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Background/objective: The aim of this study was to systematically assess the association of insulin-manipulation (intentional under- and/or overdosing of insulin), psychiatric comorbidity and diabetes complications., Methods: Two diagnostic interviews (Diabetes-Self-Management-Patient-Interview and Children's-Diagnostic-Interview for Psychiatric Disorders) were conducted with 241 patients (age 10-22) with type 1 diabetes (T1D) from 21 randomly selected Austrian diabetes care centers. Medical data was derived from medical records., Results: Psychiatric comorbidity was found in nearly half of the patients with insulin-manipulation (46.3%) compared to a rate of 17.5% in patients, adherent to the prescribed insulin therapy. Depression (18.3% vs 4.9%), specific phobia (21.1% vs 2.9%), social phobia (7.0% vs 0%), and eating disorders (12.7% vs 1.9%) were elevated in patients with insulin-manipulation. Females (37.7%) were more often diagnosed (P = 0.001) with psychiatric disorders than males (18.4%). In females, the percentage of psychiatric comorbidity significantly increased with the level of non-adherence to insulin therapy. Insulin-manipulation had an effect of +0.89% in HbA1c (P = <0.001) compared to patients adherent to insulin therapy, while there was no association of psychiatric comorbidity with metabolic control (HbA1c 8.16% vs 8.12% [65.68 vs 65.25 mmol/mol]). Ketoacidosis, severe hypoglycemia, and frequency of outpatient visits in a diabetes center were highest in patients with insulin-manipulation., Conclusions: This is the first study using a systematic approach to assess the prevalence of psychiatric disorders in patients who do or do not manipulate insulin in terms of intentional under- and/or overdosing. Internalizing psychiatric disorders were associated with insulin-manipulation, especially in female patients and insulin-manipulation was associated with deteriorated metabolic control and diabetes complications., (© 2018 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Background: The interaction between type 1 diabetes mellitus (T1DM) and attention deficit hyperactivity disorder (ADHD) in children and adolescents has been studied rarely. We aimed to analyse metabolic control in children and adolescents with both T1DM and ADHD compared to T1DM patients without ADHD., Patients and Methods: Auxological and treatment data from 56.722 paediatric patients (<20 years) with T1DM in the multicentre DPV (Diabetes Prospective Follow-up Initiative) registry were analysed. T1DM patients with comorbid ADHD were compared to T1DM patients without ADHD using multivariable mixed regression models adjusting for demographic confounders., Results: We identified 1.608 (2.83%) patients with ADHD, 80.8% were male. Patients with comorbid ADHD suffered twice as often from diabetic ketoacidosis compared to patients without ADHD [10.2; 9.7-10.8 vs [5.4; 5.3-5.4] (P < .0001). We also found significant differences in HbA1c [8.6% (7.3-9.4); 66.7 mmol/mol (56.3-79.4) vs 7.8% (7.0-9.0); 62.1 mmol/mol (53.2-74.7)], insulin dose/kg [0.9 IU/kg (0.7-1.1) vs 0.8 IU/kg (0.7-1.0)], body mass index-standard deviation score (BMI-SDS) [0.2 (-0.5 to 0.8) vs 0.3 (-0.3 to 0.9)], body weight-SDS [0.1 (-0.5 to 0.8) vs 0.3 (0.3 - 0.9)]; (all P < 0.0001), and systolic blood pressure after adjustment [mean: 116.3 vs 117.1 mm Hg)]; (P < 0.005)., Conclusion: Paediatric patients with ADHD and T1DM showed poor metabolic control compared to T1DM patients without ADHD. Closer cooperation between specialized paediatric diabetes teams and paediatric psychiatry/psychology seems to be necessary to improve diabetes care and metabolic control in this group of patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aims: Intrauterine exposure to hyperglycemia might impact the risk for future metabolic deteriorations. The aim was to characterize the association between different adipokines and neuropeptides and insulin resistance and BMI-SDS in children affected by diabetes during pregnancy., Methods: 76 children (mean age: 6 years, male:female = 36:40) born to mothers with gestational or pregestational diabetes and nondiabetic women were consecutively included for clinical assessments comprising anthropometrics and metabolic characterization [2-hour glucose tolerance test, leptin, peptide YY (PYY), neuropeptide Y (NPY), ghrelin, growth differentiation factor 15 (GDF-15), and adiponectin]., Results: The level of insulin resistance was associated with BMI-SDS (p < 0.001), leptin (p < 0.001), ghrelin (p = 0.002), age (p < 0.002) and negatively with GDF-15 (p = 0.005). BMI-SDS, leptin and GDF-15 were shown to have independent effects on insulin resistance by using a multiple regression model (additionally including age, and maternal diabetes status), whereas ghrelin lost significance (p = 0.345). No differences were present in adipokines and insulin resistance when children were evaluated by maternal glucometabolic status. However, we observed more strengthened associations between insulin resistance and covariates BMI-SDS and leptin in offspring of diabetic pregnancies., Conclusions: Young children with elevated BMI or leptin are affected by higher indices of insulin resistance, particularly those who were born to mothers with diabetes during pregnancy. The impact of this special risk constellation should be considered in future studies., (© 2016 S. Karger AG, Basel.)

