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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Schober E, Wagner G, Berger G, Gerber D, Mengl M, Sonnenstatter S, Barrientos I, Rami B, Karwautz A, Fritsch M, on behalf of the Austrian Diabetic Incidence Study Group. 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. [ABSTRACT FROM AUTHOR]

Fritsch M, Rosenbauer J, Schober E, Neu A, Placzek K, Holl RW. 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 - 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. [ABSTRACT FROM AUTHOR]

Schwab KO, Doerfer J, Marg W, Schober E, Holl RW. 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 ≤18 years were included in this cross-sectional analysis and placed into 5 categories by their number of cvRF. Dyslipidemia (TC >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) ≥90th percentile, obesity >97th percentile, active smoking, and HbA1c ≥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 ≥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. [ABSTRACT FROM AUTHOR]

Wiedemann B, Schober E, Waldhoer T, Koehle J, Flanagan SE, Mackay DJG, Steichen E, Meraner D, Zimmerhackl LB, Hattersley AT, Ellard S and Hofer S. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]