Assessment of preservation of beta-cell function in children with long-standing type 1 diabetes with „ultrasensitive c-peptide” method

2017 ◽  
Vol 23 (3) ◽  
pp. 130-138 ◽  
Author(s):  
Agnieszka Kalinowska ◽  
◽  
Barbara Orlińska ◽  
Mateusz Panasiuk ◽  
Milena Jamiołkowska ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
C Peptide

scholarly journals Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e049595
Author(s):  
John W Gregory ◽  
Kymberley Carter ◽  
Wai Yee Cheung ◽  
Gail Holland ◽  
Jane Bowen-Morris ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Research Ethics ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Double Blind ◽  
C Peptide ◽  
New Onset

IntroductionMost individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysisThis is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.Ethics and disseminationThis trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences.Trial registration numberISRCTN14274380.

scholarly journals Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial

Gut ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 92-105 ◽  
Author(s):  
Pieter de Groot ◽  
Tanja Nikolic ◽  
Silvia Pellegrini ◽  
Valeria Sordi ◽  
Sultan Imangaliyev ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Healthy Donor ◽  
Cell Function ◽  
Plasma Metabolites ◽  
Faecal Microbiota ◽  
C Peptide ◽  
Small Intestinal

ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.

scholarly journals Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e033500 ◽  
Author(s):  
Charlotte Boughton ◽  
Janet M Allen ◽  
Martin Tauschmann ◽  
Sara Hartnell ◽  
Malgorzata E Wilinska ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Closed Loop ◽  
Cell Function ◽  
Insulin Delivery ◽  
Group Differences ◽  
C Peptide ◽  
Target Glucose

IntroductionManagement of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued intensive metabolic control using hybrid closed-loop (CL) insulin delivery following diagnosis of T1D can preserve C-peptide secretion, a marker of residual beta-cell function, compared with standard multiple daily injections (MDI) therapy.Methods and analysisThe study adopts an open-label, multicentre, randomised, parallel design, and aims to randomise 96 participants aged 10–16.9 years, recruited within 21 days of diagnosis with T1D. Following a baseline mixed meal tolerance test (MMTT), participants will be randomised to receive 24 months treatment with conventional MDI therapy or with CL insulin delivery. A further 24-month optional extension phase will be offered to all participants to continue with the allocated treatment. The primary outcome is the between group difference in area under the stimulated C-peptide curve (AUC) of the MMTT at 12 months post diagnosis. Analyses will be conducted on an intention-to-treat basis. Key secondary outcomes are between group differences in time spent in target glucose range (3.9–10 mmol/L), glycated haemoglobin (HbA1c) and time spent in hypoglycaemia (<3.9 mmol/L) at 12 months. Secondary efficacy outcomes include between group differences in stimulated C-peptide AUC at 24 months, time spent in target glucose range, glucose variability, hypoglycaemia and hyperglycaemia as recorded by periodically applied masked continuous glucose monitoring devices, total, basal and bolus insulin dose, and change in body weight. Cognitive, emotional and behavioural characteristics of participants and parents will be evaluated, and a cost–utility analysis performed to support adoption of CL as a standard treatment modality following diagnosis of T1D.Ethics and disseminationEthics approval has been obtained from Cambridge East Research Ethics Committee. The results will be disseminated by peer-reviewed publications and conference presentations.Trial registration numberNCT02871089; Pre-results.

294-OR: Type 1 Diabetes Patients with Residual Beta-Cell Function Display Improved Time in Euglycemia and Less Glycaemic Fluctuation after Exercise

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 294-OR
Author(s):  
GUY S. TAYLOR ◽  
KIERAN SMITH ◽  
JADINE SCRAGG ◽  
AYAT BASHIR ◽  
RICHARD A. ORAM ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Diabetes Patients

scholarly journals Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route

2020 ◽  
Vol 21 (5) ◽  
pp. 1598 ◽  
Author(s):  
Johnny Ludvigsson
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Human Subjects ◽  
Subcutaneous Administration ◽  
Acid Decarboxylase ◽  
Recent Onset ◽  
Prevention Trials

Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.

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