Aims/hypothesis To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome.Methods Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA 1c was measured centrally.Electronic supplementary material The online version of this article

OBJECTIVE -To compare the clinical parameters, C-peptide levels, pattern of islet cellspecific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression.RESEARCH DESIGN AND METHODS -We evaluated the clinical parameters, Cpeptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population.RESULTS -There were no differences in the clinical parameters between LADA and adultonset type 1 diabetes. Patients with LADA had lower BMI (P Ͻ 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P ϭ 0.001), and triglycerides (P ϭ 0.001); higher HDL cholesterol levels (P Ͻ 0.0001); and lower prevalence of hypertension (P ϭ 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P ϭ 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P ϭ 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P ϭ 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups.CONCLUSIONS -Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.

Background Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. Objective To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. Methods This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out. Results Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47‐1.55), P < .0001) and the diabetes‐related expenditure per capita [odd ratio 1.55 (1.49‐1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001). Conclusions Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

In a cohort of diabetic children, silent celiac disease had no obvious effect on metabolic control but negatively influenced weight gain.

Administration of DiaPep277 seems safe and may have beneficial effects on C-peptide levels over time in some patients with T1D, but this finding was not accompanied by reduced HbA1c or insulin requirement. Studies with more patients and longer follow-up are needed to further study the effect of DiaPep277.

Aims/hypothesis The variants of transcription factor 7-like 2 (TCF7L2) gene have been proposed to be associated with latent autoimmune diabetes in adults (LADA). We sought to confirm the possible association in Europeans and to examine the interaction between one gene variant and clinical data. Methods The TCF7L2 rs7903146 C-to-T polymorphism was genotyped in 211 LADA, 1,297 type 2 diabetic, 545 type 1 diabetic and 1,497 control individuals from Hungary. A meta-analysis of our and previously published studies was performed to evaluate the size and the heterogeneity of the gene effect.Results The meta-analysis yielded a significant effect of TCF7L2 T allele (OR 1.28; p<0.0001) on LADA risk without heterogeneity among Europeans. The T allele conferred equally strong susceptibility to LADA and type 2 diabetes. In the Hungarian dataset, the T allele was associated with LADA and type 2 diabetes, but not with type 1 diabetes.T allele carriers had significantly lower BMI than patients with the CC genotype in the LADA and type 2 diabetes groups (p=0.0021 and p=0.0013, respectively). In both diseases, the diabetes risk was significantly higher in the non-overweight than in the overweight BMI category (p=0.0013 and p<0.0001, respectively); susceptibility to LADA was increased by 2.84-fold in non-overweight individuals compared with overweight ones. Conclusions/interpretation The meta-analysis demonstrates that TCF7L2 rs7903146 polymorphism is a populationindependent susceptibility locus for LADA in Europeans. The effect size is similar for LADA and type 2 diabetes. The gene effect on diabetes risk may be modulated by BMI, such that the lower the BMI, the higher the gene effect.

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen–conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow’s milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2–12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, −1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1–Q3, 3.1–8.9] vs 5.8 years [Q1–Q3, 2.6–9.1]; difference, 0.2 years [95% CI, −0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777

Objective: Recent data have indicated the significance of vitamin D receptor (VDR) polymorphisms in type 1 diabetes mellitus (T1DM). We have studied the association of five known restriction enzyme polymorphisms of the VDR gene in patients with T1DM. Design and Methods: One hundred and seven children with T1DM (T1DM for 5 years; age, 1-14 years; boys/girls, 57/50; body mass index, 17:0^2:3 kg=m 2 ; haemoglobin A Ic (HbA Ic ), 7:87^1:05) and 103 healthy subjects were enrolled. The VDR polymorphisms ApaI, BsmI, FokI, TaqI and Tru9I ('a', 'b', 'f ', 't' and 'u' alleles respectively) were investigated. Results: The 't' and 'T' alleles miss the Hardy -Weinberg equilibrium ðP , 0:01Þ in control and diabetic populations; we therefore excluded this polymorphism from further analysis. We did not find a difference in the allele prevalence in T1DM patients and controls of any of the five polymorphisms. However, when the 'b', 'a' and 'u' alleles were simultaneously compared in girls, there was a significantly higher prevalence in patients with diabetes compared with controls ('b' þ 'a' þ 'u' present/absent: healthy, 0/53; diabetic, 13/37; P , 0:005). In boys the prevalence of 'b' þ 'a' þ 'u' genotype was similar in T1DM and controls. Conclusions: The impact of the 't' allele cannot be investigated in this study population. Not a single VDR polymorphism increases the susceptibility to T1DM. The common presence of the 'b', 'a' and 'u' alleles greatly increases the probability of T1DM in girls.