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 - September 30, 2023 Category: Endocrinology Source Type: research
Retinal inflammation in murine models of type 1 and type 2 diabetes with diabetic retinopathy
Conclusions/interpretationWe conclude that retinal inflammation is involved in and sustains pericyte loss as diabetic retinopathy progresses. Moreover, IFN γ plays a critical role in reducing pericyte survival in the retina by reducing activation of the PDGFRβ signalling pathway and increasing PKCδ levels and pericyte apoptosis.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 2023 Category: Endocrinology Source Type: research
Targeting BCAA metabolism to potentiate metformin ’s therapeutic efficacy in the treatment of diabetes in mice
Conclusions/interpretationMetformin self-limits its therapeutic efficacy in the treatment of type 2 diabetes by triggering the suppression of BCAA catabolism. Enhancing BCAA catabolism pharmacologically or reducing BCAA intake nutritionally potentiates the glucose-lowering effect of metformin. These data highlight the nutritional impact of protein on metformin ’s therapeutic efficacy and provide new strategies targeting BCAA metabolism to improve metformin’s effects on the clinical outcome in diabetes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 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 - September 30, 2023 Category: Endocrinology Source Type: research
Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes/diabetes in young women following pregnancy
Conclusion/interpretationDeclining beta cell function is the dominant determinant of incident prediabetes/diabetes in young women following pregnancy.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 30, 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 - September 30, 2023 Category: Endocrinology Source Type: research
Continuous glucose monitoring-derived time in range and CV are associated with altered tissue characteristics of the carotid artery wall in people with type 2 diabetes
Conclusions/interpretationTIR and CV were significantly associated with changes in the tissue characteristics of the carotid artery wall.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, number UMIN000032325Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 26, 2023 Category: Endocrinology Source Type: research
Presymptomatic type 1 diabetes and disease severity at onset
(Source: Diabetologia)
Source: Diabetologia - September 26, 2023 Category: Endocrinology Source Type: research
Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy
Conclusions/interpretationCutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 20, 2023 Category: Endocrinology Source Type: research
The challenges of identifying and studying type 1 diabetes in adults
AbstractDiagnosing type 1 diabetes in adults is difficult since type 2 diabetes is the predominant diabetes type, particularly with an older age of onset (approximately>30 years). Misclassification of type 1 diabetes in adults is therefore common and will impact both individual patient management and the reported features of clinically classified cohorts. In this article, we discuss the challenges associated with correctly identifying adult-onset type 1 diabetes and the implications of these challenges for clinical practice and research. We discuss how many of the reported differences in the characteristics of autoimmun...
Source: Diabetologia - September 20, 2023 Category: Endocrinology Source Type: research
Identifying the severity of diabetic retinopathy by visual function measures using both traditional statistical methods and interpretable machine learning: a cross-sectional study
Conclusions/interpretationEnsemble ML models predicted status of diabetic eye disease with high accuracy using just age, sex and measures of visual function. Interpretable ML methods enabled us to identify profiles of visual function associated with different stages of diabetic eye disease, and to disentangle associations from artefacts of the data collection process. Together, these two techniques have great potential for developing prediction models using untidy real-world clinical data.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 19, 2023 Category: Endocrinology Source Type: research
Presymptomatic type 1 diabetes and disease severity at onset. Reply to Schneider J, Gemulla G, Kiess W et al [letter]
(Source: Diabetologia)
Source: Diabetologia - September 19, 2023 Category: Endocrinology Source Type: research
Racial/ethnic and socioeconomic disparities in achievement of treatment goals within a clinical trial: a secondary analysis of the ACCORD trial
Conclusions/interpretationRacially/ethnically minoritised participants in the ACCORD trial were less likely to achieve high-burden (glycaemic) treatment goals but were generally similarly likely to achieve goals of less intensive interventions. Differences in glycaemic treatment goal achievement were partially mediated by differences in medication use but not mediated by hypoglycaemia, change in BMI or study visit attendance.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 16, 2023 Category: Endocrinology Source Type: research
Up Front
(Source: Diabetologia)
Source: Diabetologia - September 15, 2023 Category: Endocrinology Source Type: research
Quantifying beta cell function in the preclinical stages of type 1 diabetes
AbstractClinically symptomatic type 1 diabetes (stage 3 type 1 diabetes) is preceded by a pre-symptomatic phase, characterised by progressive loss of functional beta cell mass after the onset of islet autoimmunity, with (stage 2) or without (stage 1) measurable changes in glucose profile during an OGTT. Identifying metabolic tests that can longitudinally track changes in beta cell function is of pivotal importance to track disease progression and measure the effect of disease-modifying interventions. In this review we describe the metabolic changes that occur in the early pre-symptomatic stages of type 1 diabetes with resp...
Source: Diabetologia - September 15, 2023 Category: Endocrinology Source Type: research
