Daycare attendance, breastfeeding and risk of type 1 diabetes

Type 1 diabetes (T1D) is the most common serious chronic disease in children after allergies and asthma [1]. The incidence of T1D is increasing at an annual rate of about 3% [2]. It is expected that insulin will be difficult to access and afford in the future, especially in low-income countries [1]. Currently the lifetime costs of one subject with T1D diagnosed in childhood have been estimated to be about one million euros [1]. Furthermore, treatment of T1D requires ongoing glucose monitoring and causes continuous stress due to therapy, particularly for young children. Reducing T1D incidence would decrease personal stress and suffering of millions of children and their families as well as lead to major financial savings globally. T1D is an autoimmune disease where the pancreatic insulin-producing beta cells are destroyed by the immune system. It is likely that genetically susceptible individuals will not develop T1D without an external trigger that initiates the autoimmune response [3]. Although the autoimmune pathophysiology of T1D has been extensively studied, the understanding of the triggering environmental factors remains elusive [3]. The hygiene hypothesis states that the increase in incidence of T1D has resulted from reduced microbial exposure due to increased hygiene [4,5]. Contacts to a diverse microbial community early in life are proposed to activate regulatory pathways in the immune system. This process may prevent the development of T1D-associated autoimmunity. The number of social interactions is widely used as an estimate of the microbial exposure that the individual encounters [e.g., 6-8]. Daycare has been used in several studies as a proxy for the number of social interactions. A meta-analysis combining several case-control studies and three prospective cohort studies revealed a significant protective association of daycare with the risk of T1D [9]. However, the authors concluded that more prospective cohort studies are needed to allow general conclusions. The first few years of life is crucial in the development of the immune system and in the initiation of the T1D disease process [10]. Therefore, the daycare assignment age may play a role in the risk of developing T1D. However, this perspective has not been established in scientific research. Breastfeeding has also been shown to protect children from T1D [11]. Breastfeeding may protect an individual from infections by providing immune support through increased beta-cell proliferation and immunoglobulin A levels [12], and thus, reduce the risk of T1D. Hall et al. [13] found that daycare attendance was associated with increased T1D risk in non-breastfed children and a decreasing T1D risk with increasing breastfeeding duration. These preliminary results suggest that breastfeeding may modify the effect of daycare on T1D risk. Due to the very small number of children with T1D in that analysis cohort, the findings should be confirmed in larger series representing other populations. Research goals The overarching goal of this research project is to assess whether social interactions and breastfeeding are associated with the risk of T1D using the hygiene hypothesis as the theoretical framework and daycare as proxy for the number of social interactions. References 1. Mobasseri M, Shirmohammadi M, Amiri T, et al. Prevalence and incidence of type 1 diabetes in the world: a systematic review and meta-analysis. Health Promot Perspect 2020; 10: 98-115. 2. Aanstoot HJ, Anderson B, Daneman D, et al. The global burden of youth diabetes: perspectives and potential. Pediatr Diabetes 2007; 8: 1-44. 3. Knip M, Veijola R, Virtanen SM, et al. Environmental triggers and determinants of type 1 diabetes. Diabetes 2005; 54: 125-136. 4. Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299: 1259-60. 5. Bach JF, Chatenoud L. The hygiene hypothesis: an explanation for the increased frequency of insulin-dependent diabetes. Cold Spring Harb Perspect Med 2012; 2;4:a007799. 6. Schober E, Rami B, Waldhoer T. Small area variation in childhood diabetes mellitus in Austria: links to population density, 1989 to 1999. J Clin Epidemiol 2003; 56(3): 269-273. 7. McKinney PA, Okasha M, Parslow RC, et al. Early social mixing and childhood T1D mellitus: a case- control study in Yorkshire, UK. Diabet Med 2000; 3: 236-242. 8. Parslow RC, McKinney PA, Law GR, Bodansky HJ. Population mixing and childhood diabetes. Int J Epidemiol 2001; 30(3): 533-538. 9. Tall S, Virtanen SM, Knip M. Day Care Attendance and Risk of Type 1 Diabetes: A Meta-Analysis and Systematic Review. JAMA Pediatr. 2024 Dec 1;178(12):1290-1297. 10. Knip M, Luopajärvi K, Härkönen T. Early life origin of type 1 diabetes. Semin Immunopathol 2017; 39: 653-667. 11. Lampousi AM, Carlsson S, Löfvenborg JE. Dietary factors and risk of islet autoimmunity and type 1 diabetes: a systematic review and meta-analysis, EBioMedicine 2021; 72 103633. 12. Juto P. Human milk stimulates B cell function. Arch Dis Child 1985; 60: 610-613. 13. Hall K, Frederiksen B, Rewers M, et al. Daycare attendance, breastfeeding, and the development of T1D: the diabetes autoimmunity study in the young. Biomed Res Int 2015; 203947.