Objective: The objective of this study was to explore metabolic risk factors and glycemic control in youth with type 1 diabetes treated with typical or atypical antipsychotics., Research Design and Methods: Data for 60,162 subjects with type 1 diabetes up to the age of 25 years registered in the nationwide German/Austrian Diabetes Survey were included in the analysis. BMI; HbA1c; treatment strategy; prevalence of hypertension, dyslipidemia, microalbuminuria, and retinopathy; frequency of hypoglycemia and diabetic ketoacidosis (DKA); and immigrant status among subjects treated with typical or atypical antipsychotics were compared with those without antipsychotic medication and analyzed by regression analysis., Results: A total of 291 subjects with type 1 diabetes (median diabetes duration 7.2 years) received antipsychotic medications (most commonly risperidone). Subjects treated with antipsychotics had a higher BMI (P = 0.004) and dyslipidemia was more frequent (P = 0.045) compared with subjects not receiving antipsychotic medication. Frequencies of severe hypoglycemia and DKA were significantly higher in subjects receiving antipsychotics (P < 0.001). The prevalences of hypertension, microalbuminuria, and retinopathy were not different. In subjects treated with typical antipsychotics, glycemic control did not differ compared with those who did not receive antipsychotic medications. By contrast, subjects treated with atypical antipsychotics had higher HbA1c levels (P = 0.022)., Conclusions: This analysis from a real-life survey demonstrated that subjects with antipsychotic medication had worse glycemic control and a higher rate of acute complications compared with those without antipsychotic medication. Health care teams caring for youth with type 1 diabetes taking antipsychotic medication need to know about these findings. We suggest monitoring metabolic risk factors as well as providing diabetes education about prevention of acute complications., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Importance: Exposing the oral mucosa to antigen may stimulate immune tolerance. It is unknown whether treatment with oral insulin can induce a tolerogenic immune response in children genetically susceptible to type 1 diabetes., Objective: To assess the immune responses and adverse events associated with orally administered insulin in autoantibody-negative, genetically at-risk children., Design, Setting, and Participants: The Pre-POINT study, a double-blind, placebo-controlled, dose-escalation, phase 1/2 clinical pilot study performed between 2009 and 2013 in Germany, Austria, the United States, and the United Kingdom and enrolling 25 islet autoantibody-negative children aged 2 to 7 years with a family history of type 1 diabetes and susceptible human leukocyte antigen class II genotypes. Follow-up was completed in August 2013., Interventions: Children were randomized to receive oral insulin (n = 15) or placebo (n = 10) once daily for 3 to 18 months. Nine children received insulin with dose escalations from 2.5 to 7.5 mg (n = 3), 2.5 to 22.5 mg (n = 3), or 7.5 to 67.5 mg (n = 3) after 6 months; 6 children only received doses of 22.5 mg (n = 3) or 67.5 mg (n = 3)., Main Outcomes and Measures: An immune response to insulin, measured as serum IgG and saliva IgA binding to insulin, and CD4+ T-cell proliferative responses to insulin., Results: Increases in IgG binding to insulin, saliva IgA binding to insulin, or CD4+ T-cell proliferative responses to insulin were observed in 2 of 10 (20% [95% CI, 0.1%-45%]) placebo-treated children and in 1 of 6 (16.7% [95% CI, 0.1%-46%]) children treated with 2.5 mg of insulin, 1 of 6 (16.7%[ 95% CI, 0.1%-46%]) treated with 7.5 mg, 2 of 6 (33.3% [95% CI, 0.1%-71%]) treated with 22.5 mg, and 5 of 6 (83.3% [ 95% CI, 53%-99.9%]) treated with 67.5 mg (P = .02). Insulin-responsive T cells displayed regulatory T-cell features after oral insulin treatment. No hypoglycemia, IgE responses to insulin, autoantibodies to glutamic acid decarboxylase or insulinoma-associated antigen 2, or diabetes were observed. Adverse events were reported in 12 insulin-treated children (67 events) and 10 placebo-treated children (35 events)., Conclusions and Relevance: In this pilot study of children at high risk for type 1 diabetes, daily oral administration of 67.5 mg of insulin, compared with placebo, resulted in an immune response without hypoglycemia. These findings support the need for a phase 3 trial to determine whether oral insulin can prevent islet autoimmunity and diabetes in such children., Trial Registration: isrctn.org Identifier: ISRCTN76104595.

Background: Despite a marked improvement in the overall prognosis of patients with type 1 diabetes mellitus (T1DM), cardiovascular morbidity/mortality is still increased. Since cellular and microvascular aberrations have been demonstrated already in children with T1DM, albeit a good glycemic control (CO), we hypothesized that early macrovascular changes can be detected by common carotid artery intima-media thickness (CCA-IMT)., Methods: We included 73 children/adolescents with T1DM (34 boys, 39 girls; mean age, 14.8 ± 2 years) and 243 sex- and age-matched healthy CO. In T1DM mean HbA1c was 7.9 ± 1.1 rel.%, and duration of disease 7.5 ± 3.1 years. High-resolution ultrasonography was used to assess CCA-IMT, defined as the mean of 24 measurements of the near and far wall on both right and left CCA., Results: CCA-IMT was not different in the total of children and adolescents with T1DM compared with CO (0.302 ± 0.057 vs. 0.301 ± 0.054 mm; p = 0.88). Analysis according to gender, however, revealed higher CCA-IMT values in girls than in boys in the diabetic cohort (0.315 ± 0.055 vs. 0.288 ± 0.058 mm; p = 0.047), whereas CCA-IMT was higher in boys than in girls in the CO group (0.321 ± 0.057 vs. 0.284 ± 0.045 mm; p < 0.001). Multiple stepwise backward regression showed that in the T1DM group only HbA1c remained significantly associated with CCA-IMT (Beta = - 0.307, p = 0.008). In CO, gender (Beta = - 0.302, p < 0.001), body mass index (Beta = 0.226, p < 0.001) and systolic blood pressure (Beta = 0.213, p < 0.001) were predictive of CCA-IMT., Conclusion: Our data suggest that in children/adolescents with T1DM the quality of metabolic CO (HbA1c) is the most important predictor of CCA-IMT and outweighs the effect of gender.

Objective: Recent literature suggests an association between type 1 diabetes (T1D) and depression. So far, most studies explored this link in adult populations, with few data being available on diabetes and depression from minors and young adults. This study aimed to look for associations between symptoms of depression/antidepressant treatment and metabolic outcomes of T1D., Methods: We conducted an observational study using the German diabetes database (Diabetes-Patienten-Verlaufsdokumentation--DPV) and searched for patients up to the age of 25 yr, with depressive symptoms and/or receiving antidepressant medication., Results: Of 53 986 T1D patients below the age of 25 yr, antidepressant medication and/or depressive symptoms were reported in 419 (0.78%). After adjustment for age, gender, diabetes duration and center heterogeneity, minors and young adults with depressive symptoms showed worse outcome parameters such as a higher rate of severe hypoglycemia (0.56 vs. 0.20/patient year, p = 0.005) and more episodes of diabetic ketoacidosis (0.20 vs. 0.07/patient year, p < 0.001). Hemoglobin A1c (HbA1c) was higher in the depression group (74.50 vs. 67.58 mmol/mol, p < 0.001) and young patients with T1D and depression showed longer duration of inpatient treatment (7.04 vs. 3.10 hospital days/patient year, p < 0.001) and more frequent admissions to hospital care (0.63 vs. 0.32/patient year, p < 0.001). Antidepressant medication was recorded in 52.3% of the depressed patients, with selective serotonin reuptake inhibitors (SSRIs) being the most widely described class of antidepressants (29.1%)., Conclusions: Our findings demonstrate an adverse treatment outcome for young patients with T1D and comorbid depressive symptoms underlining an urgent need for collaborative mental and somatic health care for patients with T1D and depression., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years., Methods and Findings: We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4 ± 3.8 y, range 1-20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19-1.37) to 1.05 (1.00-1.09) and from 1.39 (1.23-1.56) to 1.01 (0.93-1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6-1.7, p<0.001) and 1.9% (0.8-2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%-6.9% (RR 0.96 and 0.90 each year) and 7.0%-7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study., Conclusions: The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients. Please see later in the article for the Editors' Summary.

