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.

Extrapancreatic autoantibody profiles in type I diabetes.

Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel.

rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.

Objective: To evaluate UBASH3A (rs11203203) as a predictor of persistent islet autoimmunity (IA) and type 1 diabetes (T1D).

Research Design And Methods: The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D. The DAISY participants were genotyped for rs11202203 (UBASH3A).

Age of islet autoantibody appearance and mean levels of insulin, but not GAD or IA-2 autoantibodies, predict age of diagnosis of type 1 diabetes: diabetes autoimmunity study in the young.

Objective: We evaluated predictors of progression to diabetes in children with high-risk HLA genotypes and persistent islet autoantibodies.

Research Design And Methods: The Diabetes Autoimmunity Study in the Young (DAISY) followed 2,542 children with autoantibodies measured to GAD, IA-2, and insulin.

Results: Persistent islet autoantibodies developed in 169 subjects, and 55 of those progressed to diabetes.

Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY).

Objective: To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies.

Research Design And Methods: Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3-6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes.

Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?

Objective: Specific alleles of non-HLA genes INS, CTLA-4, and PTPN22 have been associated with type 1 diabetes. We examined whether some of these alleles influence development of islet autoimmunity or progression from persistent islet autoimmunity to type 1 diabetes in children with high-risk HLA-DR,DQ genotypes.

Research Design And Methods: Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,449 young children carrying HLA-DR,DQ genotypes associated with type 1 diabetes.

Dietary glycemic index, development of islet autoimmunity, and subsequent progression to type 1 diabetes in young children.

Context: Dietary factors may trigger or exacerbate the autoimmune disease process.

Objective: Our objective was to examine dietary glycemic index (GI) and glycemic load (GL) for association with islet autoimmunity (IA) development, and progression from IA to type 1 diabetes.

Design: The Diabetes Autoimmunity Study in the Young follows children at increased genetic type 1 diabetes risk.

Maternal diet during pregnancy and islet autoimmunity in offspring.

Background: Recent studies on the etiology of type 1 diabetes mellitus (T1DM) suggest that the components of the infant diet are associated with islet autoimmunity (IA), a precursor of T1DM. The role of prenatal nutritional exposures has not been thoroughly investigated.

Methods: The Diabetes Autoimmunity Study in the Young has enrolled newborns from 1993 to 2004 at increased risk for T1DM based on human leukocyte antigen (HLA) genotype and family history of T1DM.

Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes.

Context: Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study.

Objective: To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children.

Design, Setting, And Participants: A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes.

HLA-DPB1*0402 protects against type 1A diabetes autoimmunity in the highest risk DR3-DQB1*0201/DR4-DQB1*0302 DAISY population.

Objective: A major goal in genetic studies of type 1A diabetes is prediction of anti-islet autoimmunity and subsequent diabetes in the general population, as >85% of patients do not have a first-degree relative with type 1A diabetes. Given prior association studies, we hypothesized that the strongest candidates for enhancing diabetes risk among DR3-DQB1*0201/DR4-DQB1*0302 individuals would be alleles of DP and DRB1*04 subtypes and, in particular, the absence of reportedly protective alleles DPB1*0402 and/or DRB1*0403.

Research Design And Methods: We genotyped 457 DR3-DQB1*0201/DR4-DQB1*0302 Diabetes Autoimmunity Study of the Young (DAISY) children (358 general population and 99 siblings/offspring of type 1 diabetic patients) at the DPB1, DQB1, and DRB1 loci using linear arrays of immobilized sequence-specific oligonucleotides, with direct sequencing to differentiate DRB1*04 subtypes.

Association of the PTPN22/LYP gene with type 1 diabetes.

Objectives: The goal of this study was to verify the association between type 1 diabetes (T1D) and the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene in non-Hispanic whites (NHWs) and Hispanics from Colorado.

Subjects And Methods: The C1858T single-nucleotide polymorphism within the PTPN22 gene was genotyped in 753 patients with T1D ascertained from the diabetes clinic at the Barbara Davis Center in Denver and 662 control population.

Results: Both the PTPN22 CT genotype [odds ratio (OR) = 1.

Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY).

Objective: The aim of this study was to assess the utility of hemoglobin A1c (HbA1c) measurements in the early detection of clinical type 1 diabetes during prospective follow-up of children with islet autoimmunity.

Methods: The Diabetes Autoimmunity Study in the Young (DAISY) has followed for development of islet autoimmunity and diabetes general population newborns carrying human leukocyte antigen (HLA) genotypes conferring risk for type 1 diabetes and young siblings or offspring of people with type 1 diabetes. Testing for autoantibodies was performed at least once in 2234 and twice or more in 1887 children.

Extreme genetic risk for type 1A diabetes.

Type 1A diabetes (T1D) is an autoimmune disorder the risk of which is increased by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)].

Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease.

Context: While gluten ingestion is responsible for the signs and symptoms of celiac disease, it is not known what factors are associated with initial appearance of the disease.

Objective: To examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA).

