TY - JOUR AB - Objective: To design a dynamic prediction model for estimating the time of progression from a single glutamic acid decarboxylase autoantibody (GADA) to multiple islet autoantibodies and type 1 diabetes in children, exploring different longitudinally measured risk variables. Research Design and Methods: GADA-positive children (n = 379) participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study were followed for the appearance of additional autoantibodies against either insulin autoantibody (IAA), insulinoma-like 2 autoantibody (IA-2A), or zinc transporter 8 antibody (ZnT8A) and type 1 diabetes. A dynamic prediction model was designed, including trajectories of longitudinal risk variables, autoantibody titers, and metabolic variables (C-peptide, glucose, and HbA1c) together with time-invariant variables (gender, age at GADA positivity, and high-risk HLA genotypes). Results: Transition risk from GADA to multiple autoantibodies was increased by lower age (p < 0.001) and by increased GADA titers during follow-up (p < 0.001), and was less likely in children with HLA DQ2/X but not DQ2/8 (p=0.004). The transition risk from multiple autoantibodies without IA-2A to IA-2A positivity was associated with increased levels of 2 h glucose following oral glucose tolerance test (OGTT) (p < 0.001) and increased ZnT8A titers (p < 0.001). Increasing HbA1c (p < 0.001) and GADA titers (p < 0.001) were associated with an increased risk of transition from GADA only to type 1 diabetes; while increasing HbA1c (p < 0.001) was associated with the transition from multiple autoantibodies to type 1 diabetes. Risk of transition from multiple autoantibodies, including IA-2A to type 1 diabetes was also associated with 2 h glucose level (p < 0.001). Conclusion: The dynamic prediction model presented an individual time-specific risk of transition from a single GADA to multiple autoantibodies and type 1 diabetes. AU - You, L.* AU - Salami, F.* AU - Tamura, R.* AU - Törn, C.* AU - Vehik, K.* AU - Hagopian, W.A.* AU - Rewers, M.J.* AU - McIndoe, R.A.* AU - Toppari, J.* AU - Ziegler, A.-G. AU - Akolkar, B.* AU - Krischer, J.P.* AU - Lernmark, Å.* C1 - 75628 C2 - 58182 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Predictors of transitions from GADA as the initial autoantibody to multiple autoantibodies of type 1 diabetes in children at risk by a dynamic prediction model. JO - Pediatr. Diabetes VL - 2025 IS - 1 PB - Wiley PY - 2025 SN - 1399-543X ER - TY - JOUR AB - BACKGROUND/OBJECTIVE: Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. RESEARCH DESIGN AND METHODS: Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. RESULTS: We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042. CONCLUSIONS: This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA. AU - Aronsson, C.A.* AU - Tamura, R.* AU - Vehik, K.* AU - Uusitalo, U.* AU - Yang, J.* AU - Haller, M.J.* AU - Toppari, J.* AU - Hagopian, W.* AU - McIndoe, R.A.* AU - Rewers, M.J.* AU - Ziegler, A.-G. AU - Akolkar, B.* AU - Krischer, J.P.* AU - Norris, J.M.* AU - Virtanen, S.M.* AU - Larsson, H.E.* C1 - 67963 C2 - 54441 CY - Adam House, 3rd Fl, 1 Fitzroy Sq, London, Wit 5he, England TI - Dietary intake and body mass index influence the risk of islet autoimmunity in genetically at-risk children: A mediation analysis using the TEDDY Cohort. JO - Pediatr. Diabetes VL - 2023 PB - Wiley-hindawi PY - 2023 SN - 1399-543X ER - TY - JOUR AU - Besser, R.E.J.* AU - Bell, K.J.* AU - Couper, J.J.* AU - Ziegler, A.-G. AU - Wherrett, D.K.* AU - Knip, M.* AU - Speake, C.* AU - Casteels, K.* AU - Driscoll, K.A.* AU - Jacobsen, L.* AU - Craig, M.E.* AU - Haller, M.J.* C1 - 66375 C2 - 53157 SP - 1175-1187 TI - ISPAD clinical practice consensus guidelines 2022: Stages of type 1 diabetes in children and adolescents. JO - Pediatr. Diabetes VL - 23 IS - 8 PY - 2022 SN - 1399-543X ER - TY - JOUR AB - This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents. Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study. Parents were asked to complete this questionnaire after they were told their child had an increased risk for T1D (Freder1k-study) and at several timepoints during an intervention study (POInT-study), where oral insulin was administered daily. Data were collected from 2595 parents of 1371 children across five countries. Disease-specific anxiety was found in a larger group of parents (47.2%) during the intervention study. Panic-related anxiety symptoms were reported by only 4.9% after hearing about their child having an increased risk. Symptoms of depression were limited to 19.4% of the parents at the result-communication visit and declined over time during the intervention study. Mothers and parents with a first-degree relative (FDR) with T1D reported more symptoms of depression and disease-specific anxiety (p < 0.001) than fathers and parents without a FDR. Overall, symptoms of depression and panic-related anxiety are comparable with the German general population. However, high levels of disease-specific anxiety were found during the intervention study, which should be kept in mind when considering population-based screening. As certain subgroups are more prone, it will be important to continue psychological screening and, when necessary, to provide support by an experienced, multidisciplinary team. This article is protected by copyright. All rights reserved. AU - Houben, J.* AU - Janssens, M.* AU - Winkler, C. AU - Besser, R.E.J.* AU - Dzygalo, K.* AU - Fehn, A. AU - Hommel, A.* AU - Lange, K.* AU - Elding Larsson, H.* AU - Lundgren, M.* AU - Roloff, F.* AU - Snape, M.* AU - Szypowska, A.* AU - Weiss, A. AU - Zapardiel-Gonzalo, J. AU - Ziegler, A.-G. AU - Casteels, K.