Objective: Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a side effect of intensified insulin therapy in type 1 diabetes (T1D). Paediatric studies are complicated by the age-dependency and gender-dependency of BMI, and also by a trend towards obesity in the general population. The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey., Design: Within the DPV database (Diabetespatienten Verlaufsdokumentation) a standardised, prospective, computer-based documentation programme, data of 53,108 patients with T1D, aged <20 years, were recorded in 248 centres. 12,774 patients (53% male, mean age 13.4±3.9, mean diabetes duration 4.7±3.0 years and mean age at diabetes onset 8.7±4.0 years) were included in this analysis. Population-based German reference data were used to calculate BMI-SDS and define overweight and obesity., Results: 12.5% of T1D patients were overweight and 2.8% were obese. Multiple longitudinal regression analysis revealed that female gender, low BMI at diabetes onset, intensified insulin therapy and higher insulin dose, as well as pubertal diabetes onset, long diabetes duration and onset in earlier calendar years among girls, were related to higher BMI-SDS increase during the course of diabetes (p<0.01; all)., Conclusions: Intensified insulin regimen is associated with weight gain during T1D treatment, in addition to demographic variables. Optimisation of diabetes management, especially in females, might limit weight gain in order to reduce overweight and obesity together with comorbidities among paediatric T1D patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims/hypothesis: The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old., Methods: Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (<7.5% [<58 mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared., Results: Insulin pump use was more frequent (74% vs 50%, p < 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p < 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p < 0.001) and injection users (p < 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c <7.5%: 56% vs 22%, p < 0.001; HbA1c <8.5%: 90% vs 66%, p < 0.001). The adjusted odds of having an HbA1c level <7.5% or <8.5% were 4.2 (p < 0.001) and 3.6 (p < 0.001) higher for the DPV than the T1DX, respectively. The frequency of SH did not differ between registries or by HbA1c, whereas the frequency of DKA was higher for the T1DX and greater in those with higher HbA1c levels., Conclusions/interpretation: DPV data indicate that an HbA1c of <7.5% can frequently be achieved in children with type 1 diabetes who are under 6 years old. An improved metabolic control of type 1 diabetes in young patients appears to decrease the risk of DKA without increasing SH. The greater frequency of suboptimal control in young patients in the T1DX compared with the DPV is not fully explained by a less frequent use of insulin pumps and may relate to the higher HbA1c targets that are recommended for this age group in the USA.

Objective: To facilitate child-specific and diabetes-related cholesterol control, we developed a monitoring algorithm derived from population-based reference values., Study Design: Low-density lipoprotein (LDL)-, non-high-density lipoprotein (HDL)-, and HDL cholesterol percentile values were calculated for children with type 1 diabetes (T1D) and their peers without T1D within algorithm-based categories of sex, age: 1-10 vs >10-<18 years, body mass index: <90th vs ≥90th percentile, and hemoglobin A1c <6%, 6%-<7.5%, 7.5%-9%, >9%. Analyses included 26 147 patients sampled from a German/Austrian population-based registry for T1D (Diabetes Documentation and Quality Management System) and 14 057 peers without diabetes participating in the national Health Interview and Examination Survey for Children and Adolescents in Germany., Results: Reference percentile values for cholesterol were derived as a diagnostic algorithm aimed at supporting long-term cholesterol control. Taking account of a patient's sex, age-group, weight-, and hemoglobin A1c-category, the flowcharts of the algorithm developed separately for LDL-, non-HDL-, and HDL cholesterol allow comparing his/her cholesterol levels with population-based reference percentile values of peers without T1D., Conclusions: The population-based algorithmic approach applied to LDL-, non-HDL-, and HDL cholesterol allows referencing children with T1D with regard to their peers without T1D and, if necessary, suggests corrections of glycemic control to optimize long-term cholesterol levels., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Hyperinsulinemic hypoglycemia (HH), characterized by unregulated insulin secretion, is an important cause of persistent and severe hypoglycemia. The biochemical picture of HH is hypoketotic hypo-fatty-acidemic hypoglycemia along with elevated serum insulin. Not infrequently, serum insulin might be undetectable in HH despite the presence of evidence of insulin action (suppressed ketogenesis and lipolysis). However, autonomous activity of the downstream insulin signaling pathway without the presence of the ligand (insulin) will give rise to the same clinical and biochemical picture, apart from undetectable serum insulin/C-peptide. AKT2, a serine/threonine protein kinase, is involved downstream to the insulin receptor in mediating the physiological effects of insulin., Aim: We describe the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypoglycemia., Patients and Methods: The proband presented with hemihypertrophy and symptomatic hypoglycemia. Investigations confirmed evidence of insulin action, despite absence of detectable serum insulin on multiple occasions. Molecular genetic testing for common causes of HH (ABCC8, KCNJ11, and GLUD1) was negative. Sequencing of AKT2 identified a de novo mosaic c.49G→A (p.E17K) mutation, consistent with the clinical and biochemical phenotype., Conclusions: This is the second report of an activating AKT2 mutation leading to hypoinsulinemic hypoketotic hypo-fatty-acidemic hypoglycemia. In patients presenting a clinical and biochemical picture of HH with undetectable serum insulin, consideration of autonomous activation of the downstream insulin signaling pathway should be made.

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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To analyze the effect of a community-based, poster-focused prevention program on the frequency of diabetic ketoacidosis (DKA) at diabetes onset in Austria., Study Design: All newly diagnosed patients with diabetes ≤ 15 years of age were registered prospectively by the Austrian Diabetes Incidence Study Group. Registered data included initial blood glucose, pH, and ketonuria. DKA was defined as pH < 7.3 and severe DKA as pH < 7.1. Data between 1989 and 2011 were available. In autumn, 2009, a community-based prevention program similar to the Parma Campaign, in which posters were dispensed broadly, was initiated. The frequency of DKA at the onset of diabetes in the years 2005-2009 and 2010-2011 was compared., Results: During the study period, 4038 children were registered. A total of 37.2% presented with DKA; 26% had a mild and 11.2% a severe form. The frequency of DKA was negatively associated with age at onset. In the years before the intervention program, 26% had mild DKA compared with 27% after the intervention (not significant). The prevalence of severe DKA in the years before the campaign was 12% compared with 9.5% thereafter (not significant). No significant change in the DKA rate at onset by the prevention program could be found when we compared age groups <5, 5 to <10, and 10 to <15 years, neither for mild nor for severe DKA., Conclusion: The frequency of DKA in children with newly diagnosed type 1 diabetes in Austria is high and did not change despite the efforts of a community-based information program., (Copyright © 2013. Published by Mosby, Inc.)

