Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4 T cells.

Type 1 diabetes (T1D) is an autoimmune disease that develops when T cells destroy the insulin-producing beta cells that reside in the pancreatic islets. Immune cells, including T cells, infiltrate the islets and gradually destroy the beta cells. Human islet-infiltrating CD4 T cells recognize peptide epitopes derived from proinsulin, particularly C-peptide.

A minority of proliferating human CD4 T cells in antigen-driven proliferation assays are antigen specific.

Antigen-driven T-cell proliferation is often measured using fluorescent dye dilution assays, such as the CFSE-based proliferation assay. Dye dilution assays have been powerful tools to detect human CD4 T-cell responses, particularly against autoantigens. However, it is not known how many cells within the proliferating population are specific for the stimulating antigen.

Glycemic and Psychosocial Outcomes of Advanced Hybrid Closed-Loop Therapy in Youth With High HbA1c: A Randomized Clinical Trial.

Objective: To determine the efficacy of advanced hybrid closed-loop (AHCL) therapy in a high-risk cohort of youth on continuous subcutaneous insulin infusion (CSII) with or without continuous glucose monitoring (CGM) with suboptimal glycemia.

Research Design And Methods: In a 6-month multicenter clinical trial, youth with type 1 diabetes with mean and most recent HbA1c >8.5% (65 mmol/mol) were randomly assigned 1:1 to AHCL or treatment as usual (CSII ± CGM).

Correlation between centre size, metabolic variation and mean HbA1c in major paediatric diabetes centres.

Aim: To exploit a relatively homogeneous national health care context and a national diabetes database to address the questions: Is there an optimal clinic/centre size in determining outcomes?; and Can improvement in median centre outcomes be driven by reducing variability in outcome?

Methods: Using the Australasian Diabetes Database Network, data from seven tertiary hospital paediatric diabetes clinics for patients with type one diabetes from Australia were recorded from 6-month uploads: September 2017, March 2018, September 2018 and March 2019. Data from 25 244 patient visits included demographic variables, HbA1C, number of patient visits and insulin regimens.

Results: There was no association between centre size and median HbA1C.

Does insulin pump therapy offer benefits for behaviour, mood, cognition and HbA1c in children and adolescents with type 1 diabetes? A randomised controlled trial with observational follow-up.

Aims: Improved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these findings in a randomised controlled trial (RCT), with longitudinal follow-up.

Methods: RCT of youth aged 7-15 years with T1D, at two tertiary paediatric centres.

Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data.

Background: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations.

Methods: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK).

Adolescent ambivalence about diabetes technology-The Janus faces of automated care.

The Janus face metaphor approach highlights that a technology may simultaneously have two opposite faces or properties with unforeseen paradoxes within human-technology interaction. Suboptimal acceptance and clinical outcomes are sometimes seen in adolescents who use diabetes-related technologies. A traditional linear techno-determinist model of technology use would ascribe these unintended outcomes to suboptimal technology, suboptimal patient behavior, or suboptimal outcome measures.

Decreased occurrence of ketoacidosis and preservation of beta cell function in relatives screened and monitored for type 1 diabetes in Australia and New Zealand.

Aims: Islet autoantibody screening of infants and young children in the Northern Hemisphere, together with semi-annual metabolic monitoring, is associated with a lower risk of ketoacidosis (DKA) and improved glucose control after diagnosis of clinical (stage 3) type 1 diabetes (T1D). We aimed to determine if similar benefits applied to older Australians and New Zealanders monitored less rigorously.

Methods: DKA occurrence and metabolic control were compared between T1D relatives screened and monitored for T1D and unscreened individuals diagnosed in the general population, ascertained from the Australasian Diabetes Data Network.

Effect of a Hybrid Closed-Loop System on Glycemic and Psychosocial Outcomes in Children and Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Hybrid closed-loop (HCL) therapy has improved glycemic control in children and adolescents with type 1 diabetes; however, the efficacy of HCL on glycemic and psychosocial outcomes has not yet been established in a long-term randomized clinical trial.

Objective: To determine the percentage of time spent in the target glucose range using HCL vs current conventional therapies of continuous subcutaneous insulin infusion or multiple daily insulin injections with or without continuous glucose monitoring (CGM).

Design, Setting, And Participants: This 6-month, multicenter, randomized clinical trial included 172 children and adolescents with type 1 diabetes; patients were recruited between April 18, 2017, and October 4, 2019, in Australia.

T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8.

HLA-DQ8, a genetic risk factor in type I diabetes (T1D), presents hybrid insulin peptides (HIPs) to autoreactive CD4+ T cells. The abundance of spliced peptides binding to HLA-DQ8 and how they are subsequently recognised by the autoreactive T cell repertoire is unknown. Here we report, the HIP (GQVELGGGNAVEVLK), derived from splicing of insulin and islet amyloid polypeptides, generates a preferred peptide-binding motif for HLA-DQ8.

Neural differentiation medium for human pluripotent stem cells to model physiological glucose levels in human brain.

Cortical neurospheres (NSPs) derived from human pluripotent stem cells (hPSC), have proven to be a successful platform to investigate human brain development and neuro-related diseases. Currently, many of the standard hPSC neural differentiation media, use concentrations of glucose (approximately 17.5-25 mM) and insulin (approximately 3.

Has subsidized continuous glucose monitoring improved outcomes in pediatric diabetes?

Introduction: In 2017, the Australian Federal Government fully subsidized continuous glucose monitoring (CGM) devices for patients under 21 years of age with T1D with the aim of reducing rates of severe hypoglycaemia (SH) and improving metabolic control. The aim of this study was to reports on metabolic outcomes in youth from a single tertiary centre.

Methods: The study design was observational.

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes.

Objectives: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D.

Methods: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.

Effect of frequency of sensor use on glycaemic control in individuals on sensor-augmented pump therapy with and without Predictive Low Glucose Management System.

Improved frequency of sensor use improves glycaemic control. Furthermore, there is no deterioration of glycaemic control with increased sensor use in individuals on Predictive Low Glucose Management (PLGM) system. Younger children are more likely to have better sensor uptake than older children.

The effect of type 1 diabetes on the developing brain.

The effect of type 1 diabetes on the developing brain is a topic of primary research interest. A variety of potential dysglycaemic insults to the brain can cause cellular and structural injury and lead to altered neuropsychological outcomes. These outcomes might be subtle in terms of cognition but appear to persist into adult life.

Characteristics of Automated Insulin Suspension and Glucose Responses with the Predictive Low-Glucose Management System.

Background: The Predictive Low-Glucose Management (PLGM) system suspends basal insulin when hypoglycemia is predicted and reduces hypoglycemia. The aim of this analysis was to explore the characteristics of automated insulin suspension and sensor glucose (SG) responses following PLGM-initiated pump suspension.

Research Design And Methods: Children and adolescents with type 1 diabetes used the Medtronic MiniMed™ 640G pump as part of a randomized controlled trial.

NR5A1 gene variants repress the ovarian-specific WNT signaling pathway in 46,XX disorders of sex development patients.

Several recent reports have described a missense variant in the gene NR5A1 (c.274C>T; p.Arg92Trp) in a significant number of 46,XX ovotesticular or testicular disorders of sex development (DSDs) cases.

Two's company, is three a crowd? Ethical cognition in decision making and the role of industry third parties in pediatric diabetes care.

Families of children with diabetes increasingly obtain health information from a variety of sources. Doctor-patient relationships have accordingly become more fluid and dynamic with input from other parties. These outside parties include representatives from the diabetes health care industry-industry third parties (ITPs).