Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes.

Objectives: Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were ≥ 10 times the upper limit of normal (10× ULN) predicted CD in T1D.

Methods: Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included.

Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial.

Aim: Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D).

Methods: 64 patients (T1D since <4 months, age 10-17.99, fasting sC-peptide ≥0.

Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY: Lessons From a 5-Year Pediatric Swedish National Cohort Study.

Objective: Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.

Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study.

Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

Patients And Methods: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

A longitudinal study of serum insulin-like growth factor-I levels over 6 years in a large cohort of children and adolescents with type 1 diabetes mellitus: A marker reflecting diabetic retinopathy.

Objective: To evaluate longitudinal serum insulin-like growth factor-I (IGF-I) in a large cohort of children and adolescents with type 1 diabetes in relation to hemoglobin A1c (HbA1c), age, diabetes duration, and body mass index (BMI), its association to height and retinopathy, and in comparison with healthy subject references.

Methods: A total of 2683 serum IGF-I values were obtained from 806 children and adolescents with T1DM, from annual blood samples for up to 6 consecutive years.

Results: In a multiple regression analysis IGF-I values were negatively correlated to HbA1c and diabetes duration, and positively correlated to BMI (P < .

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes.

Aim: It is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies.

Methods: Utilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D.

Results: In the training set, estimated risk scores were significantly different between patients and controls (P = 8.

Thyroid and Islet Autoantibodies Predict Autoimmune Thyroid Disease at Type 1 Diabetes Diagnosis.

Context: Screening of autoimmune thyroid disease in children with type 1 diabetes is important but varies between clinics.

Objective: To determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA-DQ at diagnosis of type 1 diabetes for autoimmune thyroid disease during follow-up.

Setting: Forty-three Swedish pediatric endocrinology units.

Self- and parent-reported executive problems in adolescents with type 1 diabetes are associated with poor metabolic control and low physical activity.

Background: Management of diabetes is demanding and requires efficient cognitive skills, especially in the domain of executive functioning. However, the impact of impaired executive functions on diabetes control has been studied to a limited extent. The aim of the study is to investigate the association between executive problems and diabetes control in adolescents with type 1 diabetes.

Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes.

The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next-generation sequencing (NGS) was used to determine all DRB alleles in consecutively diagnosed patients ages 1-18 years with islet autoantibody-positive type 1 diabetes (n = 970) and control subjects (n = 448). DRB3, DRB4, or DRB5 alleles were tested for an association with the risk of DRB1 for autoantibodies, type 1 diabetes, or both.

Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes? A retrospective case-control study.

Objective: To investigate long-term effects on glycaemic control, ketoacidosis, serious hypoglycaemic events, insulin requirements, and body mass index standard deviation scores (BMI-SDS) in children and adolescents with type 1 diabetes starting on continuous subcutaneous insulin infusion (CSII) compared with children and adolescents treated with multiple daily injections (MDI).

Methods: This retrospective case-control study compares 216 patients starting CSII with a control group on MDI (n = 215), matched for glycated hemoglobin (HbA1c), sex, and age during a 2-yr period. Variables collected were gender, age, HbA1c, insulin requirement, BMI, BMI-SDS, ketoacidosis, and serious hypoglycaemic events.

Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies.

Aims: The aim of this study was to explore whether islet cell antibodies (ICA) could be identified in children with newly onset diabetes mellitus but negative for autoantibodies against glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA), or any of the three variants with arginine (R), tryptophan (W), or glutamine (Q) at position 325 of the zinc transporter 8 (ZnT8A).

Methods: A population-based analysis of autoantibodies was performed from 1 May 2005 to 2 September 2010 in Swedish children newly diagnosed with diabetes. ICA was analyzed with an enzyme-linked immunosorbent assay and if positive, reanalyzed in the classical ICA immunofluorescence assay, in 341 samples among 3545 children who had been tested negative for all of GADA, IA-2A, IAA, or ZnT8A (R, W, Q).

High prevalence of celiac disease in Swedish children and adolescents with type 1 diabetes and the relation to the Swedish epidemic of celiac disease: a cohort study.