* C1 - 66620 C2 - 53249 CY - Adam House, 3rd Fl, 1 Fitzroy Sq, London, Wit 5he, England SP - 1707-1716 TI - The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study. JO - Pediatr. Diabetes VL - 23 IS - 8 PB - Wiley-hindawi PY - 2022 SN - 1399-543X ER - TY - JOUR AB - BACKGROUND/OBJECTIVES: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age. RESULTS: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p<0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75,0.97], p=0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82,0.99], p=0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p<0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p<0.001). CONCLUSION: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies. This article is protected by copyright. All rights reserved. AU - Salami, F.* AU - Tamura, R.* AU - You, L.* AU - Lernmark, Å.* AU - Elding Larsson, H.* AU - Lundgren, M.* AU - Krischer, J.* AU - Ziegler, A.-G. AU - Toppari, J.* AU - Veijola, R.* AU - Rewers, M.* AU - Haller, M.J.* AU - Hagopian, W.* AU - Akolkar, B.* AU - Törn, C.* C1 - 66154 C2 - 53093 CY - Adam House, 3rd Fl, 1 Fitzroy Sq, London, Wit 5he, England SP - 1586-1593 TI - HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children. JO - Pediatr. Diabetes VL - 23 IS - 8 PB - Wiley-hindawi PY - 2022 SN - 1399-543X ER - TY - JOUR AB - OBJECTIVE: Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. METHODS: Autoantibodies to the parietal cell autoantigen, H+ /K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. RESULTS: The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6-9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CO, 1.3 - 2.8; P = .0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9 - 5.9; P < .0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5-5.5; P < .0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6 - 26.7) by age 20 years and was 47.3% (95% CI, 41.3-53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/DR4-DQ8, or DR3/DR3 genotype (P < .0001 vs other genotypes). CONCLUSIONS: Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs. AU - Zielmann, M.L.* AU - Jolink, M. AU - Winkler, C. AU - Eugster, A.* AU - Müller, D.* AU - Scholz, M. AU - Ziegler, A.-G. AU - Bonifacio, E. C1 - 64997 C2 - 52605 SP - 714-720 TI - Autoantibodies against ATP4A are a feature of the abundant autoimmunity that develops in first-degree relatives of patients with type 1 diabetes. JO - Pediatr. Diabetes VL - 23 IS - 6 PY - 2022 SN - 1399-543X ER - TY - JOUR AB - OBJECTIVE: We examined parental diabetes monitoring behaviors in a cohort of children at increased genetic risk for type 1 diabetes. We hypothesized that being informed of a positive islet autoantibody (IA) would increase monitoring behaviors. METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study follows 8676 children with high-risk HLA-DQ genotypes from birth to age 15, including general population children (GP) and those with a first-degree relative (FDR) with diabetes. Data on parental monitoring behaviors were solicited yearly. Serum samples were tested for IA and parents were informed of child results. We examined parental monitoring behaviors during the first 7 years of TEDDY. RESULTS: In IA- children, the most common monitoring behavior was participating in TEDDY study tasks; up to 49.8% and 44.2% of mothers and fathers, respectively, reported this. Among FDRs, 7-10% reported watching for diabetes symptoms and 7-9% reported monitoring the child's glucose, for mothers and fathers, respectively. After IA+ notification, all monitoring behaviors significantly increased in GP parents; only glucose monitoring increased in FDR parents and these behaviors continued for up to 4 years. FDR status, accurate diabetes risk perception, and anxiety were associated with glucose monitoring in IA+ and IA- cohorts. CONCLUSIONS: Many parents view TEDDY participation as a way to monitor for type 1 diabetes, a benefit of enrollment in a longitudinal study with no prevention offered. IA+ notification increases short- and long-term monitoring behaviors. For IA- and IA+ children, FDR parents engage in glucose monitoring, even when not instructed to do so. AU - Smith, L.B.* AU - Lynch, K.F.* AU - Driscoll, K.A.* AU - Johnson, S.B.* AU - TEDDY Study Group (Wendel, L. AU - Winkler, C. AU - Ziegler, A.-G. AU - Hummel, S.) C1 - 61551 C2 - 50340 SP - 717-728 TI - Parental monitoring for type 1 diabetes in genetically at-risk young children: The TEDDY study. JO - Pediatr. Diabetes VL - 22 IS - 5 PY - 2021 SN - 1399-543X ER - TY - JOUR AB - Objective The capacity to precisely predict progression to type 1 diabetes (T1D) in young children over a short time span is an unmet need. We sought to develop a risk algorithm to predict progression in children with high-risk human leukocyte antigen (HLA) genes followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods Logistic regression and 4-fold cross-validation examined 38 candidate predictors of risk from clinical, immunologic, metabolic, and genetic data. TEDDY subjects with at least one persistent, confirmed autoantibody at age 3 were analyzed with progression to T1D by age 6 serving as the primary endpoint. The logistic regression prediction model was compared to two non-statistical predictors, multiple autoantibody status, and presence of insulinoma-associated-2 autoantibodies (IA-2A). Results A total of 363 subjects had at least one autoantibody at age 3. Twenty-one percent of subjects developed T1D by age 6. Logistic regression modeling identified 5 significant predictors - IA-2A status, hemoglobin A1c, body mass index Z-score, single-nucleotide polymorphism rs12708716_G, and a combination marker of autoantibody number plus fasting insulin level. The logistic model yielded a receiver operating characteristic area under the curve (AUC) of 0.80, higher than the two other predictors; however, the differences in AUC, sensitivity, and specificity were small across models. Conclusions This study highlights the application of precision medicine techniques to predict progression to diabetes over a 3-year window in TEDDY subjects. This multifaceted model provides preliminary improvement in prediction over simpler prediction tools. Additional tools are needed to maximize the predictive value of these approaches. AU - Jacobsen, L.M.