Objective: The risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control., Research Design and Methods: Children (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated., Results: EPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (β = -0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of -4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period., Conclusions: This is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise.

Objective: Down syndrome (DS) is associated with an increased risk of diabetes, particularly in young children. HLA-mediated risk is however decreased in children with DS and diabetes (DSD). We hypothesized that early-onset diabetes in children with DS is etiologically different from autoimmune diabetes., Research Design and Methods: Clinical and immunogenetic markers of autoimmune diabetes were studied in 136 individuals with DSD and compared with 194 age- and sex-matched individuals with type 1 diabetes, 222 with DS, and 671 healthy controls. HLA class II was analyzed by sequence-specific primed PCR. Islet autoantibodies were measured by radioimmunoassay., Results: Age at onset of diabetes was biphasic, with 22% of DS children diagnosed before 2 years of age, compared with only 4% in this age-group with type 1 diabetes in the general population (P < 0.0001). The frequency of the highest-risk type 1 diabetes-associated HLA genotype, DR3-DQ2/DR4-DQ8, was decreased in both early- and later-onset DSD compared with age-matched children with type 1 diabetes (P < 0.0001), although HLA DR3-DQ2 genotypes were increased (P = 0.004). Antibodies to GAD were observed in all five samples tested from children diagnosed at ≤2 years of age, and persistent islet autoantibodies were detected in 72% of DSD cases. Thyroid and celiac disease were diagnosed in 74 and 14%, respectively, of the DSD cohort., Conclusions: Early-onset diabetes in children with DS is unlikely to be etiologically different from autoimmune diabetes occurring in older DS children. Overall, these studies demonstrate more extreme autoimmunity in DSD typified by early-onset diabetes with multiple autoimmunity, persistent islet autoantibodies, and decreased HLA-mediated susceptibility.

Objective: Recent epidemiological evidence suggests that subclinical hypothyroidism (SCH), defined as elevated TSH concentrations with normal circulating levels of triiodothyronine (T3) and thyroxine (T4), is associated with dyslipidemia and cardiovascular disease in adult populations. As currently no data are available on the prevalence of SCH and its potential association with lipoprotein profile in children and adolescents with type 1 diabetes (T1DM), we investigated the prevalence of SCH and associated lipid levels in young diabetic patients., Design and Methods: Cross-sectional analysis of 22,747 children, adolescents, and young adults (age <25 years) with T1DM with normal T3 and T4 and either normal TSH (≥0.5 to <4.0 mIU/l, euthyroid group) or elevated TSH (≥4.0 to <25.0 mIU/l, SCH group) and simultaneous measurement of serum lipid and lipoprotein status., Results: The prevalence rate of SCH in the study population was 7.2%. Adjusted for age, gender, diabetes duration, current insulin dose, HbA1c, and BMI z-score, patients with SCH had significantly higher levels of total cholesterol (178.7 vs 175.3 mg/dl, P<0.001) and LDL-cholesterol (97.0 vs 93.7 mg/dl, P<0.001) compared with euthyroid patients., Conclusions: SCH is a common finding in children, adolescents, and young adults with T1DM. SCH is associated with increased levels of total cholesterol, and LDL-cholesterol adjusted for potential confounders. SCH-associated increases in lipid and lipoprotein levels may therefore add to an increased long-term cardiovascular risk in young patients with T1DM.

In contrast to adults Diabetes mellitus type 1 (DMT1) is the most frequent form of diabetes mellitus during childhood and adolescence (> 95 %). After diagnosis, the management of these DMT1-patients should take place in specialized paediatric centres, not in a primary care setting. The lifelong substitution of insulin is the cornerstone of therapy, the form of insulin-therapy should be adapted according to the age of the patient (conventional, intensified or pump therapy). Diabetes education is also an essential part in the management of diabetes patients and their families. The ISPAD (International Society for Paediatric and Adolescent Diabetes) recommends an HbA1c < 7.5 rel.%(IFCC < 58 mmol/mol) as good metabolic control, although it might be difficult to achieve this goal during different phases of life (e.g. toddlers or puberty). The aim of diabetes education and management is avoidance of acute and late diabetes related complications, as well as achievement of normal growth and psychosocial development and wellbeing.

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes mellitus, based on current evidence.

This position statement is based on the cur-rent evidence available on the safety and benefits of continous subcutaneous insulin pump therapy (CSII) in diabetes mellitus with an emphasis on the effects of CSII on glycemic control, hypoglycaemia rates, occur-ance of ketoacidosis, quality of life and the use of insu-lin pump therapy in pregnancy. The current article rep-resents the recommendations of the Austrian Diabetes Association for the clinical praxis of insulin pump treat-ment in children and adults.

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.

Objective: To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders., Research Design and Methods: Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies., Results: Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little., Conclusions: The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Mortality of cardiovascular diseases in patients with type 1 diabetes is increased 2- to 20-fold compared to non-diabetic individuals. In young adults with type 1 diabetes, cardiovascular events are more often the cause of premature death than nephropathy. The aim of this study was to evaluate the prevalence and extent of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria. In a cross sectional study data of children with type 1 diabetes <18 years of age treated at the Children's department of the University Hospitals of Vienna and Graz were collected. We recorded body mass index, waist circumference, blood pressure, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol according to age, sex, age at manifestation, diabetes duration, and insulin requirement. From 264 patients (49.4% male) complete data were available. Of all patients, 76.1% had one or more risk factors, 20.8% had two or more, 10.2% had three or more, and 4.9% had four or more risk factors. Insufficient glycemic control was the most frequent risk factor, present in 60.6% of our patients, followed by elevated triglycerides (22.7%) and increased body mass index (20.1%). Higher prevalence of risk factors was correlated with increasing age, diabetes duration, HbA1c, and insulin requirement. In conclusion, children and adolescents with type 1 diabetes have a much higher prevalence of cardiovascular risk factors compared to non-diabetic individuals. To prevent future cardiovascular events, achieving the best possible glycemic control, early detection of further risk factors, and adequate intervention are highly important.

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., (© 2011 John Wiley & Sons A/S.)

