Determinants of glycaemic outcome in the current practice of care for young people up to 21 years old with type 1 diabetes under real-life conditions.

AIM: To determine factors influencing the success of treatment for type 1 diabetes, defined as HbA1c < 58 mmol/mol (<7.5%), in a large paediatric cohort under real-life conditions. METHODS: This is a monocentric observational study analysing the determinants of glycaemic outcome (sex, age, comorbidities, sociodemographic factors, diabetes technology) in an entire cohort of people with diabetes aged up to 21 years. Glycaemic outcome was defined as an individual's median HbA1c and the prevalence of acute complications over this period. RESULTS: Of 700 young people with type 1 diabetes [age 13.6 years (range: 1.4-20.9 years); diabetes duration 5.8 years (range: 0.1-18.3 years)], 63% were using an insulin pump and 32% any type of continuous glucose monitoring. Mean HbA1c was 61 mmol/mol [95% confidence interval (CI) 60-62; 7.7%, 95% CI 7.5-7.8]. Some 63% of children aged < 12 years reached HbA1c (58 mmol/mol (<7.5%) compared with 43% of older participants. The prevalence of severe hypoglycaemia was 2.41 events and that of diabetic ketoacidosis 1.4 events per 100 person-years. Neither type of insulin therapy nor use of continuous glucose monitoring, sex or comorbidity with coeliac disease or thyroiditis was significantly associated with glycaemic outcome. However, age, diabetes duration, having a father not born in Germany, psychiatric comorbidities and family structure were associated with HbA1c . CONCLUSIONS: Current technologies and a multidisciplinary team approach allow high numbers of children and adolescents to realize tight glycaemic control with a low prevalence of acute complications. However, age-related challenges, sociodemographic factors and psychological comorbidities are barriers to achieving best possible glycaemic outcome.

Physical activity is associated with lower insulin and C-peptide during glucose challenge in children and adolescents with family background of diabetes.

AIMS: Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory risks in children and adolescents with a family background of Type 1 diabetes or gestational diabetes. METHODS: Valid MVPA measurements, made with accelerometers, were available from 234 participants (median age, 10.2 years) who had a first-degree relative with either Type 1 or gestational diabetes. Anthropometric and metabolic measurements were made and cytokines measured, and were correlated with MVPA measurements, with stepwise adjustment for confounding factors, in a cross-sectional analysis. RESULTS: MVPA was negatively associated with insulin and C-peptide during challenge with an oral glucose tolerance test. MVPA was also significantly positively associated with the insulin sensitivity index, whereas no consistently significant associations were found between MVPA and BMI, blood pressure or cytokine levels. DISCUSSION: Our findings indicate that physical activity may have beneficial effects on insulin and C-peptide metabolism in children and adolescents with a family background of diabetes, but show no evidence of a protective association with other health-related outcomes.

Seasonality at the clinical onset of type 1 diabetes-Lessons from the SWEET database.

BACKGROUND: Seasonality at the clinical onset of type 1 diabetes (T1D) has been suggested by different studies, however, the results are conflicting. This study aimed to evaluate the presence of seasonality at clinical onset of T1D based on the SWEET database comprising data from 32 different countries. METHODS: The study cohort included 23 603 patients (52% males) recorded in the international multicenter SWEET database (48 centers), with T1D onset ≤20 years, year of onset between 1980 and 2015, gender, year and month of birth and T1D-diagnosis documented. Data were stratified according to four age groups (<5, 5-<10, 10-<15, 15-20 years) at T1D onset, the latitude of European center (Northern ≥50°N and Southern Europe <50°N) and the year of onset ≤ or >2009. RESULTS: Analysis by month revealed significant seasonality with January being the month with the highest and June with the lowest percentage of incident cases (P < .001). Winter, early spring and late autumn months had higher percentage of incident cases compared with late spring and summer months. Stratification by age showed similar seasonality patterns in all four age groups (P ≤ .003 each), but not in children <24 months of age. There was no gender or latitude effect on seasonality pattern, however, the pattern differed by the year of onset (P < .001). Seasonality of diagnosis conformed to a sinusoidal model for all cases, females and males, age groups, northern and southern European countries. CONCLUSIONS: Seasonality at T1D clinical onset is documented by the large SWEET database with no gender or latitude (Europe only) effect except from the year of manifestation.