* AU - Elding Larsson, H.* AU - Tamura, R.N.* AU - Vehik, K.* AU - Clasen, J.* AU - Sosenko, J.M.* AU - Hagopian, W.A.* AU - She, J.X.* AU - Steck, A.K.* AU - Rewers, M.* AU - Simell, O.* AU - Toppari, J.* AU - Veijola, R.* AU - Ziegler, A.-G. AU - Krischer, J.P.* AU - Akolkar, B.* AU - Haller, M.J.* AU - The Teddy Study Group* C1 - 55113 C2 - 46330 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 263-270 TI - Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children. JO - Pediatr. Diabetes VL - 20 IS - 3 PB - Wiley PY - 2019 SN - 1399-543X ER - TY - JOUR AB - Objective We investigated the association between maternal use of vitamin D and omega-3 fatty acids (n-3 FAs) supplements during pregnancy and risk of islet autoimmunity (IA) in the offspring. Methods The Environmental Determinants of Diabetes in the Young (TEDDY) Study is prospectively following 8676 children with increased genetic risk for type 1 diabetes in Finland, Germany, Sweden, and the United States. Blood samples were collected every 3 months between 3 and 48 months of age then every 6 months thereafter to determine persistent IA. Duration, frequency, and supplement dose during pregnancy were recalled by mothers at 3 to 4 months postpartum. Cumulative intakes of supplemental vitamin D and n-3 FAs were analyzed as continuous or binary variables. We applied time-to-event analysis to study the association between maternal supplement use and IA, adjusting for country, human leukocyte antigen-DR-DQ genotype, family history of type 1 diabetes and sex. Secondary outcomes included insulin autoantibodies (IAA) or glutamic acid decarboxylase (GADA) as the first appearing autoantibody. Results As of February 2018, there were 747 (9.0%) children with IA. Vitamin D supplement intake during pregnancy (any vs none) was not associated with risk for IA (hazard ratio [HR] 1.11; 95% confidence interval [CI] 0.94, 1.31); neither was cumulative vitamin D supplement intake. Supplemental n-3 FA intake was similarly not associated with IA risk (HR: 1.19, 95% CI 0.98, 1.45). Similar lack of association was observed for either IAA or GADA as the first appearing autoantibody. Conclusions The TEDDY cohort showed no evidence of benefit regarding IA risk for vitamin D or n-3 FA supplementation during pregnancy. AU - Silvis, K.* AU - Aronsson, C.A.* AU - Liu, X.* AU - Uusitalo, U.* AU - Yang, J.* AU - Tamura, R.* AU - Lernmark, A.* AU - Rewers, M.* AU - Hagopian, W.* AU - She, J.X.* AU - Simell, O.* AU - Toppari, J.* AU - Ziegler, A.-G. AU - Akolkar, B.* AU - Krischer, J.* AU - Virtanen, S.M.* AU - Norris, J.M.* AU - Teddy Study Group* C1 - 54708 C2 - 45775 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 86-92 TI - Maternal dietary supplement use and development of islet autoimmunity in the offspring: TEDDY study. JO - Pediatr. Diabetes VL - 20 IS - 1 PB - Wiley PY - 2019 SN - 1399-543X ER - TY - JOUR AB - Primary prevention of type 1 diabetes (T1D) requires intervention in genetically at-risk infants. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD-02, that identifies infants with a genetic high risk of T1D, enrolls these into primary prevention trials, and follows the children for beta-cell autoantibodies and diabetes. Genetic testing is offered either at delivery, together with the regular newborn testing, or at a newborn health care visits before the age of 5 months in regions of Germany (Bavaria, Saxony, Lower Saxony), UK (Oxford), Poland (Warsaw), Belgium (Leuven), and Sweden (Region Skane). Seven clinical centers will screen around 330 000 infants. Using a genetic score based on 46 T1D susceptibility single-nucleotide polymorphisms (SNPs) or three SNPS and a first-degree family history for T1D, infants with a high (>10%) genetic risk for developing multiple beta-cell autoantibodies by the age of 6 years are identified. Screening from October 2017 to December 2018 was performed in 50 669 infants. The prevalence of high genetic risk for T1D in these infants was 1.1%. Infants with high genetic risk for T1D are followed up and offered to participate in a randomized controlled trial aiming to prevent beta-cell autoimmunity and T1D by tolerance induction with oral insulin. The GPPAD-02 study provides a unique path to primary prevention of beta-cell autoimmunity in the general population. The eventual benefit to the community, if successful, will be a reduction in the number of children developing beta-cell autoimmunity and T1D. AU - Winkler, C. AU - Haupt, F. AU - Heigermoser, M. AU - Zapardiel-Gonzalo, J. AU - Ohli, J. AU - Faure, T. AU - Kalideri, E. AU - Hommel, A.* AU - Delivani, P.* AU - Berner, R.* AU - Kordonouri, O.* AU - Roloff, F.* AU - von dem Berge, T.* AU - Lange, K.* AU - Oltarzewski, M.* AU - Glab, R.* AU - Szypowska, A.* AU - Snape, M.D.* AU - Vatish, M.* AU - Todd, J.A.* AU - Larsson, H.E.* AU - Ramelius, A.* AU - Kördel, J.* AU - Casteels, K.* AU - Paulus, J.* AU - Ziegler, A.-G. AU - Bonifacio, E.* C1 - 56327 C2 - 47004 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 720-727 TI - Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials-GPPAD-02 study design and first results. JO - Pediatr. Diabetes VL - 20 IS - 6 PB - Wiley PY - 2019 SN - 1399-543X ER - TY - JOUR AB - Individuals with a first degree relative with type 1 diabetes have an approximately 15-fold increased relative life time risk of type 1 diabetes . However at least 85% of children who develop type 1 diabetes do not have a family history of type 1 diabetes. AU - Couper, J.J.* AU - Haller, M.J.* AU - Greenbaum, C.J.* AU - Ziegler, A.-G. AU - Wherrett, D.K.* AU - Knip, M.* AU - Craig, M.E.