maturation within the secretory pathway.Data availabilityRNA-seq data have been deposited in the Gene Expression Omnibus (GEO; accession no.: GSE207498).Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes
Conclusions/interpretationOur findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing
Conclusions/interpretationNon-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
Islet autoimmunity in human type 1 diabetes: initiation and progression from the perspective of the beta cell
AbstractType 1 diabetes results from the poorly understood process of islet autoimmunity, which ultimately leads to the loss of functional pancreatic beta cells. Mounting evidence supports the notion that the activation and evolution of islet autoimmunity in genetically susceptible people is contingent upon early life exposures affecting the islets, especially beta cells. Here, we review some of the recent advances and studies that highlight the roles of these changes as well as antigen presentation and stress response pathways in beta cells in the onset and propagation of the autoimmune process in type 1 diabetes. Future ...
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
A first-in-human, open-label Phase 1b and a randomised, double-blind Phase 2a clinical trial in recent-onset type 1 diabetes with AG019 as monotherapy and in combination with teplizumab
Conclusions/interpretationOral delivery of AG019 was well tolerated and safe as monotherapy and in combination with teplizumab. AG019 was not shown to interfere with the safety profile of teplizumab and may have additional biological effects, including changes in preproinsulin-specific T cells. These preliminary data support continuing studies with this agent alone and in combination with teplizumab or other systemic immunotherapies in type 1 diabetes.Trial registrationClinicalTrials.gov NCT03751007, EudraCT 2017-002871-24FundingThis study was funded by Precigen ActoBioGraphical Abstract (Source: Diabetologia)
Source: Diabetologia - October 2, 2023 Category: Endocrinology Source Type: research
IFN ɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity
Conclusions/interpretationOur data highlight the role of the degradation machinery in beta cell immunogenicity and emphasise the need for evaluation of targeted immunoproteasome inhibitors to limit beta cell destruction in type 1 diabetes.Data availabilityThe single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316).Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes
Conclusions/interpretationAltered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
An unwelcome inheritance: childhood obesity after diabetes in pregnancy
AbstractDiabetes in pregnancy affects 20 million women per year and is associated with increased risk of obesity in offspring, leading to insulin resistance and cardiometabolic disease. Despite the substantial public health ramifications, relatively little is known about the pathophysiological mechanisms underlying obesity in these high-risk children, which creates a barrier to successful intervention. While maternal glucose itself is undeniably a major stimulus upon intrauterine growth, the degree of offspring hyperinsulinism and disturbed lipid metabolism in mothers and offspring are also likely to be implicated in the d...
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
Cystine/glutamate antiporter System xc- deficiency impairs insulin secretion in mice
Conclusions/interpretationThese findings suggest that System xc- is required for glutathione maintenance and insulin production in beta cells and that the system is dispensable for islet macrophage function.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
Targeted serum proteomics of longitudinal samples from newly diagnosed youth with type 1 diabetes distinguishes markers of disease and C-peptide trajectory
Conclusions/interpretationThe association of several targeted proteins with fasting C-peptide/glucose levels in the first year after diagnosis suggests their connection with the underlying changes accompanying alterations in beta cell function in type 1 diabetes. Moreover, the direction of change in GPX3 during the first year was indicative of subsequent fasting C-peptide/glucose levels, and supports further investigation of this and other serum protein measurements in future studies of beta cell function in type 1 diabetes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
(Pre)diabetes and a higher level of glycaemic measures are continuously associated with corneal neurodegeneration assessed by corneal confocal microscopy: the Maastricht Study
Conclusions/interpretationTo our knowledge, this is the first population-based study to show that a more adverse glucose metabolism status and higher levels of glycaemic measures were all linearly associated with corneal neurodegeneration after adjustment for an extensive set of potential confounders. Our results indicate that glycaemia-associated corneal neurodegeneration is a continuous process that starts before the onset of type 2 diabetes. Further research is needed to investigate whether early reduction of hyperglycaemia can prevent corneal neurodegeneration.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
Glucose-lowering effects of a synbiotic combination containing Pediococcus acidilactici in C. elegans and mice
Conclusions/interpretationOur data suggest that the combination of pA1c with PC and BGC could be a potential synbiotic for blood glucose regulation and may help to fight insulin resistance, diabetes and obesity.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes
Conclusions/interpretation68Ga-DOTATATE uptake across the cardio –haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore,68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes.Trial registrationClinicalTrials.gov NCT05730634Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
