The eaten exposome: findings in type 1 diabetes
The increasing incidence of type 1 diabetes has caused concern in the Western world during recent decades. Type 1 diabetes is an immune-mediated disease and genetics and environment, including diet, microbial infections and other factors, all are suspected to have a role in disease development. Exposure to these non-genetic environmental factors is called the exposome. In this post we attempt to gather current evidence about the role of diet in the development of type 1 diabetes and its preclinical state, islet autoimmunity, and discuss how diet could affect the risk. In the end, we highlight HEDIMED’s own research efforts in the field.
Nutritional factors associated with type 1 diabetes
Current evidence of the role of diet in the development of type 1 diabetes is mostly based on observational studies in children with genetic susceptibility to type 1 diabetes. In these studies, intake of each food and nutrient have based on regular diets. The researchers aimed not to change the diets of the children or parents. These studies have identified some dietary factors that seem to increase the risk of type 1 diabetes and some that seem to decrease the risk.1,2
Higher cow’s milk consumption in early childhood has been linked to increased risk of developing type 1 diabetes or islet autoimmunity. On the other hand, breastfeeding and sufficient vitamin D status have shown protective associations in some but not all studies.1,2 Additionally, long-chain omega-3 fatty acids have been linked to decreased risk of developing islet autoimmunity and this is supported by new research too. 1,3 Also, the age of introduction of foods may play a role in disease development. 1,2 Nevertheless, based on these observational studies, no threshold values for food consumption can be set.
Suggested mechanisms behind the findings
There might be multiple ways how early diet could modulate the risk of type 1 diabetes. The food components can directly stimulate the disease process or modulate gut microbiota, gut permeability and immune system. There is probably also some unknown mechanisms. 1
It has been suggested that the protein structure of cow’s milk may contribute to the risk of type 1 diabetes development by activating abnormal immune reaction in susceptible children. On the other hand, omega-3 fatty acids, breastmilk, and vitamin D may help sustain more controlled immune responses and inflammatory reactions to potential triggers such as dietary triggers and viral infections. These potentially protective nutrients could also beneficially affect the colonization and homeostasis of gut commensals and decrease gut permeability.1
One large randomized controlled trial (TRIGR study) tested the cow’s milk protein hypothesis: However, weaning to a hydrolyzed infant formula compared to a traditional cow’s milk-based formula did not reduce the cumulative incidence of type 1 diabetes in infants at risk.4
Dietary recommendations and type 1 diabetes prevention
Overall, the existing knowledge is not enough to give nutritional recommendations to prevent type 1 diabetes. The consistency of research results is not sufficient and there is also a lack of dietary intervention studies (randomized controlled trials) to establish recommendations.
However, it can be noticed that many of the presented research results are in line with current nutritional guidelines such as recommendations for omega-3 fatty acids, vitamin D, and breastfeeding. Still, there are also some controversial factors such as cow’s milk, which is now recommended for children, and has been associated with increased risk of type 1 diabetes. These associations must be investigated more, and it is too early to change the current recommendations in this respect.
The challenging exposome
Exposome research in general, as well as nutrition research, is challenging because there are multiple factors affecting simultaneously trough different pathways. Also, the time between exposure and the outcome is mainly long and differs one-to-one. The development of type 1 diabetes appears to be influenced by several risk factors, many of which are neither necessary nor sufficient to cause the disease alone. These several factors include a combination of decreased exposure to risk-lowering factors and increased exposure to risk-increasing ones. 5
The identification of the key factors contributing to the disease development could have an enormous prevention potential both on individual and societal level. Yet, the complexity of the disease development and its research makes it unlikely to achieve any rapid cure to the problem. Therefore, more research will be needed to decrease the burden of disease.
Paving the way towards new knowledge
HEDIMED has a strong focus on type 1 diabetes research among other immune-mediated diseases, primarily asthma, allergies, and celiac disease. Some top researchers with expertise in the field are working in the consortium. In HEDIMED, we aim to use the existing knowledge and utilize it in new, wide research interests. Nutrition is considered as one key exposomic factor in the development of diseases. Our researchers working in several countries and cohorts enable the combination of different data and maximize the potential in finding associations between nutritional factors and immune-mediated diseases.
One of HEDIMED’s aims is to investigate whether some certain factors are associated to all or just some of the diseases. HEDIMED also aims to research diet-disease associations simultaneously in several cohorts. In addition, researchers explore whether the known dietary factors interact with other exposomic factors such as infections. This kind of knowledge is one of a kind in the mapping of the exposome and paving the way towards new preventive medicine and improvement of public health.
Authors:
Framework and background information: Leena Hakola
Draft and writing: Henna Numminen, Leena Hakola & Minna Turppa
Editing: Leena Hakola, Suvi Virtanen, Aili Tagoma & Minna Turppa
References:
1. Niinistö, S., Hakola, L., Miettinen, M., & Virtanen, S. (2018). Varhainen ravitsemus vaikuttaa tyypin 1 diabeteksen kehittymiseen. Duodecim 2018;134(16):1577-84.
2. Lampousi, A-M., Carlsson, S. & Löfvenborg, J.E. 2021. Dietary factors and risk of islet autoimmunity and type 1 diabetes: a systematic review and meta-analysis. eBio Medicine, Volume 72; 103633. https://doi.org/10.1016/j.ebiom.2021.103633
3. Hakola, L., Vuorinen, AL., Takkinen, HM. et al. Dietary fatty acid intake in childhood and the risk of islet autoimmunity and type 1 diabetes: the DIPP birth cohort study. European journal of Nutrition (2022). https://doi.org/10.1007/s00394-022-03035-2
4. Writing Group for the TRIGR Study Group. 2018. Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial. JAMA. 2018;319(1):38–48. doi:10.1001/jama.2017.19826
5. Norris, J. M., Johnson, R. K., & Stene, L. C. (2020). Type 1 diabetes—Early life origins and changing epidemiology. The lancet Diabetes & endocrinology, 8(3), 226-238.
Picture references:
All the pictures have been downloaded from pexels.com
Picture 1. Photographer: Stephen Andrews
Picture 2. Photographer: Maria Verkhoturtseva
Picture 3: Photographer: Gustavo Fring
Picture 4: Photographer: Letticia Massari
Cover picture: Photographer: Alex Green