* C1 - 54017 C2 - 45204 SP - 20-27 TI - ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents. JO - Pediatr. Diabetes VL - 19 PY - 2018 SN - 1399-543X ER - TY - JOUR AB - Background: Genetic predisposition for type 1 diabetes (T1D) is largely determined by human leukocyte antigen (HLA) genes; however, over 50 other genetic regions confer susceptibility. We evaluated a previously reported 10-factor weighted model derived from the Type 1 Diabetes Genetics Consortium to predict the development of diabetes in the Diabetes Autoimmunity Study in the Young (DAISY) prospective cohort. Performance of the model, derived from individuals with first-degree relatives (FDR) with T1D, was evaluated in DAISY general population (GP) participants as well as FDR subjects. Methods: The 10-factor weighted risk model (HLA, PTPN22, INS, IL2RA, ERBB3, ORMDL3, BACH2, IL27, GLIS3, RNLS), 3-factor model (HLA, PTPN22, INS), and HLA alone were compared for the prediction of diabetes in children with complete SNP data (n = 1941). Results: Stratification by risk score significantly predicted progression to diabetes by Kaplan-Meier analysis (GP: P=.00006; FDR: P=.0022). The 10-factor model performed better in discriminating diabetes outcome than HLA alone (GP, P=.03; FDR, P=.01). In GP, the restricted 3-factor model was superior to HLA (P=.03), but not different from the 10-factor model (P=.22). In contrast, for FDR the 3-factor model did not show improvement over HLA (P=.12) and performed worse than the 10-factor model (P=.02) Conclusions: We have shown a 10-factor risk model predicts development of diabetes in both GP and FDR children. While this model was superior to a minimal model in FDR, it did not confer improvement in GP. Differences in model performance in FDR vs GP children may lead to important insights into screening strategies specific to these groups. AU - Frohnert, B.I.* AU - Laimighofer, M. AU - Krumsiek, J. AU - Theis, F.J. AU - Winkler, C. AU - Norris, J.M.* AU - Ziegler, A.-G. AU - Rewers, M.J.* AU - Steck, A.K.* C1 - 51507 C2 - 43287 CY - Hoboken SP - 277-283 TI - Prediction of type 1 diabetes using a genetic risk model in the Diabetes Autoimmunity Study in the Young. JO - Pediatr. Diabetes VL - 19 IS - 2 PB - Wiley PY - 2018 SN - 1399-543X ER - TY - JOUR AB - Objective In children with presymptomatic type 1 diabetes, intermittent hyperglycemia and rising hemoglobin A1c levels are a known signal of progression toward insulin-dependency. Episodes of hypoglycemia, however, have also been reported in one published case. We investigated the prevalence of hypoglycemia and its association with disease progression in children with presymptomatic type 1 diabetes.Methods We compared the frequency of hypoglycemic fasting blood glucose levels (<60mg/dL) in 48 autoantibody negative and 167 multiple beta-cell autoantibody positive children aged 2 to 5years. We classified the autoantibody positive children into three categories based on their glucose levels in fasting state (hypoglycemic [<60mg/dL], normoglycemic [60-99mg/dL] or hyperglycemic [100mg/dL]). We then compared the glucose levels under challenge during oral glucose tolerance tests (OGTTs) between the three categories.Results In the autoantibody positive children, 5.1% of the fasting samples were hypoglycemic, while in the autoantibody negative children no hypoglycemia was observed. Hypoglycemia occurred more often in autoantibody positive children who had already entered stage 2 or stage 3 of type 1 diabetes than in stage 1 patients (P = 0.02). Children who had hypoglycemic compared to normoglycemic fasting blood glucose values had higher 120-minute blood glucose values under OGTT challenge, and a higher rate of pathological OGTTs (P = 0.04).Conclusions Fasting hypoglycemia seems to be an indicator of disease progression in presymptomatic type 1 diabetes and may therefore represent a novel marker for the identification of children who should be monitored more closely for progression toward insulin-dependent type 1 diabetes. AU - Heinrich, M. AU - Maison, N. AU - Achenbach, P. AU - Assfalg, R. AU - Braig, S.* AU - Böcker, D.* AU - Dunstheimer, D.* AU - Ermer, U.* AU - Gavazzeni, A.* AU - Gerstl, E.M.* AU - Hummel, S. AU - Kick, K. AU - Müller, H.* AU - Nellen-Hellmuth, N.* AU - Ockert, C.* AU - Sindichakis, M.* AU - Tretter, S.* AU - Warncke, K. AU - Ziegler, A.-G. AU - Beyerlein, A. C1 - 54130 C2 - 45359 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 1238-1242 TI - Fasting hypoglycemia is associated with disease progression in presymptomatic early stage type 1 diabetes. JO - Pediatr. Diabetes VL - 19 IS - 7 PB - Wiley PY - 2018 SN - 1399-543X ER - TY - JOUR AB - BACKGROUND: Diagnosis of type 1 diabetes often causes a negative psychological impact on families. We examined whether parents and children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study differ in their psychological adjustment to diabetes diagnosis compared to children diagnosed with diabetes in the community. METHODS: TEDDY follows 8676 children at genetic risk for type 1 diabetes from birth. Fifty-four TEDDY children diagnosed with diabetes and 54 age-matched community control children diagnosed with diabetes were enrolled. Participants were aged 3 to 10 years and study visits occurred at 3, 6, and 12 months postdiagnosis. Psychological measures included an adapted diabetes-specific State Anxiety Inventory, the Pediatric Quality of Life Inventory-Diabetes Module, and the Pediatric Inventory for Parents, which measures frequency and difficulty of parenting stress. RESULTS: A generalized estimating equation analysis based on a difference score between TEDDY children and community controls found no significant differences between TEDDY parents and community controls on parent diabetes-specific anxiety (P = .30). However, TEDDY children exhibited better diabetes-specific quality of life (P = .03) and TEDDY parents reported lower frequency (P = .004) and difficulty (P = .008) of parenting stress compared to community controls. CONCLUSIONS: Children diagnosed with at-risk for type 1 diabetes who have previously enrolled in research monitoring have improved diabetes quality of life and lower parenting stress postdiagnosis compared to children diagnosed in the community. Families in follow-up studies may be more prepared if their child is diagnosed with diabetes. AU - Smith, L.B.