Objective: To estimate the prevalence of epilepsy and possible risk factors in children and adolescents with diabetes mellitus., Study Design: We conducted an observational cohort study based on the Diabetes Patienten Verlaufsdokumentation database including data from 45 851 patients (52% male) with type 1 diabetes mellitus, age 13.9 ± 4.3 years (mean ± SD) and duration of diabetes mellitus 5.4 ± 4.2 years. The database was searched for the concomitant diagnosis of epilepsy or epileptic convulsions and for antiepileptic medication., Results: A total of 705 patients with epilepsy were identified, giving a prevalence of 15.5 of 1000. A total of 375 patients were treated with antiepileptic medication, and 330 patients were without anticonvulsive therapy. Patients with epilepsy were younger at onset of diabetes mellitus and shorter than patients without epilepsy, and their weight and body mass index were comparable. No difference could be demonstrated for metabolic control, type of insulin treatment, insulin dose, and prevalence of B-cell specific autoantibodies. The frequency of severe hypoglycemia was lower in patients treated with antiepileptic medication. The risk for diabetic ketoacidosis was almost double in patients with epilepsy compared with patients with type 1 diabetes mellitus alone (P < .01)., Conclusion: Children and adolescents with diabetes mellitus show an increased prevalence of epileptic seizures. For unknown reasons, there is an association between epilepsy and diabetic ketoacidosis in children with type 1 diabetes mellitus., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals <3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals <3 years.

Objective: The aim of this study was to evaluate the prevalence of insulin under- and overdosing in paediatric patients., Research Design and Methods: Cross-sectional study including 241 patients (age 14.0 + 2.7 yr, 42.5% males) with type 1 diabetes from 21 diabetic outpatient clinics. Haemoglobin A1c (HbA1c), height, and weight were available from clinical records. Patients were interviewed with the Diabetes Self-Management Profile (DSMP) interview. T test, U test, and chi-squared test were used for comparison., Results: On the basis of the DSMP, 103 (42.7%) patients (group A) showed adherence to the therapeutic insulin regimen, while 71 (29.5%) patients (group B) confessed intentional over and/or under-dosing of insulin. Sixty-seven (27.8%) adolescents (group C) reported management problems leading to unintended inappropriate insulin dosages. In group B, 55 (22.8%) injected higher insulin doses and 58 (24.1%) omitted insulin. Patients of group B compared to group A were older 15.0 (±2.5) vs. 14.0 (±2.5) yr (p < 0.01), older at onset 9.5 (±3.6) vs. 8.3 (±3.8) yr (p = 0.05), were more often girls (69 vs. 45.6%), had a higher actual HbA1c (8.7 ± 1.7 vs. 7.8 ± 1.2%), and a higher average HbA1c in the previous year (8.3 ± 1.6 vs. 7.9 ± 1.2%) (p < 0.01). No significant differences could be found between group A and group C., Conclusion: Intentional overdosing of insulin is almost as prevalent in children and adolescents as insulin omission. Females are more at risk., (© 2011 John Wiley & Sons A/S.)

Objective: To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation., Research Design and Methods: The clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes., Results: WSD was diagnosed earlier than type 1 diabetes (5.4±3.8 vs. 7.9±4.2 years; P<0.001) with a lower prevalence of ketoacidosis (7 vs. 20%; P=0.049). Mean duration of remission in WSD was 2.3±2.4 vs. 1.6±2.1 in type 1 diabetes (NS). Severe hypoglycemia occurred in 37 vs. 7.9% (P<0.001). Neurologic disease progression was faster in the WSD group with a mean HbA1c>7.5% (P=0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P=0.028)., Conclusions: Endoplasmic reticulum stress-mediated decline of β-cells in WSD occurs earlier in life than autoimmune-mediated β-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease.

Objective: Diabetic ketoacidosis (DKA) remains a major cause of hospitalization and death in children and adolescents with established type 1 diabetes despite DKA preventing strategies. The aim of the study was to determine incidence and risk factors for DKA in a large cohort of young diabetic patients., Methods: This investigation uses the dpv-wiss base containing data on 28 770 patients with type 1 diabetes <20yr, from Germany and Austria. For each patient the most recent year of follow-up was evaluated. DKA was defined as pH < 7.3 and/or hospital admission as a result of DKA, excluding onset DKA., Results: Mean age of the study cohort was 13.96 ± 4.0 yr (47.9% females). A total of 94.1% presented with no episode, 4.9% with 1 episode, and 1.0% with recurrent DKA (≥2). When comparing these three groups, age (p < 0.01), HbA1c (p < 0.01), and insulin dose (p < 0.01) were significantly higher in patients with recurre nt DKA. Incidence of DKA was significantly higher in females (7.3 ± 0.5 vs. 5.8 ± 0.2; p = 0.03) and in patients with migration background (7.8 ± 0.6 vs. 6.3 ± 0.3; p = 0.02). No significant association was found with treatment type and diabetes duration., Conclusion: In a cohort of European paediatric diabetic patients, the rate of DKA was significantly higher in females and in children with migration background and early teenage years., (© 2011 John Wiley & Sons A/S.)

Objective: Although high levels of asymmetric dimethylarginine (ADMA) are associated with an increased risk for vasculopathy in adults, elevated ADMA concentrations also have been found in healthy young children. Patients with diabetes mellitus type 1 (DM1) are at risk for vasculopathy, and because the function of ADMA in the development of vascular symptoms is incompletely understood, we investigated ADMA concentrations in pediatric patients with DM1 compared with healthy age- and sex-matched individuals., Study Design: This cross-sectional study included 85 pediatric patients with DM1 and 89 age- and sex-matched healthy controls., Results: ADMA concentrations were significantly lower in the patients with DM1 and were inversely correlated with hemoglobin A1c concentrations., Conclusions: Besides its vasoprotective function, nitric oxide itself may exert oxidative stress by generating free radicals. In these circumstances, ADMA would protect the system from nitric oxide overproduction and perpetuation of oxidative stress. This theory is supported by the physiologically higher ADMA concentrations in healthy children. Thus, low ADMA concentrations in children with DM1 may be an indicator of impaired protection against oxidative stress., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies., Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity., Results: Data were available for 6 cohort and 25 case-control studies, including 11,955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I² = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children < 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I² = 23%)., Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged < 5 years. This finding could reflect increased exposure to infections in early life in later born children.

