The goal was to examine the relationship between age at the introduction of solid foods during the first year of life and allergic sensitization in 5-year-old children.
We analyzed data from the Finnish Type 1 Diabetes Prediction and Prevention nutrition study, a prospective, birth cohort study. We studied 994 children with HLA-conferred susceptibility to type 1 diabetes mellitus for whom information on breastfeeding, age at the introduction of solid foods, and allergen-specific immunoglobulin E levels at 5 years was available. The association between age at the introduction of solid foods and allergic sensitization was analyzed by using logistic regression.
The median duration of exclusive breastfeeding was 1.8 months (range: 0-10 months). After adjustment for potential confounders, late introduction of potatoes (>4 months), oats (>5 months), rye (>7 months), wheat (>6 months), meat (>5.5 months), fish (>8.2 months), and eggs (>10.5 months) was significantly directly associated with sensitization to food allergens. Late introduction of potatoes, rye, meat, and fish was significantly associated with sensitization to any inhalant allergen. In models that included all solid foods that were significantly related to the end points, eggs, oats, and wheat remained the most important foods related to sensitization to food allergens, whereas potatoes and fish were the most important foods associated with inhalant allergic sensitization. We found no evidence of reverse causality, taking into account parental allergic rhinitis and asthma.
Late introduction of solid foods was associated with increased risk of allergic sensitization to food and inhalant allergens.
A third of parents suspect food allergy in their children. Questionnaire-based studies usually overestimate the occurrence of food allergies. The aim of the present study was to validate a study questionnaire by comparing children's use of special diets as reported by parents with patient records at the hospital.
A population-based cohort with genetic susceptibility to type 1 diabetes (15% of those screened) was recruited in the Tampere area between 1997 and 2001, and followed for development of food allergy for 3 years. Food allergies and other special diets were queried at the age of 3 years with a structured questionnaire. The hospital records of the children, whose parents had reported an elimination diet of the child, were studied to validate the parental reports of food allergies. The hospital database was also checked for the respective diagnosis codes to estimate underreporting.
Altogether, 1122 parents returned the questionnaire at the study center visit when the child was 3 years old. Food allergy was reported by 15.0% of the parents. In 10.6% of the children food allergy had been diagnosed or confirmed at the hospital. Hospital-confirmed food allergy was unreported in 0.9% of the cases. The measure of agreement between reported and hospital-confirmed food allergies, using crosstabulation with Cohen's Kappa, was within 0.71-0.88 for cow's milk allergy, 0.74-0.82 for cereal allergy and 0.66-0.86 for any reported food allergy.
We found that the validity of the questionnaire obtaining information on food allergies of infants and young children was good to excellent based on a comparison between parental reports and information obtained from patient records.
In Finland the world-record for the highest incidence of type 1 diabetes has risen steeply over the past decades. However, after 2006 the incidence rate has plateaued. We showed earlier, that despite the strong genetic disease component, environmental factors are driving the increasing disease incidence.
Since vitamin D intake has increased considerably in the country since 2003, we analyzed how serum 25-hydroxyvitamin D (25[OH]D) concentration changed over time in healthy children, and the timely relation of these changes to disease incidence.
The birth cohort of the Finnish Type 1 Diabetes Prediction and Prevention project was used to explore longitudinal changes in serum 25-hydroxyvitamin concentrations. The sampling period was limited to children born from 1994 to 2004, with serum samples collected during 1998-2006 in the Turku area, Southwest Finland (60 ?N).
25(OH)D concentrations were measured every 3-6 months from birth, ages ranging from 0.3 to 12.2 years (387 subjects, 5334 measurements).
