New research to be presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15-19 September) suggests that living in a rural environment in the first five years of life could increase the risk of developing type 1 diabetes compared with living in urban environments. The study is by Samy Sebraoui and Professor Soffia Gudbjornsdottir, University of Gothenburg, Sweden, and colleagues.
Type 1 diabetes (T1D) is a chronic autoimmune disease where the body's immune system mistakenly attacks and destroys insulin-producing cells in the pancreas, called beta cells. This leads to little to no insulin production, a hormone crucial for regulating blood sugar levels. Without sufficient insulin, glucose (sugar) builds up in the bloodstream, causing hyperglycaemia (high blood sugar). T1D is typically diagnosed in childhood, adolescence, or young adulthood, but can occur at any age. Most people with the condition quickly progress to needing insulin replacement therapy for the rest of their lives.
Sweden has the second highest global incidence of T1D, with geographical variation suggesting environmental risk factors. Previous studies have focused on patient location at diagnosis, and only very few at the time of birth or before clinical diagnoses. This new study explores T1D incidence in Sweden based on where people have lived over time, following patients from birth to diagnosis to identify high- and low-risk clusters over different life periods.
All patients diagnosed with T1D during 2005-2022 (ages 0-30 years) were identified in the Swedish National Diabetes Register. All residential addresses from birth to diagnosis were then identified by Statistics Sweden. Statistical analysis was used to identify significant high- and low-risk clusters (see figure). A technique known as zonal statistics analysis was used to identify the land use / land cover characteristics of all identified clusters for the first five years of life exposure window.
The researchers found that 21,774 patients aged 0 to 30 years were diagnosed with T1D 2005-2022, 58 % were male; and 15,426 (around three quarters) were under 18 years old at diagnosis. The mean age at diagnosis was 13.6 yrs (males 14.1, females 12.9). 24 % of patients had relocated to a different municipality from birth to diagnosis.
Based on the residential location of all patients at the diagnosis of type 1 diabetes, 4 significant high-risk clusters were identified, all located centrally in the country (all in the countryside, away from urban centres), where the relative risk of developing T1D was between 30% and 80% higher compared to what would be expected from national averages (Fig 1a). No high-risk clusters were observed in people in major cities.
On the contrary, significant low-risk clusters were found in the largest cities, where the risk of developing T1D was found to be 20% to 50% lower (within the largest cities such as Stockholm, Gothenburg and Malmö). The authors say: "This finding was unexpected and highlights the need for environmental studies to investigate potential risk factors in rural areas, as well as possible protective factors in urban settings. In Sweden, we have access to highly detailed environmental data covering the entire country, providing a unique opportunity to better understand the development of type 1 diabetes."
Then a second analysis, based on the main residential location during the first 5 years of life (regardless of age of diagnosis), 11 high-risk clusters were identified, all rural, with an increased risk of developing T1D of between 20% and 2.7 times higher compared with national averages. The northern regions had the highest relative risks. For the same time period, 15 low-risk clusters were observed, all in cities across the country, where risk of developing T1D was 20% to 88% lower than national averages - the very lowest risk being found in middle-sized cities in southern Sweden - (Fig 2b) – the cities with the lowest risk being Växjö (88% lower); Norrköping (64% lower) and Halmstad (61% lower).
The land use / land cover analysis conducted by the authors revealed notable differences between high- and low-risk clusters for the first 5 years of life. High-risk clusters are characterised by land covered by forest or used in agriculture, whereas low-risk clusters are dominated by urban and open land.
The authors say: "There is a clear geographical variation in the incidence of type 1 diabetes in Sweden. The first 5 years of life exhibited the strongest association with high- and low-risk clustering. Our findings facilitate further research into environmental factors potentially influencing development of type 1 diabetes. We hypothesise that the exposure of environmental factors, predominantly in rural areas and primarily during the first five years of life, elevates the risk for developing type 1 diabetes."
They discuss some possible theories that can be explored in future studies, saying: "Viral infections are more common in early life in urban areas and that could protect a person from future autoimmune diseases including type 1 diabetes. Living in rural areas could be associated with more exposure, for example, to pesticides and allergens. This is only speculation, but we have very good data to be able to investigate this in detail in future studies."
They conclude: "These findings were previously unknown and unexpected - it was a surprise that that living in larger cities came with a lower future risk of type 1 diabetes. We will study in detail different environmental factors that might be protective or increase risk. We will also look into different lifestyles in urban versus rural areas."