[Closed-Loop at night for the treatment of type 1 diabetes]. / "Closed Loop": Wann kommt die künstliche Bauchspeicheldrüse für Typ-1-Diabetes?

This mini-review describes the latest efforts, challenges, and experience of using automated insulin delivery systems at outpatient settings and home studies. Predictive low glucose management (PLGM) may help prevent hypoglycemia by stopping insulin pump delivery based on predicted sensor glucose values. In silico modeling and early feasibility data demonstrate that PLGM may further reduce the severity of hypoglycemia beyond that already established for algorithms that use a threshold-based suspension. Recent studies have shown that an closed-loop system can improve glucose control and reduce nocturnal hypoglycemia. In the multinational, multicenter DREAM project patients at a diabetes camp who were treated with an artificial-pancreas system had less nocturnal hypoglycemia and tighter glucose control than when they were treated with a sensor-augmented insulin pump. Studies using closed-loop systems at patients' home are currently being carried out. The preliminary results of these experiments are encouraging and enhance our confidence in this tool as suitable for use in clinical daily practice.

Diabetic retinopathy in type 1 diabetes-a contemporary analysis of 8,784 patients.

AIMS/HYPOTHESIS: The aim of this study was to analyse the risk profile for diabetic retinopathy under real-life conditions in a large cohort of patients with type 1 diabetes. METHODS: Patients (n = 18,891) with childhood, adolescent or adult onset of type 1 diabetes from the prospective German Diabetes Documentation System survey were analysed. A total of 8,784 patients fulfilled the inclusion criterion, which was availability of retinopathy status. Retinopathy grading (any retinopathy, advanced retinopathy), treatment regimens and risk factors were prospectively recorded and tested as covariates by Kaplan-Meier analysis and logistic regression. RESULTS: Any retinopathy was present in 27.4% and advanced retinopathy (severe non-proliferative or proliferative diabetic retinopathy) in 8.0% of the cohort. After 40 years of diabetes, the cumulative proportion of patients with any retinopathy and advanced retinopathy was 84.1% and 50.2%, respectively. In multiple regression analysis, risk factors for any retinopathy were diabetes duration (OR 1.167 per year), HbA(1c) >7.0% (53 mmol/mol) (OR 2.225), smoking (OR 1.295) and male sex (OR 1.187) (p < 0.0001 for all). Young age at onset (5 vs 15 years at disease onset) was protective (0.410, p < 0.0001). No glycaemic threshold was detected for retinopathy protection. Risk factors for advanced retinopathy were duration (1.124 per year, p < 0.0001), male sex (1.323, p = 0.0020), HbA(1c) >7.0% (53 mmol/mol) (1.499, p < 0.0001), triacylglycerol >1.7 mmol/l (1.398, p = 0.0013) and blood pressure >140/90 mmHg (1.911, p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of retinopathy remains significant in type 1 diabetes. Any improvement of metabolic control and non-smoking is protective, while hypertension affects progression to severe levels under real-life conditions. These data reinforce the validity of multifactorial concepts for morbidity protection in type 1 diabetes.

[Clinical parameters for molecular testing of Maturity Onset Diabetes of the Young (MODY)]. / Molekulargenetische Diagnostik bei Verdacht auf Maturity Onset Diabetes of the Young (MODY): Klinische Parameter zur Entscheidungshilfe.

BACKGROUND: Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening. METHODS: Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria. RESULTS: Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment. CONCLUSION: In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment.

[Successful treatment with liraglutide in type 1 diabetes and MODY]. / Erfolgreicher Einsatz von Liraglutid bei Typ-1-Diabetes und MODY.