Aim: The aim was to determine the prevalence and clinical and temporal relationship of celiac disease (CD) in a population of Swedish children with type 1 diabetes mellitus (T1DM) before, during, and after the Swedish epidemic of CD (birth cohorts 1984-1996).

Methods: Retrospective chart review between 1995 and 2005 was conducted of 1151 children (0-18 years old, born 1981-2004) with T1DM.

Results: A prevalence of 9.

A multicenter observational safety study in Swedish children and adolescents using insulin detemir for the treatment of type 1 diabetes.

This 26-wk observational study in children and adolescents with type 1 diabetes (T1D) in Sweden investigated the safety and efficacy of insulin detemir (IDet) in newly diagnosed (ND) patients and those with established diabetes (ED) switching to IDet. A total of 159 patients initiated IDet as part of basal-bolus therapy, 59 in the ND stratum (mean age 9.7 yr) and 97 in the ED stratum (mean age 12.

Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study.

We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%).

Selective IgA deficiency in autoimmune diseases.

Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data.

Lower HbA1c after 1 year, in children with type 1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study.

Objective: Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH, although glargine has not been shown to improve HbA1c in randomized trials. Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking.

ZnT8 autoantibody titers in type 1 diabetes patients decline rapidly after clinical onset.

Autoantibodies to the islet-specific zinc transporter isoform 8 (ZnT8) are detected in the majority of type 1 diabetes patients prior to and at clinical diagnosis. The presence of ZnT8Ab after diagnosis has not been investigated. This study analyzed the autoantibody response to ZnT8 in regard to age at onset and disease duration.

Variations in incidence of type 1 diabetes in different municipalities of stockholm.

This article reports a test of the hypothesis that municipalities within the County of Stockholm have varying incidence rates of type 1 diabetes (T1D), suggesting a strong etiologic environmental component to the disease. The study group included T1D patients in the age group from birth to 18 years who were diagnosed each year from 20 municipalities in Stockholm County during the 1990-2003. Specific incidence rates by age, sex, and socioeconomic characteristics (income level, proportion of taxpayers, proportion of foreigners, population density and green cover) were estimated annually together with age standardization.

GAD treatment and insulin secretion in recent-onset type 1 diabetes.

Background: The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age.

Methods: We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.

Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations.

We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI. The potential of these markers to enhance the efficiency of type 1 diabetes risk screening was then evaluated by analyzing them in Finnish and Swedish populations. Blood spots on filter paper were analyzed using PCR followed by sequence-specific hybridization and time-resolved fluorometry reading.

Normalization of the IGF-IGFBP axis by sustained nightly insulinization in type 1 diabetes.

Objective: We sought to test the hypothesis that start of insulin glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGF binding proteins (IGFBPs) in adolescents with type 1 diabetes-changes that may support improvement of A1C.

Research Design And Methods: Twelve pubertal adolescents with type 1 diabetes and initially on NPH insulin were studied during 12 weeks of intensified treatment with glargine.

Results: Subnormal IGF-I SD scores on NPH (-1.

Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients.

Autoantibodies to the 65-kDa isoform of glutamate decarboxylase GAD65 (GAD65Ab) are strong candidates for a pathological role in Stiff-Person syndrome (SPS). We have analyzed the binding specificity of the GAD65Ab in serum and cerebrospinal fluid (CSF) of 12 patients with SPS by competitive displacement studies with GAD65-specific rFab-derived from a number of human and mouse mAbs specific for different determinants on the Ag. We demonstrate considerable differences in the epitope specificity when comparing paired serum and CSF samples, suggesting local stimulation of B cells in the CSF compartment of these patients.

Epitope analysis of GAD65Ab using fusion proteins and rFab.

The identification of disease-specific autoantibodies to the 65-kDa isoform of glutamate decarboxylase (GAD65Ab) epitopes in type 1 diabetes has been hampered by their conformational nature. Here, we compared two methods of GAD65Ab epitope analysis: GAD65/67 fusion proteins and competition assays using GAD65-specific recombinant fraction antigen binding (rFab). Sera from newly diagnosed type 1 diabetes patients (n=61) were studied using both approaches.

Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes.

Objective: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes.

Research Design And Methods: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years.