Objective: To evaluate the influence of biopsy-proven celiac disease (BPCD) on somatic development and metabolic parameters in children with type 1 diabetes mellitus (T1DM) in a multicenter survey., Study Design: Within the Diabetes Patienten Verlaufsdokumentationssystem-Wiss project, data of 41 951 patients with T1DM, aged <20 years (52% males, mean age 13.9 years; mean duration of diabetes 5.5 years) were collected in 297 centers in Germany and Austria from 1995 to 2009., Results: The number of BPCD (0.6% in 1995; 1.3% in 2008) has increased over time. Patients with BPCD were significantly younger at diabetes onset (5.9 vs 8.3 years), had a significantly lower weight standard deviation score (SDS); (0.20 vs 0.43) and height SDS (-0.28 vs -0.03) (P < .001, each) compared with patients without celiac disease. No differences were found in hemoglobin A1c or numbers of severe hypoglycemia. In a subgroup of 9805 patients (183 with BPCD) significantly lower height and weight SDS (P < .001) were still found after a 5-year follow-up., Conclusions: Screening for celiac disease is important in children with T1DM to prevent persistent growth failure., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To assess differences in congenital anomalies, infant mortality, and obstetrical complications as well as risk factors associated with an adverse pregnancy outcome in women with type 1 (T1DM) and type 2 diabetes mellitus (T2DM)., Methods: This observational study was performed at a university clinic and included a total of 200 singleton pregnancies between January 1995 and December 2006. Outcome measures comprise the prevalence of major congenital malformations, fetal losses, stillbirths, and neonatal deaths as well as the combined end point, adverse pregnancy outcome, and obstetrical complications., Results: Despite changes in prevailing risk factors, the rate of congenital anomalies and embryonic as well as perinatal death was comparable in type 1 diabetic women over time as well as between women with T1DM and T2DM. Outcome measures and risk factor profile were similar in women with preconception and newly diagnosed T2DM. Glycemic control and increased body mass index (BMI) during the first trimester were the strongest predictors of an adverse pregnancy outcome. Hemoglobin A1c (HbA1c) was higher in T1DM than in T2DM but similar in women with T1DM over time. BMI was highest in women with T2DM, followed by T1DM women of the most recent time period., Conclusions: In addition to HbA1c, other risk factors, especially high BMI, strongly influence pregnancy outcome. The higher prevalence of these risk factors in T2DM might compensate for the better glycemic control, resulting in a pregnancy outcome comparable to that of T1DM. Pregnancy outcome in T1DM remained unchanged over time, possibly because of the missing amelioration of HbA1c levels and the increasing BMI.

Objectives: Pathology of the regulative mechanisms of self seems to be connected with eating disorders (EDs). The present study aimed to explore the hypothesis that there are differences in self-regulation in adolescent girls with Type 1 diabetes with and without EDs., Design: A cross-sectional design was employed comparing patterns of self-regulation in adolescent girls with Type 1 diabetes with and without EDs in two eating status groups., Methods: For the presence of EDs, 76 adolescent girls with Type 1 diabetes were assessed. Of these, 23 were diagnosed with an ED. In addition, dimensions of self-regulation as conceptualized in terms of Kohuts' psychodynamic theory of self were assessed., Results: Adolescent girls with Type 1 diabetes and an ED were higher in three aspects of self-regulation - negative body self, object depreciation, and narcissistic gain from illness - in comparison with their peers without EDs., Conclusions: This study is the first to show evidence of deficits in self-regulation in adolescent girls with Type 1 diabetes and EDs. The importance of evaluating parameters of self-regulation for treatment planning for these youths is outlined.

Objectives: Characterization of children with type 1 diabetes (T1DM) regarding number and gender distribution of cardiovascular risk factors (cvRF) and of total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C ratio) for risk assessment., Methods: 33488 patients 200 mg/dL, >5.17 mmol/L; and/or HDL-C <35 mg/dL, <0.91 mmol/L; and/or LDL-C >130 mg/dL, >3.36 mmol/L), elevated systolic and/or diastolic blood pressure (BP) >or=90th percentile, obesity >97th percentile, active smoking, and HbA1c >or=7.5% were considered as cvRF., Results: 65% had no or 1 cvRF. HbA1c >/=7.5% was the most frequently occurring cvRF followed by BP >or=90th percentile, dyslipidemia, smoking, and BMI >97th percentile. Age at diabetic onset ranged from 7.7 to 9.2 years and diabetes duration from 4.1 to 6.6 years. CvRF showed differences in disfavour of females except smoking and HDL-C <35 mg/dL (0.91 mmol/L). Rate of females was 45% with 0 cvRF and 60% with 4 to 5 cvRF. TC/HDL-C ratio showed no clear association to the number of cvRF., Conclusions: 35% of a pediatric T1DM population develops 2 or more cvRF thus increasing their cv risk in adulthood. With increasing numbers of cvRF, the percentage of girls is rising from 45% to 60% which might contribute to an assimilation of survival rates in female and male adults. TC/HDL ratio does not predict the extent of cardiovascular risk in pediatric T1DM.

Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.

Objective: The aims of the study were to determine time trends in cardiovascular risk factors among young Austrian males between 1986 and 2005 and to examine socioeconomic and geographic differences., Methods: Data on Austrian conscripts were derived from the nationwide compulsory medical investigations held at military induction at 18 years of age. Four cohorts (1986-1990: n = 252,799; 1991-1995: n = 209,266; 1996-2000: n = 208,427; 2001-2005: n = 209,168) were examined with respect to their place of residence and level of education. Height, weight, waist circumference, blood pressure, serum total-cholesterol and triglycerides were measured. Mean body mass index (BMI) was calculated: overweight was defined as BMI between 25 and <30 and obesity as BMI >or= 30. The Chi-squared test and ANOVA were used to test group differences., Results: During the 20-year observation period the prevalence of overweight increased from 13.3% to 15.7% (p < 0.001) and that of obesity from 2.6% to 5.4% (p < 0.001); in accordance, mean BMI and waist circumference increased significantly. Blood pressure and serum total-cholesterol level decreased (p < 0.001) during the period studied, although triglyceride levels (p < 0.001) increased. A significant east-west gradient was identified for the prevalence of overweight and obesity, waist circumference and mean BMI, with lower values in the urban population compared with those of rural inhabitants. Mean BMI and the prevalence of overweight and obesity were higher in conscripts belonging to lower socioeconomic strata., Conclusion: Our study demonstrates a clear increase of mean BMI, waist circumference and the prevalence of overweight and obesity in Austrian male adolescents during the past 20 years. Conscripts from rural regions and with lower levels of education showed the highest values. The investigation of conscript health appears to be a useful tool for risk surveillance in the male population.