* AU - Liu, X.* AU - Johnson, S.B.* AU - Tamura, R.* AU - Elding Larsson, H.* AU - Ahmed, S.* AU - Veijola, R.* AU - Haller, M.J.* AU - Akolkar, B.* AU - Hagopian, W.A.* AU - Rewers, M.J.* AU - Krischer, J.* AU - Steck, A.K.* AU - TEDDY Study Group (Ziegler, A.-G. AU - Beyerlein, A. AU - Hummel, M. AU - Hummel, S. AU - Janz, N. AU - Knopff, A. AU - Peplow, C. AU - Roth, R. AU - Scholz, M. AU - Stock, J. AU - Strauss, E. AU - Warncke, K. AU - Wendel, L. AU - Winkler, C.) C1 - 55456 C2 - 46162 SP - 1025-1033 TI - Family adjustment to diabetes diagnosis in children: Can participation in a study on type 1 diabetes genetic risk be helpful? JO - Pediatr. Diabetes VL - 19 IS - 5 PY - 2018 SN - 1399-543X ER - TY - JOUR AB - ObjectiveTo explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community. Methods TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both participated in long-term follow up after diagnosis. Hemoglobin A1c (HbA1c) and mixed meal tolerance test were performed within 1month of diabetes onset, then at 3, 6, and 12months, and biannually thereafter. ResultsComparison of 43 TEDDY and 43 paired control children showed that TEDDY children often had no symptoms (58%) at diagnosis and none had diabetic ketoacidosis (DKA) compared with 98% with diabetes symptoms and 14% DKA in the controls (P<0.001 and P=0.03, respectively). At diagnosis, mean HbA1c was lower in TEDDY (6.8%, 51mmol/mol) than control (10.5%, 91mmol/mol) children (P<0.0001). TEDDY children had significantly higher area under the curve and peak C-peptide values than the community controls throughout the first year postdiagnosis. Total insulin dose and insulin dose-adjusted A1c were lower throughout the first year postdiagnosis for TEDDY compared with control children. ConclusionsHigher C-peptide levels in TEDDY vs community-diagnosed children persist for at least 12months following diabetes onset and appear to represent a shift in the disease process of about 6months. Symptom-free diagnosis, reduction of DKA, and the potential for immune intervention with increased baseline C-peptide may portend additional long-term benefits of early diagnosis. AU - Steck, A.K.* AU - Larsson, H.E.* AU - Liu, X.* AU - Veijola, R.* AU - Toppari, J.* AU - Hagopian, W.A.* AU - Haller, M.J.* AU - Ahmed, S.* AU - Akolkar, B.* AU - Lernmark, A.* AU - Rewers, M.J.* AU - Krischer, J.P.* AU - TEDDY Study Group (Ziegler, A.-G. AU - Beyerlein, A. AU - Bonifacio, E. AU - Hummel, M. AU - Hummel, S. AU - Foterek, K. AU - Janz, N. AU - Knopff, A. AU - Koletzko, S. AU - Peplow, C. AU - Roth, R. AU - Scholz, M. AU - Stock, J. AU - Strauss, E. AU - Warncke, K. AU - Wendel, L. AU - Winkler, C.) C1 - 52386 C2 - 43943 CY - Hoboken SP - 794-802 TI - Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls. JO - Pediatr. Diabetes VL - 18 IS - 8 PB - Wiley PY - 2017 SN - 1399-543X ER - TY - JOUR AB - BACKGROUND: Several studies indicate associations between early growth and type 1 diabetes (T1D). However, it remains an open question whether these findings can be translated to typical growth patterns associated with increased risk for T1D-associated islet autoimmunity. METHODS: We analyzed pooled data from 2236 children followed up in two large prospective German birth cohorts with a genetically increased risk for T1D including 18 564 measurements of height and weight, which were transformed to sex- and age-specific standard deviation scores (SDS). A total of 191 children developed any islet autoantibodies, 101 multiple islet autoantibodies. We applied a model-based clustering technique to derive typical height and body mass index (BMI) growth patterns, stratified for maternal T1D status. These patterns were used to predict islet autoimmunity in logistic regression models, adjusted for potential confounders. RESULTS: Growth patterns were not associated with islet autoimmunity in the whole dataset and in children of diabetic mothers, respectively. In children of non-diabetic mothers ,however, islet autoimmunity was associated with rapidly increasing BMI SDS values until the age of 3 yr [adjusted odds ratio (95% confidence interval): 2.02 (1.03, 3.73) for development of any islet autoantibodies) and with consistently above average height SDS values [odds ratio: 2.21 (1.15, 4.17)]. In contrast, a pattern of high height SDS values at birth followed by a decrease to average values after 3 yr was associated with a reduced rate of islet autoimmunity [odds ratio: 0.16 (0.01, 0.62)]. CONCLUSION: Early growth patterns may be associated with T1D-related islet autoimmunity risk in children of non-diabetic mothers. AU - Yassouridis, C.* AU - Leisch, F.* AU - Winkler, C. AU - Ziegler, A.-G. AU - Beyerlein, A. C1 - 48014 C2 - 39842 CY - Hoboken SP - 103-110 TI - Associations of growth patterns and islet autoimmunity in children with increased risk for type 1 diabetes: A functional analysis approach. JO - Pediatr. Diabetes VL - 18 IS - 2 PB - Wiley-blackwell PY - 2017 SN - 1399-543X ER - TY - JOUR AB - OBJECTIVE: Celiac disease (CD) is a common comorbidity of type 1 diabetes (T1D). Long-term consequences of CD are not completely understood, and adhering to a gluten-free diet is a burden for many patients. We investigated the effect of CD on vascular risk factors in a large cohort of T1D patients aged <20 yr. RESEARCH DESIGN AND METHODS: Within the longitudinal Diabetes Patienten Verlaufsdokumentation (DPV)-diabetes registry, data were analyzed from 59 909 < 20-yr-old T1D patients treated at 392 centers in Germany and Austria. A total of 974 patients with biopsy-proven celiac disease (BPCD) were compared with 28 398 patients without CD with respect to blood pressure (BP), lipids, glycohemoglobin (HbA1c ), body mass index (BMI), and reported smoking behavior. RESULTS: Patients with T1D and BPCD showed significantly lower high-density lipoprotein (HDL) cholesterol levels [median (interquartile range): 53.0 (43.0-62.6) mg/dL] than patients without CD [55.0 (45.0-66.0) mg/dL; p < 0.01; p < 0.001 after adjustment for confounding variables]. Systolic BP was lower in patients with CD [105.5 (100.0-112.5) mmHg] than in patients without CD [110.0 (102.0-117.0) mmHg; p < 0.0001; p < 0.001 after adjustment]. There were no significant differences regarding smoking behavior, BMI, or HbA1c . In a subgroup of 335 patients with BPCD, HDL cholesterol was measured 1 yr after diagnosis of CD:HDL increased by 8% (p < 0.01). CONCLUSION: Young people with T1D and CD have lower HDL cholesterol values than patients without CD. As low HDL cholesterol is associated with vascular risk, our findings support screening for CD and monitoring of HDL cholesterol in young people with T1D. AU - Warncke, K. AU - Liptay, S.* AU - Fröhlich-Reiterer, E.* AU - Scheuing, N.* AU - Schebek, M.* AU - Wolf, J.* AU - Rohrer, T.R.* AU - Meissner, T.* AU - Holl, R.W.* C1 - 43289 C2 - 36566 CY - Hoboken SP - 191-198 TI - Vascular risk factors in children, adolescents, and young adults with type 1 diabetes complicated by celiac disease: Results from the DPV initiative. JO - Pediatr. Diabetes VL - 17 IS - 3 PB - Wiley-blackwell PY - 2016 SN - 1399-543X ER - TY - JOUR AB - Background: Islet autoimmunity commonly develops early in infancy. We assessed whether specific parameters of early growth (including weight gain) were associated with the development of islet autoimmunity in children of type 1 diabetes patients, taking individual developmental patterns into account. Methods: Growth parameters were estimated in n=1011 children followed from birth in the prospective BABYDIAB and BABYDIET studies using longitudinal models. Cox proportional hazard models, adjusted for study, sex, gestational age, birth weight percentile, and maternal type 1 diabetes status, were calculated to assess hazard ratios (HR) for islet autoimmunity with corresponding 95% confidence intervals (95% CI) by 2 SD increases in growth parameters. In a subset of n=170 infants, we investigated whether the growth hormones insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) were in the causal pathway. Results: We found an early age at infant body mass index (BMI) peak to be associated with the development of islet autoimmunity [HR 0.60 (95% CI 0.41-0.87), per 2 SD increase in age]. Islet autoimmunity was also associated with BMI difference between infant BMI peak and childhood BMI rebound [HR 1.52 (95% CI 1.04-2.22)], but not after adjustment for age at infant BMI peak, and not with other parameters such as peak height and weight velocity during infancy. Serum concentrations of IGF-1 and IGFBP-3 at birth, 9 months, and 2yr, respectively, were not significantly different between children with and without later islet autoimmunity. Conclusions: Variations in early growth rate have subtle effects on the risk of islet autoimmunity with growth hormones unlikely to be in the causal pathway. AU - Beyerlein, A. AU - Thiering, E. AU - Pflueger, M. AU - Bidlingmaier, M.* AU - Stock, J. AU - Knopff, A. AU - Winkler, C. AU - Heinrich, J. AU - Ziegler, A.-G. C1 - 30696 C2 - 33824 SP - 534-542 TI - Early infant growth is associated with the risk of islet autoimmunity in genetically susceptible children. JO - Pediatr. Diabetes VL - 15 IS - 7 PY - 2014 SN - 1399-543X ER - TY - JOUR AU - Couper, J.J.* AU - Haller, M.J.* AU - Ziegler, A.-G. AU - Knip, M.* AU - Ludvigsson, J.* AU - Craig, M.E.* C1 - 32565 C2 - 35231 SP - 18-25 TI - Phases of type 1 diabetes in children and adolescents. JO - Pediatr. Diabetes VL - 15 PY - 2014 SN - 1399-543X ER - TY - JOUR AB - Objective: The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tolerance test (OGTT), and (iii) risk for early T1D is related to country, population, human leukocyte antigen (HLA)-genotypes and immunological markers. Methods: Autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3months of age in children with genetic risk. Symptoms and laboratory values at diagnosis were obtained and reviewed for ADA criteria. Results: The first 100 children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although young, 36% had no symptoms and ketoacidosis was rare (8%). An OGTT diagnosed 9/30 (30%) children above 3yr of age but only 4/70 (5.7%) below the age of 3yr. FDRs had higher cumulative incidence than children from the general population (p<0.0001). Appearance of all three autoantibodies at seroconversion was associated with the most rapid development of T1D (HR=4.52, p=0.014), followed by the combination of GADA and IAA (HR=2.82, p<0.0001). Conclusions: Close follow-up of children with genetic risk enables early detection of T1D. Risk factors for rapid development of diabetes in this young population were FDR status and initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA. AU - Elding Larsson, H.* AU - Vehik, K.* AU - Gesualdo, P.* AU - Akolkar, B.* AU - Hagopian, W.* AU - Krischer, J.P.* AU - Lernmark, A.* AU - Rewers, M.* AU - Simell, O.* AU - She, J.-X.* AU - Ziegler, A.-G. AU - Haller, M.J.