scholarly journals Environmental Determinants of Type 1 Diabetes: From Association to Proving Causality

2021 ◽  
Vol 12 ◽  
Author(s):  
Lauren M. Quinn ◽  
F. Susan Wong ◽  
Parth Narendran
Keyword(s):  
Type 1 Diabetes ◽  
Search Strategy ◽  
Supporting Evidence ◽  
Health Prevention ◽  
Prevention Strategies ◽  
Environmental Determinants ◽  
Rapid Weight Gain ◽  
Rising Incidence ◽  
Randomised Controlled

The rising incidence of type 1 diabetes (T1D) cannot be ascribed to genetics alone, and causative environmental triggers and drivers must also be contributing. The prospective TEDDY study has provided the greatest contributions in modern time, by addressing misconceptions and refining the search strategy for the future. This review outlines the evidence to date to support the pathways from association to causality, across all stages of T1D (seroconversion to beta cell failure). We focus on infections and vaccinations; infant growth and childhood obesity; the gut microbiome and the lifestyle factors which cultivate it. Of these, the environmental determinants which have the most supporting evidence are enterovirus infection, rapid weight gain in early life, and the microbiome. We provide an infographic illustrating the key environmental determinants in T1D and their likelihood of effect. The next steps are to investigate these environmental triggers, ideally though gold-standard randomised controlled trials and further prospective studies, to help explore public health prevention strategies.

scholarly journals Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial

Diabetologia ◽  
2021 ◽  
Author(s):  
Robin Assfalg ◽  
Jan Knoop ◽  
Kristi L. Hoffman ◽  
Markus Pfirrmann ◽  
Jose Maria Zapardiel-Gonzalo ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Antibody Responses ◽  
Oral Insulin ◽  
Cell Responses ◽  
Randomised Controlled

Abstract Aims/hypothesis Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome. Methods A phase I/II randomised controlled trial was performed in a single clinical study centre in Germany. Participants were 44 islet autoantibody-negative children aged 6 months to 2.99 years who had a first-degree relative with type 1 diabetes and a susceptible HLA DR4-DQ8-containing genotype. Children were randomised 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months using a web-based computer system. The primary outcome was immune efficacy pre-specified as induction of antibody or T cell responses to insulin and measured in a central treatment-blinded laboratory. Results Randomisation was performed in 44 children. One child in the placebo group was withdrawn after the first study visit and data from 22 insulin-treated and 21 placebo-treated children were analysed. Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in children who received both insulin (54.5%) and placebo (66.7%), and the trial did not demonstrate an effect on its primary outcome (p = 0.54). In exploratory analyses, there was preliminary evidence that the immune response and gut microbiome were modified by the INS genotype Among children with the type 1 diabetes-susceptible INS genotype (n = 22), antibody responses to insulin were more frequent in insulin-treated (72.7%) as compared with placebo-treated children (18.2%; p = 0.03). T cell responses to insulin were modified by treatment-independent inflammatory episodes. Conclusions/interpretation The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptible INS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells. Trial registration Clinicaltrials.gov NCT02547519 Funding The main funding source was the German Center for Diabetes Research (DZD e.V.) Graphical abstract

scholarly journals Closed-loop glucose control in young people with type 1 diabetes during and after unannounced physical activity: a randomised controlled crossover trial

Diabetologia ◽  
2017 ◽  
Vol 60 (11) ◽  
pp. 2157-2167 ◽  
Author(s):  
Klemen Dovc ◽  
Maddalena Macedoni ◽  
Natasa Bratina ◽  
Dusanka Lepej ◽  
Revital Nimri ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 1 Diabetes ◽  
Young People ◽  
Glucose Control ◽  
Closed Loop ◽  
Crossover Trial ◽  
Randomised Controlled

scholarly journals Cost-effectiveness of home versus hospital management of children at onset of type 1 diabetes: the DECIDE randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043523
Author(s):  
Zoe McCarroll ◽  
Julia Townson ◽  
Timothy Pickles ◽  
John W Gregory ◽  
Rebecca Playle ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cost Effectiveness ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Case Analysis ◽  
Base Case ◽  
Base Case Analysis ◽  
Home Management ◽  
Randomised Controlled

ObjectiveThe aim of this economic evaluation was to assess whether home management could represent a cost-effective strategy in the patient pathway of type 1 diabetes (T1D). This is based on the Delivering Early Care In Diabetes Evaluation trial (ISRCTN78114042), which compared home versus hospital management from diagnosis in childhood diabetes and found no statistically significant difference in glycaemic control at 24 months.DesignCost-effectiveness analysis alongside a randomised controlled trial.SettingEight paediatric diabetes centres in England, Wales and Northern Ireland.Participants203 clinically well children aged under 17 years, with newly diagnosed T1D and their carers.Outcome measuresThe base-case analysis adopted n National Health Service (NHS) perspective. A scenario analysis assessed costs from a broader societal perspective. The incremental cost-effectiveness ratio (ICER), expressed as cost per mmol/mol reduction in glycated haemoglobin (HbA1c), was based on the mean difference in costs between the home and hospital groups, divided by mean differences in effectiveness (HbA1c). Uncertainty was considered in terms of the probability of cost-effectiveness.ResultsAt 24 months postintervention, the base-case analysis showed a difference in costs between home and hospital, in favour of home management (mean difference −£2,217; 95% CI −£2825 to −£1,609; p<0.001). Home care dominated, with an ICER of £7434 (saved) per mmol/mol reduction of HbA1c. The results of the scenario analysis also favoured home management. The greatest driver of cost differences was hospitalisation during the initiation period.ConclusionsHome management from diagnosis of children with T1D who are medically stable represents a less costly approach for the NHS in the UK, without impacting clinical effectiveness.Trial registration numberISRCTN78114042.

Sign in / Sign up

Export Citation Format

Share Document