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.
OBJECTIVE: We studied the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in children in Finland. RESEARCH DESIGN: AND METHODS: From 2002 to 2005, data on virtually all children
Animal models suggest that androgen receptor gene polymorphisms might affect disease predisposition in human immune-mediated diabetes. The aim of this study was to investigate the effect of the human androgen receptor gene exon 1 CAG repeat polymorphisms on type 1 diabetes (T1D) susceptibility.
A combined strategy of case-control and family-based approaches was used. Affected sibling pair families (n=120), nuclear families (n=645) and cohorts of sporadic cases (n=208) and controls (n=1381) were genotyped for androgen receptor gene exon 1 CAG repeat polymorphism. An automated fluorescence-based DNA fragment-sizing method was used.
The distribution of CAG repeat alleles did not differ significantly between patients and controls. However, short repeat alleles (7-14) were more prevalent among cases in girls compared with controls (8.77% vs 5.91%; P=0.03). Long repeat alleles (19-28) were less frequent among HLA DR3-positive diseased boys than in DR3-positive control boys (32.6% vs 40.6%; P=0.011). The differences were not significant after adjustment for multiple comparisons. Transmission of CAG repeat alleles was not different from expected in the total material. However, transmissions to girls deviated from the expected value significantly (extended transmission disequilibrium test (ETDT) 37.82; P=0.0016). A decreased transmission of the alleles with 13, 20 and 26 repeats to girls was observed (T%0, P=0.046; T%25.5, P=0.0003, T%0, P=0.025).
The results do not support a common role for the androgen receptor gene exon 1 CAG repeat in T1D susceptibility; however, an effect of a disease variant in linkage disequilibrium could be detected.
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
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and inducible T-cell co-stimulator (ICOS) genes are important mediators of T-cell activation in autoimmune diseases. The aim of the current study was to assess the impact of CTLA-4 and ICOS genes on the susceptibility to type 1 diabetes among two populations with different disease incidence rates. Three single nucleotide polymorphisms (SNPs) within the CTLA-4 region (+49A/G, CT60A/G, CTBC217_1C/T) and two SNPs within the ICOS region (CTIC154_1 C/T, CTIC159 C/G) were genotyped in 955 control subjects and 574 diabetic patients of Estonian and Finnish descent. The current study confirms the involvement of the CTLA-4 but not the ICOS gene in susceptibility to type 1 diabetes. However, the risk alleles and the defined main risk haplotype were more common in the Finnish controls compared with the Estonians, indicating that this gene locus might also be one of the contributing factors to the higher disease incidence in Finland.
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
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.
Continuous glucose monitoring (CGM) parameters, self-monitored blood glucose (SMBG), HbA1c and oral glucose tolerance test (OGTT) were studied during preclinical type 1 diabetes mellitus.
Ten asymptomatic children with multiple (?2) islet autoantibodies (cases) and 10 age and sex-matched autoantibody-negative controls from the Type 1 Diabetes Prediction and Prevention (DIPP) Study were invited to 7-day CGM with Dexcom G4 Platinum Sensor. HbA1c and two daily SMBG values (morning and evening) were analyzed. Five-point OGTTs were performed and carbohydrate intake was assessed by food records. The matched pairs were compared with the paired sample t-test.
The cases showed higher mean values and higher variation in glucose levels during CGM compared to the controls. The time spent ?7.8mmol/l was 5.8% in the cases compared to 0.4% in the controls (p=0.040). Postprandial CGM values were similar except after the dinner (6.6mmol/l in cases vs. 6.1mmol/l in controls; p=0.023). When analyzing the SMBG values higher mean level, higher evening levels, as well as higher variation were observed in the cases when compared to the controls. HbA1c was significantly higher in the cases [5.7% (39mmol/mol) vs. 5.3% (34mmol/mol); p=0.045]. No differences were observed in glucose or C-peptide levels during OGTT. Daily carbohydrate intake was slightly higher in the cases (254.2g vs. 217.7g; p=0.034).
Glucose levels measured by CGM and SMBG are useful indicators of dysglycemia during preclinical type 1 diabetes mellitus. Increased evening glucose values seem to be common in children with preclinical type 1 diabetes mellitus.