* AU - TEDDY Study Group (Beyerlein, A. AU - Bonifacio, E. AU - Hummel, M. AU - Hummel, S. AU - Foterek, K. AU - Kersting, M. AU - Knopff, A. AU - Koletzko, S. AU - Peplow, C. AU - Roth, R. AU - Stock, J. AU - Strauss, E. AU - Warncke, K. AU - Winkler, C.) C1 - 30916 C2 - 34023 CY - Hoboken SP - 118-126 TI - Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. JO - Pediatr. Diabetes VL - 15 IS - 2 PB - Wiley-Blackwell PY - 2014 SN - 1399-543X ER - TY - JOUR AB - Background The application of autologous cord blood in children with type 1 diabetes has been found to be safe, but not to preserve beta-cell function in a previous study, which, however, had not included a control group. Objective To compare the changes of metabolic and immune function over time between cord blood infused children and natural controls. Subjects and methods Seven children with newly diagnosed type 1 diabetes underwent a single autologous cord blood infusion and 10 children were enrolled as natural controls in a non-randomized, controlled, open label intervention trial. Primary analyses were performed 1 year following cord blood infusion. Cases and controls were compared regarding metabolic [area under the curve (AUC) and peak C-peptide, insulin use, and HbA1c] and immune outcome (islet autoantibody titer and T-cell response), adjusted for age, gender, diabetes duration, and baseline levels. Results There were no significant adverse events related to the infusion. Metabolic and immune outcomes were not significantly different at 12 months follow-up between infused children and controls (e.g., adjusted p = 0.244 for AUC C-peptide, adjusted p = 0.820 for insulin use, adjusted p = 0.772 for peripheral regulatory T cells). Six-month change of AUC C-peptide correlated significantly with the number of infused CD34+ cells (r = 0.931, p = 0.002). Conclusions An autologous cord blood infusion does not change the natural course of metabolic and immune parameters after disease onset. However, the content of CD34+ cells in the stored blood sample might offer potential for improvement of future cell therapies. AU - Giannopoulou, E.Z. AU - Puff, R. AU - Beyerlein, A. AU - von Luettichau, I.* AU - Boerschmann, H.* AU - Schatz, D.* AU - Atkinson, M.* AU - Haller, M.J.* AU - Egger, D.* AU - Burdach, S.* AU - Ziegler, A.-G. C1 - 31085 C2 - 34239 CY - Hoboken SP - 100-109 TI - Effect of a single autologous cord blood infusion on beta-cell and immune function in children with new onset type 1 diabetes: A non-randomized, controlled trial. JO - Pediatr. Diabetes VL - 15 IS - 2 PB - Wiley-Blackwell PY - 2014 SN - 1399-543X ER - TY - JOUR AB - OBJECTIVE: To understand the association between life stress, postpartum depression (PD), maternal perception of her child's risk for type 1 diabetes (T1D) and a mother's anxiety about her child's T1D risk in mothers of genetically at risk children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: A short form of the state component (SAI) of the State-Trait Anxiety Inventory, negative life events (LE), the Edinburgh Postnatal Depression Scale (EPDS), and one question about the child's risk of developing T1D risk perceptions (RP) were given to mothers at the 6-month TEDDY clinic visit. The relationship between the four measures was modeled using multiple regressions. RESULTS: Controlling for sociodemographic factors, significant country differences in SAI, LE, EPDS, and RP emerged. LE - particularly interpersonal LE - had a strong association to maternal anxiety about the baby's risk of diabetes. Both evidence of PD and accurate risk perceptions (RPs) about the child's T1D risk were associated with increased maternal anxiety about the child's T1D risk. CONCLUSION: Heightened maternal anxiety in response to the news that a child is at increased risk for T1D is common. Mothers who have experienced recent negative LE, who experience PD and who accurately understand their child's risk may be particularly vulnerable to high levels of anxiety. The findings reported here need to be confirmed in future prospective studies. AU - Roth, R. AU - Lynch, K.* AU - Lernmark, B.* AU - Baxter, J.* AU - Simell, T.* AU - Smith, L.* AU - Swartling, U.* AU - Ziegler, A.-G. AU - Johnson, S.B.* AU - TEDDY Study Group (Beyerlein, A. AU - Bonifacio, E. AU - Hummel, M. AU - Hummel, S. AU - Foterek, K. AU - Kersting, M. AU - Knopff, A. AU - Koletzko, S. AU - Peplow, C. AU - Stock, J. AU - Strauss, E. AU - Warncke, K. AU - Winkler, C.) C1 - 31862 C2 - 34825 CY - Hoboken SP - 287-298 TI - Maternal anxiety about a child's diabetes risk in the TEDDY study: The potential role of life stress, postpartum depression, and risk perception. JO - Pediatr. Diabetes VL - 16 IS - 4 PB - Wiley-blackwell PY - 2014 SN - 1399-543X ER - TY - JOUR AB - Type 1 diabetes is preceded by the appearance of islet autoantibodies. Seroconversion to islet autoantibodies is greatest around 1 yr of age and is more frequent in children born to fathers with type 1 diabetes as compared to children born to mothers with type 1 diabetes. Here we asked whether changes in beta-cell function in the neonate and infant reflect variations in the incidence of islet autoantibody seroconversion. Insulin, proinsulin, and c-peptide concentrations were measured in sequential samples taken from birth to age 2 yr in 103 children who had a first degree relative with type 1 diabetes and who had been followed for islet autoantibody seroconversion. Serum insulin and proinsulin concentrations were highest at birth declining by age 3 months and stable thereafter until age 2 yr. C-peptide concentrations, proinsulin/insulin, and proinsulin/c-peptide ratios were stable from age 3 months. No differences were observed between children who developed islet autoantibodies and children who remained islet autoantibody negative. Children born to a mother with type 1 diabetes had higher birth concentrations of insulin (p = 0.005) and proinsulin (p = 0.014) as compared with children of non-diabetic mothers. Increased insulin concentrations in children of type 1 diabetes mothers persisted until age 6 months. In conclusion, we could not relate excursions in beta-cell hormones to autoantibody development, but suggest that the higher exposure to insulin and proinsulin in neonates born to mothers with type 1 diabetes may be linked to the relative protection against islet autoantibody seroconversion observed in these children. AU - Stumpp, C.* AU - Beyerlein, A. AU - Ziegler, A.-G. AU - Bonifacio, E.