Background: Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes which is diagnosed in the first 6 months of life. Several studies in the last few years provide information on genetic causes for NDM., Objective: The aim of this study was to identify all patients with diabetes in the first 6 months of life through the Austrian Diabetes Register, which is available since 1989. A retrospective data analyses was performed to calculate the current incidence of NDM., Subjects and Methods: Ten patients were registered with diabetes onset within the first 6 months of life in the Austrian Diabetes Register. Evaluation of detailed clinical data was performed by sending a questionnaire to all diabetes centers., Results: Ten patients from nine different families with NDM were diagnosed in Austria from 1989 until September 2007. Seven patients (one male, six females) had transient NDM (TNDM), three (two males, one female) showed a permanent course [permanent neonatal diabetes mellitus (PNDM)]. One had immunodeficiency, polyendocrinopathy and enteropathy X-linked (IPEX) syndrome and another showed aplasia of the pancreas; no genetic etiology was found in the third case. In three out of seven patients with a transient course of NDM a genetic diagnosis was possible. Two female siblings had activating point mutations in the ABCC8 gene, although one patient had paternal uniparental isodisomy of chromosome 6q24. One patient's family did not consent to genetic testing., Conclusions: The incidence of NDM in Austria is 1/160 949, with an incidence of 1/ 536 499 for PNDM and 1/229 928 for TNDM.

Objective: The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders., Research Design and Methods: Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies., Results: Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I(2) = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates., Conclusions: There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.

Objective: To analyze the time trend of the nationwide incidence of type 2 diabetes in children and adolescents < or = 15 years of age compared with type 1 diabetes between 1999 and 2007 in Austria., Study Design: In a prospective, population-based incidence study, all newly diagnosed patients with diabetes < or = 15 years of age were registered by the Austrian Diabetes Incidence Study Group. The Diabetes type was classified on the basis of clinical and laboratory findings according to ADA criteria. Time trends were estimated by linear regression models., Results: During the observation period, 1881 patients with type 1 diabetes and 34 patients with type 2 diabetes could be identified. Sixty-two percent of patients with type 2 diabetes were female, 56% had a positive family history for type 2 diabetes, and 74% presented with diabetes-specific symptoms. The incidence of type 1 diabetes in Austria increased from 12.0 to 18.4/100,000 (P < .001) and the incidence of type 2 diabetes remained stable below 0.6/100 000 (P = .706)., Conclusions: The incidence of type 2 diabetes in Austrian children is 10-fold lower than reported in other regions and did not increase over the last 8 years. During the same time period, a significant rise in the incidence of type 1 diabetes was observed.

Objective: The objective of this study was to evaluate whether very young children develop more dermatological complications during insulin pump treatment compared with school children., Study Design: Cross-sectional study in 78 consecutive children using insulin pump treatment >4 months., Results: Children in group A [n = 40, 28 males (M) and 12 females (F)] were 2.3 +/- 1.3 yr (+/-SD) and those in group B (n = 38, 13 M and 25 F) were 11.0 +/- 2.9 yr old at the start of continuous subcutaneous insulin infusion (CSII). The mean duration of CSII was similar in both groups (23.6 +/- 16.5 months in group A and 21.8 +/- 16.1 in group B). The most common dermatological complications were scars <3 mm (50% in group A vs. 71% in group B, p < 0.05) and lipohypertrophic areas at the insertion sites (45% in group vs. 47% in group B). Local abscesses and blisters were rare findings in both groups (7.5-12%), none leading to interruption or stop of CSII., Conclusions: Dermatological side effects during CSII are not more frequent or severe in very young diabetic children compared with diabetic children in school age.

Objective: Type 1 diabetes mellitus (T1DM) is associated with other autoimmune diseases such as celiac disease (CD) and Hashimoto thyroiditis. The aim of this study was to evaluate the screening frequency for CD and thyroid antibodies in a multicentre survey., Methods: The Diabetes Patienten Verlaufsdokumentationssystem (DPV) initiative is based on standardized, prospective, multicentre documentation in children and adolescents with diabetes. Data from 31,104 patients <18 yr of age (52% males, mean age 13.1 yr) with T1DM from 177 paediatric centres in Germany and Austria from 1995 until 2007 were analysed., Results: Of 31,104 patients, 16,994 patients (55%) were screened at least once for CD. In 1995, 44% of the patients were screened for CD compared with 68.6% in 2006. Annual screening for CD has also increased (11.9% in 1995 compared with 43.6% in 2006). Eleven per cent of the patients had positive antibodies for CD. Patients with positive antibodies were significantly younger at diabetes onset and had a significantly longer duration of diabetes (p < 0.001). Compared with screening for CD, screening for thyroid antibodies was performed more frequently (at least once in 62% of the patients). Fifteen per cent of the patients had positive thyroid antibodies. Screening for thyroid antibodies also increased from 62.6 to 72.9%, and annual screening frequency increased from 15.9 to 48.9%., Conclusion: Screening for associated autoimmune diseases in children with T1DM has increased during the past decade. Eleven per cent of the patients had positive CD-specific antibodies, and 15% had positive thyroid antibodies. Screening for thyroid antibodies is performed more frequently than screening for CD.

Objective: To assess the influence of gluten-free diet (GFD) compliance on the quality of life (QOL) of adolescents with coeliac disease (CD), and the impact of patient's age at time of diagnosis., Study Design: Participants included 365 subjects: 283 adolescents (10-20 years old) with biopsy-proven CD and 82 adolescents without a chronic condition matched for age, sex, education, and social status. Their subjective QOL-comprising physical, mental, and social dimensions as defined by the World Health Organization-was measured and has been analyzed according to compliance status and age at CD diagnosis., Results: Adolescents noncompliant with GFD reported a lower general QOL, more physical problems, a higher burden of illness, more family problems, and more problems in leisure time than adolescents who are compliant with GFD. More frequent GFD transgressions were associated with poorer QOL. Higher problem anticipation and higher feelings of "ill-being" were found in the noncompliant group. No differences between compliant patients with CD and adolescents without any chronic condition were found in all QOL aspects. Adolescents with a late CD diagnosis showed more problems at school and in social contact with peers, as well as worse physical health and higher CD-associated burden., Conclusions: Compliance with GFD is an essential factor to obtain optimal QOL. Psychosocial and educational support should be provided for patients having difficulties strictly adhering to GFD. Early CD onset and diagnosis is associated with better physical health, lower CD-associated burden and fewer social problems, indicating the importance of the earliest CD diagnosis possible.