HISTORY AND CLINICAL FINDINGS: A 22 year old obese woman with type 1 diabetes for 17 years and poor metabolic control despite continuous insulin infusion (case 1). Case 2 was a 16 year-old girl of normal weight in whom diabetes mellitus type 1 was diagnosed accidentally. Her 54 year old father was and had been treated for diabetes mellitus type 1 for 10 years. He was poorly controlled and associated with polyneuropathy and history of myocardial infarction (case 3). INVESTIGATIONS: In Case 1 the C-peptide test was negative, glutamic acid decarboxylase- and IA2-antibodies were not demonstrated. Cases 2 and 3 showed normal C-peptide, tests for GAD-, IA2- and ICA antibodies were negative. A nucleotid substitution in intron 1 of the HNF-4α gene was demonstrated. TREATMENT AND COURSE: All three patients were treated with liraglutide. There was a reduction in HbA(1c), glucose fluctuations, hypoglycaemia, daily insulin dose and body weight, as well as an improvement of well-being and quality of life. CONCLUSION: These case reports indicate that GLP-1 analogs may reduce postprandial and fasting glucose levels in non-type 2 diabetic patients, independently or residual beta cell function. Further studies are needed to evaluate the benefits of treatment with liraglutide in patients with type 1 or type 3 diabetes.

Sensor-augmented pump therapy from the diagnosis of childhood type 1 diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment.

AIMS/HYPOTHESIS: The value of managing children with type 1 diabetes using a combination of insulin pump and continuous glucose monitoring starting from diagnosis for improving subsequent glycaemic control and preserving residual beta cell function was determined. METHODS: A total of 160 children (aged 1-16 years, mean ± SD: 8.7 ± 4.4 years; 47.5% girls) were randomised to receive insulin pump treatment with continuous glucose monitoring or conventional self-monitoring blood glucose measurements. The primary outcome was the level of HbA(1c) after 12 months. Other analyses included fasting C-peptide, glycaemic variability, sensor usage, adverse events, children's health-related quality of life and parent's wellbeing. RESULTS: HbA(1c) was not significantly different between the two groups, but patients with regular sensor use had lower values (mean 7.1%, 95% CI 6.8-7.4%) compared with the combined group with no or low sensor usage (mean 7.6%, 95% CI 7.3-7.9%; p=0.032). At 12 months, glycaemic variability was lower in the sensor group (mean amplitude of glycaemic excursions 80.2 ± 26.2 vs 92.0 ± 33.7; p=0.037). Higher C-peptide concentrations were seen in sensor-treated 12- to 16-year-old patients (0.25 ± 0.12 nmol/l) compared with those treated with insulin pump alone (0.19 ± 0.07 nmol/l; p=0.033). Severe hypoglycaemia was reported only in the group without sensors (four episodes). CONCLUSION/INTERPRETATION: Sensor-augmented pump therapy starting from the diagnosis of type 1 diabetes can be associated with less decline in fasting C-peptide particularly in older children, although regular sensor use is a prerequisite for improved glycaemic control. TRIAL REGISTRATION: ISRCTN.org ISRCTN05450731 FUNDING: Medtronic International Trading Sàrl, Tolochenaz, Switzerland.

Genetic risk markers related to diabetes-associated autoantibodies in young patients with type 1 diabetes in berlin, Germany.

AIMS: To determine the prevalence of genetic risk markers of type 1 diabetes (T1D) in children diagnosed at a single centre in Germany and to assess their relation to diabetes-associated autoantibodies. METHODS: Blood samples from 243 paediatric patients were genotyped for the high-risk HLA haplotypes DR3-DQ2 (DQA1*05-DQB1*02) and DR4-DQ8 (DRB1*0401/2/4/5-DQB1*0302) and PTPN22 C1858 T polymorphism. The patients (51.4% male) were diagnosed with T1D at a median age of 8.6 y. The T1D-related autoantibodies GADA, IAA and IA-2A were analysed at diagnosis. RESULTS: 166 patients (68.6%) carried the DR3-DQ2, 114 (47.1%) the DR4-DQ8 haplotype, while 41 (16.9%) patients were negative for both. The PTPN22 CC genotype was detected in 177 (72.8%), CT in 58 (23.9%) and TT in eight (3.3%) patients, respectively. The prevalence of T1D-related autoimmunity was 77.0% for IA-2A, 71.6% for GADA and 43.6% for IAA. There were no differences between patients with and without the 1858 T allele in terms of the frequency, levels or number of autoantibodies, but the former were younger at diagnosis than the latter (p=0.002), IA-2A were positively related to HLA DR4-DQ8 (p=0.004) and inversely associated with HLA DR3-DQ2 (p=0.002). GADA-positive patients were older than those without GADA (p=0.004). In multivariate logistic regression analysis including gender and age as confounding variables, DR4-DQ8 (OR 2.56, 95%CI 1.35-4.86) and DR3-DQ2 (OR 0.36, 95%CI 0.19-0.68) were the only independent predictors of IA-2A positivity. CONCLUSION: The prevalence of genetic risk markers in Berlin children with T1D is found to be comparable to other Caucasian T1D populations. The presence of IA-2A at diagnosis is strongly associated with the HLA risk haplotypes, but not with PTPN22 polymorphism.