* C1 - 30801 C2 - 33881 SP - 528-533 TI - Neonatal and infant beta cell hormone concentrations in relation to type 1 diabetes risk. JO - Pediatr. Diabetes VL - 15 IS - 7 PY - 2014 SN - 1399-543X ER - TY - JOUR AB - AIM: To characterize the clinical and immunological features of HLA-typed youth with pediatric onset of type 2 diabetes mellitus (T2DM). METHOD: One hundred and seven patients with clinically diagnosed T2DM (aged ≤20 yr at diagnosis) were examined. DNA and serum, obtained after a median diabetes duration of 2.2 (Q1-Q3: 0.8-4.6) yr, were used for centralized HLA-typing and autoantibody (GADA, IA-2A, ZnT8A) measurements. RESULTS: 64.6% of patients were female and median age at diagnosis was 13.8 (Q1-Q3: 11.6-15.4) yr. Patients were obese [median body mass index-standard deviation score (BMI-SDS): 2.6 (2.0-3.1)], 88.0% had a family history of diabetes and 40.2% a migration background. Islet autoantibodies were detected in 16 (15.0%), among which 7 (6.5%) had multiple islet autoantibodies. Autoantibody positive patients had poorer metabolic control than autoantibody negative patients [glycosylated hemoglobin A1c (HbA1c): 8.1 (6.9-10.1) % vs. 6.6 (5.9-8.0) %; p = 0.033], while patients with HLA-DR genetic risk had higher BMI-SDS than those with HLA-DRXX [2.6 (2.4-3.7) vs. 2.4 (1.7-2.9); p = 0.007]. Metabolic syndrome (61.7%), microalbuminuria (13.4%), and retinopathy (3.9%) were diagnosed. Therapies used were lifestyle only (35.5%), oral anti-diabetics (OAD) only (43.3 %), insulin +  OAD (15.9%) and insulin only (5.6%). Patients with β-cell autoimmunity or HLA-DR genetic risk more frequently used insulin than confirmed T2DM patients (50.0 vs. 22.0%; p = 0.037) and less often had diabetic relatives (61.1 vs. 86.0%; p = 0.030). CONCLUSION: T2DM was confirmed in about 90% of patients while about 10% with β-cell autoimmunity or HLA-DR genetic risk likely had either T1.5DM or 'double diabetes' or an unknown diabetes type. AU - Awa, W.L.* AU - Boehm, B.O.* AU - Rosinger, S.* AU - Achenbach, P. AU - Ziegler, A.-G. AU - Krause, S. AU - Meissner, T.* AU - Wiegand, S.* AU - Reinehr, T.* AU - Kapellen, T.* AU - Karges, B.* AU - Eiermann, T.* AU - Schober, E.* AU - Holl, R.W.* C1 - 26084 C2 - 32061 SP - 562-574 TI - HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database. JO - Pediatr. Diabetes VL - 14 IS - 8 PB - Wiley-Blackwell PY - 2013 SN - 1399-543X ER - TY - JOUR AB - OBJECTIVE: To determine whether screening for islet autoantibodies in children prevents ketoacidosis and other metabolic complications at diabetes onset and improves the clinical course after diagnosis. SUBJECTS AND METHODS: The German BABYDIAB and the Munich Family Study follow children with a first-degree family history of type 1 diabetes for the development of islet autoantibodies and type 1 diabetes. The Diabetes Prospective Documentation (DPV) Initiative registers and collects information on pediatric patients with type 1 diabetes throughout Germany. Here, clinical characteristics at diabetes onset [ketoacidosis, mean hemoglobin A1c (HbA1c), and length of hospitalization] and the 5-yr clinical course (HbA1c and insulin dose) of screened and followed islet autoantibody-positive children (n = 101) and 49 883 non-screened children within the DPV registry were compared. RESULTS: At diabetes onset, children who were followed after screening and were positive for islet autoantibodies had lower HbA1c (8.6 vs. 11%, p < 0.001) and a lower prevalence of diabetic ketoacidosis (3.3 vs. 29.1%, p < 0.001). Screened children also had a shorter hospitalization period at onset (11.4 vs. 14.9 d, p = 0.005). Similar results were observed when the analysis was restricted to 759 non-screened DPV children with a first-degree family history of type 1 diabetes. No differences between screened and non-screened children were observed with respect to HbA1c and insulin dose during the first 5 yr after diagnosis. CONCLUSIONS: Screening for islet autoantibodies in children likely leads to earlier diabetes diagnosis resulting in less complications at diagnosis. However, no substantial benefit in the clinical outcome during the first 5 yr after diagnosis was observed. AU - Winkler, C. AU - Schober, E.* AU - Ziegler, A.-G. AU - Holl, R.W.* C1 - 23100 C2 - 30990 CY - Oxford SP - 308-313 TI - Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. JO - Pediatr. Diabetes VL - 13 IS - 4 PB - Wiley-Blackwell PY - 2012 SN - 1399-543X ER - TY - JOUR AB - Anette-Gabriele Ziegler, Franziska Meier-Stiegen, Christiane Winkler, Ezio Bonifacio, the TEENDIAB Study Group. Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty - TEENDIAB: study design. Type 1 diabetes (T1D) has a peak incidence in childhood and adolescence. The TEENDIAB study investigates the period of puberty and adolescence in the natural course of T1D development. Evidence suggests that the immune phenotype of children developing autoimmunity during puberty and adolescence differs from that in childhood. We hypothesize that these differences reflect heterogeneity in the genetic and environmental factors that influence the development of autoimmunity in puberty versus early infancy. TEENDIAB is an observational cohort study that enrols and follows 1500 children aged 8-12 and who have a first degree relative with T1D to test this hypothesis. Data collection and analyses will focus on determining the phenotype of islet autoimmunity, genotypes of T1D- and type 2 diabetes-associated genes, insulin resistance, and β-cell function, growth, obesity, and physical exercise. The findings of this study will increase the understanding of pathogenetic mechanisms behind the increasing diabetes incidence in youth and the impact of obesity on diabetes development in this age period. AU - TEENDIAB Study Group (Ziegler, A.-G. AU - Meier-Stiegen, F.* AU - Winkler, C. AU - Bonifacio, E.*) C1 - 4700 C2 - 28989 CY - Oxford SP - 438-443 TI - Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty - TEENDIAB: Study design. JO - Pediatr. Diabetes VL - 13 IS - 5 PB - Wiley-Blackwell PY - 2012 SN - 1399-543X ER -