Abstract
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.
Highlights
An estimated 1.1 million people under 20 years of age are affected by type 1 diabetes (T1D) worldwide [1, 2]
A study demonstrated that RV infection prior to 6 months of age was significantly associated with human and bovine-insulin binding antibodies, but this was strongest in children receiving cow’s milk prior to 3 months [62], representing an important confounding factor
In the Finnish TRIGR study, genetically susceptible children were randomised to either cow’s milk (CM) or casein-hydrosylate formula (CHF) feed, during the first 6-8 months of life where breast feeding was not possible, and found a reduced incidence of islet autoimmunity (IA) in the CHF group compared to CM group, with one [HR 0.51 (0.28-0.91)] or ≥two autoantibody positivity [HR 0.47 (0.191.07)] [154]
Summary
An estimated 1.1 million people under 20 years of age are affected by type 1 diabetes (T1D) worldwide [1, 2]. Environmental Determinants of Type 1 Diabetes exogenous insulin [10] This provides different targets for prevention at the stages of primary prevention (preventing seroconversion, in those genetically at risk), and secondary prevention (preventing loss of and damage to the beta-cells in individuals with autoimmunity/autoantibodies) [12]. Some of these reviews predate the results of the seminal, ‘The Environmental Determinants of Diabetes in the Young’ (TEDDY) study, from which different aspects have been published over the last 6 years [26] In this narrative review, we explore the putative environmental risk factors for T1D with an emphasis on testing causality.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