Reducing glycaemic variability in type 1 diabetes self-management with a continuous glucose monitoring system based on wired enzyme technology.

AIMS/HYPOTHESIS: This study was designed to investigate the use and impact of a continuous glucose monitoring system (the FreeStyle Navigator) under home-use conditions in the self-management of type 1 diabetes. METHODS: A 20 day masked phase, when real-time data and alarms were not available, was compared with a subsequent 40 day unmasked phase for a number of specified measures of glycaemic variability. HbA(1c) (measured by DCA 2000) and a hypoglycaemia fear survey were recorded at the start and end of the study. RESULTS: The study included 48 patients with type 1 diabetes (mean age 35.7 +/- 10.9, range 18-61 years; diabetes duration 17.0 +/- 9.5 years). Two patients did not complete the study for personal reasons. Comparing masked (all 20 days) and unmasked (last 20 days) phases, the following reductions were seen: time outside euglycaemia from 11.0 to 9.5 h/day (p = 0.002); glucose SD from 3.5 to 3.2 mmol/l (p < 0.001); hyperglycaemic time (>10.0 mmol/l) from 10.3 to 8.9 h/day (p = 0.0035); mean amplitude of glycaemic excursions (peak to nadir) down by 10% (p < 0.001); high blood glucose index down by 18% (p = 0.0014); and glycaemic risk assessment diabetes equation score down by 12% (p = 0.0013). Hypoglycaemic time (<3.9 mmol/l) decreased from 0.70 to 0.64 h/day without statistical significance (p > 0.05). Mean HbA(1c) fell from 7.6 +/- 1.1% at baseline to 7.1 +/- 1.1% (p < 0.001). In the hypoglycaemia fear survey, the patients tended to take less snacks at night-time after wearing the sensor. CONCLUSIONS/INTERPRETATION: Home use of a continuous glucose monitoring system has a positive effect on the self-management of diabetes. Thus, continuous glucose monitoring may be a useful tool to decrease glycaemic variability.

Mating in parents of type 1 diabetes families as a function of the HLA DR-DQ haplotype.

AIM: The Major Histocompatibility Complex (MHC) region on chromosome 6p21 (IDDM1) contributes about half of the familial clustering of type 1 diabetes (T1D). Several studies have revealed that highly polymorphic genes within the MHC may associate with the mating choice. Our study should determine whether a specific mating effect is detectable in T1D families as a function of human leucocyte antigen (HLA) DR-DQ, which could contribute to disease susceptibility. METHODS: We analysed the parental HLA-DR genotypes in 829 diabetic families. The families derive from the Type 1 Diabetes Genetics Consortium (T1DGC) in addition to those of our own centre and the original UK, US and SCAND diabetic families. RESULTS: A total of 307 of 829 parental couples (37.0%) were matched for at least one known T1D risk haplotype (DR3 or DR4), which is significantly less than the expected 374.9 (45.2%), derived from population genotype frequencies (p < 0.0009). Parents share less susceptibility haplotypes and rather complement each other as both carry one different risk haplotype (DR3 or DR4). The number of such parental couples was significantly higher than expected (293 vs. 223.4; p < 0.0003). All non-transmitted DR haplotype pairs were also analysed. More often than expected, both parents did not transmit DR1 (94 vs. 59.1; p < 0.003) and DRy (y: not DR1, not DR3, not DR4; 63 vs. 30.3; p < 0.0005). In contrast, the parental non-transmitted pair of haplotypes DR1-DRy was observed to a far lesser extent than expected (26 vs. 84.7; p < 10(-8)). These observations were only made in multiplex families, whereas in simplex families, no deviation from the expected frequencies was observed. CONCLUSIONS: Our data are consistent with the conclusion that genes in the HLA region may influence the mating choice in parents of T1D patients, thus contributing to familial clustering of T1D in multiplex families. This may indicate a different parental background of multiplex compared with simplex T1D families.