Serum 25(OH)D concentrations were markedly lower before 2003 than after (69.3 ? 1.0 nmol/L vs 84.9 ? 1.3 nmol/L, respectively, P
Human bocavirus 1 (HBoV1) DNA is frequently detected in the upper airways of young children with respiratory symptoms. Because of its persistence and frequent co-detection with other viruses, however, its etiologic role has remained controversial. During 2009-2011, using HBoV1 IgM, IgG, and IgG-avidity enzyme immunoassays and quantitative PCR, we examined 1,952 serum samples collected consecutively at 3- to 6-month intervals from 109 constitutionally healthy children from infancy to early adolescence. Primary HBoV1 infection, as indicated by seroconversion, appeared in 102 (94%) of 109 children at a mean age of 2.3 years; the remaining 7 children were IgG antibody positive from birth. Subsequent secondary infections or IgG antibody increases were evident in 38 children and IgG reversions in 10. Comparison of the seroconversion interval with the next sampling interval for clinical events indicated that HBoV1 primary infection, but not secondary immune response, was significantly associated with acute otitis media and respiratory illness.
Human leukocyte antigen (HLA) genotypes associated with increased risk for type 1 diabetes mellitus (T1D) have been reported to be associated with increased birth weight. We set out to investigate the association between HLA haplotypes conferring risk for T1D and birth weight and search for possible differences in the strength of these associations among populations with contrasting incidence of T1D.
As a part of the EU-funded DIABIMMUNE study, genotyping for the HLA haplotypes associated with T1D was performed in 8369 newborn infants from Estonia, Finland and Russian Karelia. Infants born before 35 gestational weeks, from mothers with diabetes, and multiple pregnancies were excluded. Relative birth weight, expressed in standard deviation scores, was estimated for each gestational week, sex and country. The standard deviation scores were calculated internally using the actual population studied. According to their HLA haplotypes, participants were divided into risk groups, and the distribution of birth weight between quartiles was analysed.
We did not find any direct association between various HLA risk-associated genotypes (HLA DR3-DQ2/DR4-DQ8, DR3-DQ2/X or DR4-DQ8/X) and birth weight. We observed a significant relationship between increased relative birth weight and the protective HLA-DR2-DQ6 and DR13-DQ6 haplotypes. This association was significant only when these haplotypes were found together with the DR4-DQ8 haplotype.
The previously reported association between HLA-risk haplotypes for T1D and an increased birth weight was not confirmed. This suggests that the mechanisms behind the association between high birth weight and risk for T1D may be not directly HLA related.
Fruit and vegetable intake has been associated with a reduced risk of many chronic diseases. These foods are the main dietary source of carotenoids. The aim of the present study was to evaluate the associations between dietary intake and serum concentrations of a- and ß-carotene in a sample of young Finnish children from the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention (DIPP) Study. The current analysis comprised 3-day food records and serum samples from 207 children aged 1, 2 and 3 years. Spearman and partial correlations, as well as a cross-classification analyses, were used to assess the relationship between dietary intake and the corresponding biomarkers. Serum concentrations of a- and ß-carotene were significantly higher among the 1-year-old compared to the 3-year-old children. Dietary intakes of a- and ß-carotene correlated significantly with their respective serum concentrations in all age groups, the association being highest at the age of 1 year (a-carotene r = 0.48; p
In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility.
We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0.9-21.1 years). Islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD (GADA) and islet antigen 2 (IA-2A) were assessed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years of autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers, including 25 non-HLA SNPs predisposing to type 1 diabetes.
Altogether, 1550 children (21%) tested positive for at least one diabetes-associated autoantibody in at least two samples, and 248 (16%) of seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n = 42, 17%) and 5.4 years in slower progressors. Rapid progression was observed both among young (7 years), resulting in a double-peak distribution of seroconversion age. Compared with slower progressors, rapid progressors had a higher frequency of positivity for multiple (=2) autoantibodies and had higher titres of ICA, IAA and IA-2A at seroconversion, and there was a higher prevalence of the secretor genotype in the FUT2 gene among those carrying the high-risk HLA genotype. Compared with autoantibody-positive non-progressors, rapid progressors were younger, were more likely to carry the high-risk HLA genotype and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA and IA-2A positivity and multipositivity, and had higher titres of all four autoantibodies at seroconversion.
At seroconversion, individuals with rapid progression to type 1 diabetes were characterised by a younger age, higher autoantibody titres, positivity for multiple autoantibodies and higher prevalence of a FUT2 SNP. The double-peak profile for seroconversion age among the rapid progressors demonstrates for the first time that rapid progression may take place not only in young children but also in children in early puberty. Rapid progressors might benefit from careful clinical follow-up and early preventive measures.
