Infant exposures and development of type 1 diabetes mellitus: The Diabetes Autoimmunity Study in the Young (DAISY).

IMPORTANCE The incidence of type 1 diabetes mellitus (T1DM) is increasing worldwide, with the most rapid increase among children younger than 5 years of age. OBJECTIVE To examine the associations between perinatal and infant exposures, especially early infant diet, and the development of T1DM. DESIGN The Diabetes Autoimmunity Study in the Young (DAISY) is a longitudinal, observational study. SETTING Newborn screening for human leukocyte antigen (HLA) was done at St. Joseph's Hospital in Denver, Colorado. First-degree relatives of individuals with T1DM were recruited from the Denver metropolitan area. PARTICIPANTS A total of 1835 children at increased genetic risk for T1DM followed up from birth with complete prospective assessment of infant diet. Fifty-three children developed T1DM. EXPOSURES Early (<4 months of age) and late (≥6 months of age) first exposure to solid foods compared with first exposures at 4 to 5 months of age (referent). MAIN OUTCOME AND MEASURE Risk for T1DM diagnosed by a physician. RESULTS Both early and late first exposure to any solid food predicted development of T1DM (hazard ratio [HR], 1.91; 95% CI, 1.04-3.51, and HR, 3.02; 95% CI, 1.26-7.24, respectively), adjusting for the HLA-DR genotype, first-degree relative with T1DM, maternal education, and delivery type. Specifically, early exposure to fruit and late exposure to rice/oat predicted T1DM (HR, 2.23; 95% CI, 1.14-4.39, and HR, 2.88; 95% CI, 1.36-6.11, respectively), while breastfeeding at the time of introduction to wheat/barley conferred protection (HR, 0.47; 95% CI, 0.26-0.86). Complicated vaginal delivery was also a predictor of T1DM (HR, 1.93; 95% CI, 1.03-3.61). CONCLUSIONS AND RELEVANCE These results suggest the safest age to introduce solid foods in children at increased genetic risk for T1DM is between 4 and 5 months of age. Breastfeeding while introducing new foods may reduce T1DM risk.

[1]  M. Kenward,et al.  Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group. , 1999, Diabetes care.

[2]  P. Juto Human milk stimulates B cell function. , 1985, Archives of disease in childhood.

[3]  L. Nyström,et al.  Birthweight and risk of type 1 diabetes in children and young adults: a population-based register study , 2005, Diabetologia.

[4]  C. Beaufort Incidence and trends of Childhood Type 1 diabetes worldwide 1990-1999 , 2006 .

[5]  M. Kenward,et al.  Early introduction of root vegetables in infancy associated with advanced ß‐cell autoimmunity in young children with human leukocyte antigen‐conferred susceptibility to Type 1 diabetes , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[6]  Michael K. Georgieff,et al.  Breastfeeding and the use of human milk , 1997 .

[7]  S. Virtanen,et al.  Early introduction of dairy products associated with increased risk of IDDM in Finnish children. The Childhood in Diabetes in Finland Study Group. , 1993 .

[8]  K. Brown WHO/UNICEF review on complementary feeding and suggestions for future research: WHO/UNICEF guidelines on complementary feeding. , 2000, Pediatrics.

[9]  G. Dahlquist,et al.  Intrauterine growth pattern and risk of childhood onset insulin dependent (type I) diabetes: population based case-control study , 1996, BMJ.

[10]  E. Carrasco,et al.  Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children , 1996, Journal of Molecular Medicine.

[11]  Dana Dabelea,et al.  The accelerating epidemic of childhood diabetes , 2009, The Lancet.

[12]  E. Negri,et al.  IDDM and Early Infant Feeding: Sardinian case-control study , 1997, Diabetes Care.

[13]  J. Tuomilehto,et al.  Worldwide increase in incidence of Type I diabetes – the analysis of the data on published incidence trends , 1999, Diabetologia.

[14]  Timing of Initial Exposure to Cereal Grains and the Risk of Wheat Allergy , 2006 .

[15]  L. J. Wei,et al.  Regression analysis of multivariate incomplete failure time data by modeling marginal distributions , 1989 .

[16]  E. Bonifacio,et al.  Cesarean Section and Interferon-Induced Helicase Gene Polymorphisms Combine to Increase Childhood Type 1 Diabetes Risk , 2011, Diabetes.

[17]  G. Dahlquist,et al.  A high linear growth is associated with an increased risk of childhood diabetes mellitus , 1992, Diabetologia.

[18]  Heather J Cordell,et al.  Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte antigen class II genotype: a population-based study in the United Kingdom. , 2004, The Journal of clinical endocrinology and metabolism.

[19]  A. Green,et al.  Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study , 2009, The Lancet.

[20]  M. Rewers,et al.  Early Exposure to Cow's Milk and Solid Foods in Infancy, Genetic Predisposition, and Risk of IDDM , 1993, Diabetes.

[21]  R. Kleinman,et al.  American Academy of Pediatrics recommendations for complementary feeding. , 2000, Pediatrics.

[22]  M. Rewers,et al.  Perinatal factors and development of islet autoimmunity in early childhood: the diabetes autoimmunity study in the young. , 2004, American journal of epidemiology.

[23]  Jaakko Tuomilehto,et al.  Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study , 2008, The Lancet.

[24]  R. T. Lie,et al.  Maternal and paternal age at delivery, birth order, and risk of childhood onset type 1 diabetes: population based cohort study , 2001, BMJ : British Medical Journal.

[25]  J. Norris Infant and Childhood Diet and Type 1 Diabetes Risk: Recent Advances and Prospects , 2010, Current diabetes reports.

[26]  P. Baghurst,et al.  Weight Gain in Early Life Predicts Risk of Islet Autoimmunity in Children With a First-Degree Relative With Type 1 Diabetes , 2009, Diabetes Care.

[27]  S. Virtanen,et al.  Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age. , 2003, The American journal of clinical nutrition.

[28]  M. Rewers,et al.  Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY) , 1996, Diabetologia.

[29]  M. Rewers,et al.  Timing of Initial Exposure to Cereal Grains and the Risk of Wheat Allergy , 2006, Pediatrics.

[30]  M. Atkinson Timing of initial cereal exposure in infancy and risk of islet autoimmunity. , 2004, The Journal of pediatrics.

[31]  J. Stockman,et al.  Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study , 2011 .

[32]  J. Todd,et al.  A genome-wide search for human type 1 diabetes susceptibility genes , 1994, Nature.

[33]  G. Dahlquist,et al.  Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group. , 1999, Diabetes care.

[34]  S. Virtanen,et al.  Early Introduction of Dairy Products Associated with Increased Risk of IDDM in Finnish Children , 1993, Diabetes.

[35]  G. Law,et al.  Perinatal and neonatal determinants of childhood type 1 diabetes. A case-control study in Yorkshire, U.K. , 1999, Diabetes care.

[36]  E. Bonifacio,et al.  Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. , 2003, JAMA.

[37]  B. Källén,et al.  Maternal-child blood group incompatibility and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus , 1992, Diabetologia.

[38]  A. Ivarsson,et al.  Breast-feeding protects against celiac disease. , 2002, The American journal of clinical nutrition.