Design, Setting, And Patients: Prospective observational study conducted in Denver, Colo, from 1994-2004 of 1560 children at increased risk for celiac disease or type 1 diabetes, as defined by possession of either HLA-DR3 or DR4 alleles, or having a first-degree relative with type 1 diabetes.

Secondary attack rate of type 1 diabetes in Colorado families.

Objective: Families of children diagnosed with type 1 diabetes require counseling concerning type 1 diabetes risk in nondiabetic siblings and parents. No U.S.

Elevated C-reactive protein levels in the development of type 1 diabetes.

Elevated C-reactive protein (CRP) levels have previously been described before the onset of type 2 diabetes and gestational diabetes. We hypothesized that inflammation, as reflected by elevated CRP levels, can help predict development of islet autoimmunity or type 1 diabetes. Children at risk for type 1 diabetes and followed in the Diabetes Autoimmunity Study of the Young (DAISY) had blood samples drawn and frozen serum saved at various intervals after birth.

Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY).

Diabetes Autoimmunity Study in the Young (DAISY) has followed 1972 children for islet autoimmunity and diabetes: 837 first-degree relatives of persons with type 1 diabetes and 1135 general population newborns identified through human leukocyte antigen (HLA) screening. During follow-up of 4.06 yr (range, 0.

Perinatal factors and development of islet autoimmunity in early childhood: the diabetes autoimmunity study in the young.

The objective of this study was to test whether maternal age at delivery, child's birth order, cesarean section, complicated delivery, maternal smoking during pregnancy, or neonatal jaundice predict islet autoimmunity in children at genetically increased risk of type 1 diabetes in a birth cohort with blood draws at ages 9, 15, and 24 months and yearly thereafter. Newborns with diabetes-associated human leukocyte antigen genotypes (n = 938) and offspring or siblings of persons with type 1 diabetes (n = 428) from the Denver, Colorado, metropolitan area were examined from January 1994 to February 2003. Information on perinatal factors was collected by using questionnaires soon after the birth.

Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up.

Objective: The objective of this study was to determine whether earlier diagnosis of diabetes in prospectively followed autoantibody-positive children lowered onset morbidity and improved the clinical course after diagnosis.

Research Design And Methods: The Diabetes Autoimmunity Study in the Young (DAISY) follows genetically at-risk children for the development of diabetes. Increased genetic risk is identified by family history of type 1 diabetes or expression of diabetes-associated HLA genotypes.

Clinical features of children with screening-identified evidence of celiac disease.

Objective: At-risk groups commonly undergo screening for autoantibodies associated with celiac disease (CD). However, the clinical significance of a positive test remains uncertain. The objective of this study was to evaluate growth and clinical features of children who test positive for an autoantibody associated with CD.

Fluctuating transglutaminase autoantibodies are related to histologic features of celiac disease.

Background & Aims: Asymptomatic children at risk for celiac disease (CD) and seropositive for immunoglobulin A anti-TG autoantibodies (TGAA) may lack small intestinal mucosal changes characteristic of CD. We have followed a group of children with serial testing for TGAA.

Methods: Subjects were a group of at-risk children comprised of infants expressing HLA-DR3 on newborn screening, those with type 1A diabetes, or a first-degree relative of someone with type 1 diabetes.

Is presence of islet autoantibodies at birth associated with development of persistent islet autoimmunity? The Diabetes Autoimmunity Study in the Young (DAISY).

Objective: To determine whether the presence of islet autoantibodies in the umbilical cord blood is predictive of subsequent development of islet autoimmunity.

Research Design And Methods: Cord blood sera from 1,118 subjects from the Diabetes Autoimmunity Study in the Young (DAISY) cohort, as well as their venous blood samples taken at follow-up clinic visits, were tested for GAD65 autoantibodies (GAAs), insulin autoantibodies (IAAs), and IA-2 autoantibodies (IA-2As). Venous blood samples taken from mothers of cord blood autoantibody-positive children were analyzed for the same autoantibodies.

Symptoms of common maternal infections in pregnancy and risk of islet autoimmunity in early childhood.

Objective: The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes.

Research Design And Methods: A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age View Article and Find Full Text PDF

Timing of initial cereal exposure in infancy and risk of islet autoimmunity.

Context: Dietary exposures in infancy have been implicated, albeit inconsistently, in the etiology of type 1 diabetes mellitus (DM).

Objective: To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA).

Design: Birth cohort study conducted from 1994 to 2002 with a mean follow-up of 4 years.

A prospective study of the incidence of childhood celiac disease.

Objectives: To estimate the frequency of celiac disease (CD) in children in the general population of Denver, Colorado.

Study Design: From 22,346 newborns characterized as expressing 0, 1, or 2 HLA-DR3(DQB1*0201) alleles, 987 were selected for a prospective stratified cohort study. Participants were followed for as long as 7 years with serial testing for serum IgA anti-transglutaminase antibodies and for evidence of CD (intestinal mucosal changes or persistent seropositivity).