Early Childhood Infections Precede Development of Beta-Cell Autoimmunity and Type 1 Diabetes in Children With HLA-conferred Disease Risk

Pediatr Diabetes. 2018 Mar;19(2):293-299. doi: 10.1111/pedi.12547. Epub 2017 Jun 9.

Abstract

Background: The etiology of type 1 diabetes (T1D) is largely unknown. Infections and microbial exposures are believed to play a role in the pathogenesis and in the development of islet autoimmunity in genetically susceptible individuals.

Objective: To assess the relationships between early childhood infections, islet autoimmunity, and progression to T1D in genetically predisposed children.

Methods: Children with human leukocyte antigen (HLA)-conferred disease susceptibility (N=790; 51.5% males) from Finland (n = 386), Estonia (n = 322), and Russian Karelia (n = 82) were observed from birth up to the age of 3 years. Children attended clinical visits at the age of 3, 6, 12, 18, 24, and 36 months. Serum samples for analyzing T1D-associated autoimmune markers were collected and health data recorded during the visits.

Results: Children developing islet autoimmunity (n = 46, 5.8%) had more infections during the first year of life (3.0 vs 3.0, mean rank 439.1 vs 336.2; P = .001) and their first infection occurred earlier (3.6 vs 5.0 months; P = .005) than children with no islet autoimmunity. By May 2016, 7 children (0.9%) had developed T1D (progressors). Compared with non-diabetic children, T1D progressors were younger at first infection (2.2 vs 4.9 months; P = .004) and had more infections during the first 2 years of life (during each year 6.0 vs 3.0; P = .001 and P = .027, respectively). By 3 years of age, the T1D progressors had twice as many infections as the other children (17.5 vs 9.0; P = .006).

Conclusions: Early childhood infections may play an important role in the pathogenesis of T1D. Current findings may reflect either differences in microbial exposures or early immunological aberrations making diabetes-prone children more susceptible to infections.

Keywords: childhood infections; islet autoimmunity; respiratory tract infections; the hygiene hypothesis; type 1 diabetes.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmunity*
  • Child Development*
  • Cohort Studies
  • Community-Acquired Infections / blood
  • Community-Acquired Infections / epidemiology
  • Community-Acquired Infections / genetics
  • Community-Acquired Infections / immunology*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression
  • Disease Susceptibility
  • Estonia / epidemiology
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • HLA-DR Antigens / chemistry
  • HLA-DR Antigens / genetics
  • Humans
  • Infant, Newborn
  • Insulin-Secreting Cells / immunology*
  • Male
  • Prediabetic State / blood
  • Prediabetic State / genetics
  • Prediabetic State / immunology*
  • Prediabetic State / physiopathology
  • Prospective Studies
  • Respiratory Tract Infections / blood
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / genetics
  • Respiratory Tract Infections / immunology*
  • Risk
  • Russia / epidemiology

Substances

  • HLA-DR Antigens