Cites: Lancet. 1974 Nov 30;2(7892):1279-83 PMID 4139522
To characterize the humoral immune response to islet antigen 2 (IA-2) in patients with newly diagnosed type 1 diabetes (T1D), we compared the profile of epitope- and isotype-specific IA-2 antibodies (IA-2A) between children with a humoral immune response restricted to IA-2 and children with a broad response including insulin autoantibodies (IAA) and antibodies to glutamic acid decarboxylase (GADA) in addition to IA-2A.
The study subjects (n=100) were derived from a consecutive series of 1108 patients from the Finnish Pediatric Diabetes Register (investigators listed in the Appendix). Islet cell antibodies, IAA, GADA, total IA-2A levels, IA-2/IA-2beta epitopes, and isotypes were measured, and human leukocyte antigen (HLA) genotypes were analyzed.
There were no significant differences between the two groups in the frequency or levels of epitope-specific IA-2A. Those with an IA-2-restrictive response tested positive more frequently for IgA-IA-2A (P=0.001), had higher titers of IgE-IA-2A (P=0.025), tested positive for more IA-2A isotypes than the broad responders (P=0.04), and carried the high-risk HLA-(DR4)-DQB1*0302 haplotype more frequently than those with a broad antibody response (P=0.019).
These data show that children with newly diagnosed T1D, who test positive only for IA-2A out of the three molecular antibodies predictive of T1D, have a broader IA-2-specific isotype response and stronger association with the high-risk HLA haplotype than those testing positive for all three molecular antibodies. This may be indicative of a different pathogenetic mechanism in those with their humoral immune response restricted to IA-2 at the time of diagnosis.
A declining first-phase insulin response (FPIR) is characteristic of the disease process leading to clinical type 1 diabetes. It is not known whether reduced FPIR depends on class II human leukocyte antigen (HLA) genotype, islet autoimmunity, or both.
To dissect the role of class II HLA DR-DQ genotypes and biochemical islet autoantibodies in the compromised FPIR.
A total of 438 children with defined HLA DR-DQ genotype in the prospective Finnish Type 1 Diabetes Prediction and Prevention Study were analyzed for FPIR in a total of 1149 intravenous glucose tolerance tests and were categorized by their HLA DR-DQ genotype and the number of biochemical islet autoantibodies at the time of the first FPIR. Age-adjusted hierarchical linear mixed models were used to analyze repeated measurements of FPIR.
The associations between class II HLA DR-DQ genotype, islet autoantibody status, and FPIR.
A strong association between the degree of risk conferred by HLA DR-DQ genotype and positivity for islet autoantibodies existed (P
Major advances have been made in the classification and genetics of monogenic diabetes in infancy.
The objective of the study was to characterize different forms of diabetes diagnosed during the first year of life.
Patients diagnosed with diabetes before the age of 1 year in 10 Finnish hospitals from 1980 to 2014 were included.
The study was conducted at Kuopio University Hospital and University of Eastern Finland.
Patients were identified through diagnosis-based searches from hospital registries including 93 children, of whom 64 participated.
DNA sample for sequencing, serum sample, and medical records interventions were included.
Incidence of diabetes during the first year of life, sequencing results, human leukocyte antigen (HLA) genotypes, and islet autoantibodies were measured.
The incidence of diabetes diagnosed during the first 12 months was 4.4/100 000/year. Three novel and 11 previously described mutations were found in 22 patients from 15 families in the KCNJ11, ABCC8, INS, GCK, FOXP, STAT3, and RFX6 genes. Positive islet autoantibodies were observed in 40.0% of the patients diagnosed during the first 0-6 months of life vs 70.8% of the patients diagnosed between ages of 7 to 12 months. A total of 85.7% of the patients carrying protective HLA genotypes were mutation-positive compared to 7.7% of the patients having high-risk genotypes (P = .001).
Mutations in the K-ATP channel and INS genes were the most common cause of early diagnosed monogenic diabetes. After 6 months of age, patients with diabetes had high HLA risk genotypes and islet autoantibodies, reflecting the autoimmune character of diabetes in that age group.