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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 (10x 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. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method., Funding Agencies|Barndiabetesfonden; Skane County Councils Research and Development Foundation

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. RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing. RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment. CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four isl, Funding Agencies|Swedish Child Diabetes Foundation; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK-063861]; National Institute for Health Research (U.K.)National Institute for Health Research (NIHR); Wellcome TrustWellcome Trust; Wellcome TrustWellcome Trust [098395/Z/12/Z]

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 < .001, P < .001, and P < .001, respectively, adjusted r2 = 0.102). Children and adolescents with T1DM had lower mean IGF‐I levels and reference interval limits compared to healthy subjects. In boys, mean (SD) IGF‐I SD score (SDS) levels were −1.04 (±1.3) calculated from the healthy reference. IGF‐I peaked at 15 years of age, similarly to healthy controls, but with markedly lower levels in late puberty. Girls were more affected at later stages of puberty but with a slightly less depressed overall mean IGF‐I SDS of −0.69 (±1.2). In a subgroup of 746 subjects with fundus photography, a negative correlation was seen between individual mean IGF‐I SDS and preproliferative retinopathy (P = .004, adjusted r2 = 0.021). In another subgroup of 84 adolescents, no correlation was seen between individual mean IGF‐I SDS and target height SDS or distance to target height SDS. Conclusion Poor metabolic control and diabetes duration impact negatively on serum IGF‐I levels. A low individual mean IGF‐I level was associated with progression of retinopathy independently of HbA1c, age, gender, and diabetes duration. Disease, sex and age related IGF‐I SDS may become clinical helpful as a supplement to HbA1c in predicting the long‐term outcome for children and adolescents with T1DM., Funding Agencies|Novo-Nordisk; Sanofi; Lilly

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). Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018). Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD., Funding Agencies|Swedish Child Diabetes Foundation (Barndiabetesfonden); Region Skane; Sigurd and Elsa Golje Foundation; Sallskapet Baravard; Stiftelsen Samariten; HKH Kronprinsessan Lovisas Forening for Barnasjukvard