Association of insulin-manipulation and psychiatric disorders: A systematic epidemiological evaluation of adolescents with type 1 diabetes in Austria.

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.

Comorbidity of attention deficit hyperactivity disorder and type 1 diabetes in children and adolescents: Analysis based on the multicentre DPV registry.

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.

Depression, metabolic control, and antidepressant medication in young patients with type 1 diabetes.

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.

Effects of high-dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial.

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.

Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV registries.

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.

Hemoglobin A1c Levels and risk of severe hypoglycemia in children and young adults with type 1 diabetes from Germany and Austria: a trend analysis in a cohort of 37,539 patients between 1995 and 2012.

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.

Algorithm-based cholesterol monitoring in children with type 1 diabetes.

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.

Diabetic ketoacidosis at diagnosis in Austrian children: a population-based analysis, 1989-2011.

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.

HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database.

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 ß-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 ß-cell autoimmunity or HLA-DR genetic risk likely had either T1.5DM or 'double diabetes' or an unknown diabetes type.

Association of epilepsy and type 1 diabetes mellitus in children and adolescents: is there an increased risk for diabetic ketoacidosis?

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.

Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies.

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.

Prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes in Austria.

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.

Anthropometry, metabolic control, and follow-up in children and adolescents with type 1 diabetes mellitus and biopsy-proven celiac disease.

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.

Low levels of asymmetric dimethylarginine in children with diabetes mellitus type I compared with healthy children.

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.

Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicentre database.

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.

Prevalence of intentional under- and overdosing of insulin in children and adolescents with type 1 diabetes.

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.

Type 1 diabetes and epilepsy: efficacy and safety of the ketogenic diet.

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.

Characterization of 33 488 children and adolescents with type 1 diabetes based on the gender-specific increase of cardiovascular risk factors.

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.

Incidence of neonatal diabetes in Austria-calculation based on the Austrian Diabetes Register.

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.

Incidence and time trend of type 1 and type 2 diabetes in Austrian children 1999-2007.

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.