Childhood overweight and obesity--especially among migrant children--are health problems in several European countries. The prevalence rates of overweight and obesity among 936 migrant boys of low socio-economic status from Turkey and former Yugoslavia were compared with those of Austrian boys in Vienna. In the longitudinal study, children were measured at the ages of 6, 10 and 15 years. Weight status was estimated by means of the body mass index and percentile curves were used for weight status classification. The prevalence of overweight and obesity was high among migrant boys as well as Austrian boys at all age groups. Ten-year-old boys from Yugoslavia exhibited the highest percentage of overweight (nearly 38%). The lowest percentage of overweight was among 6-year-old Austrian boys (17.2%). Being overweight or obese at the age of 6 years increased the risk of being overweight at 10 and 15 years significantly (p<0.001). This was true of all groups independent of migrant status. The impact of migrant status on weight status at the ages of 10 and 15 was not significant. Therefore, although migrant boys from former Yugoslavia exhibited the highest rates of overweight and obesity, migrant status is not associated significantly with an increased prevalence of obesity in this sample characterized by a generally low socio-economic status. Prevention should start as early as possible for all children, since overweight tends to persist from childhood into adolescence independent of migrant status.

Aim: To assess the neurological and clinical long-term outcome of patients diagnosed with congenital hyperinsulinism (CHI) in Austria., Patients and Methods: Fourteen patients diagnosed with CHI (1978-2000) were investigated retrospectively by reviewing hospital records. Thirteen of them were evaluated with either a questionnaire or clinical, neurological and biochemical investigations (age at evaluation 4.2-25.5 years) in a follow-up study in the year 2004., Results: Fifty percent of the patients needed a pancreatectomy. The prevalence of mental retardation was 31%, of epilepsy 15% and of pancreatic insufficiency 14%. None of our patients had developed diabetes mellitus. Additionally the prevalence of obesity was 43% in patients after pancreatectomy. Sixty-nine percent of the patients had no further treatment at the time of follow-up., Conclusion: Despite early diagnosis and intensive treatment, 31% of the patients presented with mental retardation.

Background: To investigate the rapid increase in incidence of type 1 diabetes mellitus (T1DM) in children <5 yr in Austria., Methods: Data of children born between 1989 and 2005 (n = 444) from the T1DM children incidence registry were linked with birth certificates (n = 1 407 829)., Results: Age of mother, level of education, birth weight, birth length, body mass index, and APGAR score at 10 min were not significant. Boys have about 25% higher risk than girls [hazard ratio = 0.75, 95% confidence interval (CI): 0.62-0.91]. The risk of developing diabetes increases over time significantly (1989-1991 vs. 2001-2005, hazard ratio = 2.86, 95% CI: 2.07-3.94). The linear effect of parity is borderline significant (p = 0.045), with lower risks for second and later born siblings. Marital status is significant [hazard ratio = 0.73, 95% CI: 0.57-0.90)]. Native-born children exhibit twice as high risk as non-native children (hazard ratio = 0.51, 95% CI: 0.37-0.71). Birth weight shows a positive but not significant effect on risk of T1DM., Conclusions: In this very young and rapidly increasing cohort of diabetic children <5 yr of age, no association with birth weight but with year of birth, gestational age, nationality and parity could be observed.

Objective: Arterial blood pressure was followed in 868 patients with type 1 diabetes aged 6.0-19.9 years in 95 centers in Germany and Austria., Research Design and Methods: European blood pressure reference data for 28,043 children and adolescents were used with respect to age and sex. Data were stratified into three groups: prepubertal, pubertal, and postpubertal., Results: Up to 4% of the participants in the younger age-groups and 13.9% of the postpubertal patients exhibited blood pressure values >97th centile. Blood pressure levels correlated with A1C level and BMI Z score. Tracking of blood pressure revealed that children with elevated blood pressure had higher blood pressure in adolescence and young adulthood., Conclusions: Patients with higher blood pressure in childhood showed elevated blood pressure later in life. We need to focus on the diagnosis of hypertension in children with type 1 diabetes and to study the efficacy of early intervention.

In a prospective population-based incidence study all newly diagnosed type 1 diabetic patients 0-<15 years of age were registered by the Austrian Diabetes Incidence Study Group. The nationwide incidence of type 1 diabetes between 2000-2005 was compared with the previously published incidence rates. Long-term trends as well as seasonal trends were estimated by Poisson regression models. A total of 3,599 incident cases (1,908 boys; 1,691 girls) were identified. Case ascertainment was >92%. The overall incidence rate doubled from 7.3 (95% CI; 6.8-7.9)/100,000 in the period 1979-84 to 14.6 (95% CI, 13.7-15.4)/100,000 in the time period 2000-2005. A significant increase during the observation period of 26 years could be demonstrated in all age groups and both sexes (p<0.01), with the steepest increment during the last 5 years. Until 1994 the incidence rate in children 0-<5 years was rather stable, but afterwards increased dramatically with 9.2% (95% CI, 5.2-13.4) annually. Despite this steep increase in time trend, we did not observe a seasonal variation in this age group (0-<5) in contrast to significant seasonal variations in the groups 5-<10 and 10-<15 years of age. Over the past 26 years incidence of type 1 diabetes in childhood increased clearly in Austria. The steepest rise was observed in the last 5 years and in the younger age groups.

Background/aims: To study the 2-year course of children and adolescents with type 2 diabetes mellitus (T2DM) in general practice to present (1) the treatment modalities, (2) patient adherence, and (3) the occurrence of comorbidities., Methods: HBA1c, lipids, blood pressure, treatment modalities, occurrence of retinopathy and nephropathy were analyzed in 129 children and adolescents with T2DM (median age 13.4 years, 75% female) in specialized diabetes centers in Germany., Results: Seventy-eight (60%) children dropped out of care after a mean of 7.1 months. Drug treatment was not stopped in any of the 64 children initially treated with antidiabetic drugs. Sixteen (12%) children were treated solely by lifestyle intervention over the 2-year course. In the 51 children with complete follow-up, median HbA1c was 7.7% at diagnosis and 6.3% after 2 years. Less than 5% of all children were treated with antihypertensive or lipid-lowering drugs, while 65% suffered from hypertension and 44% from dyslipidemia. Over the course of the disease, retinopathy was not observed, while microalbuminuria occurred in 25%., Conclusions: In general practice, many children and adolescents with T2DM were lost of follow-up. Lifestyle intervention as sole treatment was not often useful for long-term metabolic control. Dyslipidemia and hypertension were seldom treated as recommended., ((c) 2007 S. Karger AG, Basel)