MHC-environment interactions leading to type 1 diabetes: feasibility of an analysis of HLA DR-DQ alleles in relation to manifestation periods and dates of birth.

AIM: The region on chromosome 6p21 (IDDM1) confers the largest part of genetic susceptibility to type 1 diabetes (T1D) with particular human leucocyte antigen (HLA) alleles predisposing and others protecting from it. As T1D is primarily a "sporadic" disease, the pathophysiology must involve gene-environment interactions. We searched for indirect evidence for such major histocompatibility complex (MHC)-environment interactions by asking two questions: (i) can the degree of an HLA association vary over time periods? and (ii) if a prenatal event like an intrauterine infection - that might cluster in seasons - leads to differences of HLA associations in patients with particular birth months? METHODS: We screened the Type 1 Diabetes Genetics Consortium (T1DGC) database (in addition our own database and the original UK, US and SCAND databases) for MHC DR-DQ and CTLA4 associations. First, we separated the groups of patients with onset of disease before 1980 in comparison with onset after 1980. Second, we analysed the data according to dates of birth (grouped in months). Not all patients' dates of birth or manifestation periods were available, leading to different group sizes. There were 282 patients analysed for manifestation periods and 329 for birth month. RESULTS: The cohorts of manifestation before 1980 demonstrated a significantly lower frequency of DQ2/X (2 vs. 14.2%; p = 0.03). There was a trend for DQ8/x to be more frequent for manifestations before 1980 (34 vs. 21.6%; p < 0.10). Other alleles did not differ significantly. The months of birth were not evenly distributed. Significant deviations from the whole group were seen in August (DQ2/8 trough and DQx/x high), whereas birth in September was more frequent in DQ8/x or DQ8/8 carriers. This pattern was significantly different from the expected distribution of months at birth (13.9 vs. 7.6%; p < 0.04). CONCLUSIONS: We demonstrate the feasibility of an analysis that searches for indirect evidence of gene-environment interactions. These preliminary data need to be confirmed in larger data sets.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries.

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

Results of a randomised controlled cross-over trial on the effect of continuous subcutaneous glucose monitoring (CGMS) on glycaemic control in children and adolescents with type 1 diabetes.

OBJECTIVE: To study the feasibility and the influence on glycaemic control of continuous glucose monitoring (CGMS) in young patients with type 1 diabetes. DESIGN AND METHODS: A double-blinded, cross-over study was performed in 30 children (median age 11.1 years [range: 2.3 - 16.3], diabetes duration 2.1 years [0.2 - 7.1]). Patients were randomised into an open (A) or blind study arm (B). Both groups performed standardised self-monitoring blood glucose (SMBG) and received CGMS at the beginning of the study, at 3 and 6 months, each. In the blinded arm, patients and investigator were concealed from CGMS data. After 3 months, open and blinded study arms crossed over. Average glucose values and area under the glucose curve (AUC) per 24 h, above 180 and below 60 mg/dl were calculated from CGMS. Haemoglobin A1c (HbA1c) was measured at each study point. RESULTS: Despite comparable clinical characteristics between the 15 patients of each arm, mean HbA1c was slightly lower in arm A than in B at baseline (7.8 +/- 1.2 % vs. 8.4 +/- 1.1 %, p = 0.148), at 3 months (7.8 +/- 1.1 % vs. 8.3 +/- 1.1 %, p = 0.233), and significantly lower at 6 months (7.6 +/- 1.1 % vs. 8.5 +/- 0.9 %, p = 0.026). However, no significant change of HbA1c occurred within each arm (A, p = 0.183 and B, p = 0.823), irrespectively whether CGMS data were blinded or not. Likewise, mean glucose and hyper- or hypoglycaemia values did not change significantly. CONCLUSIONS: In this setting, CGMS did not decisively influence glycaemic control of a total study cohort. More frequent use of CGMS at shorter intervals in single patients with hyper- or hypoglycaemic problems may be of greater value than SMBG.

Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty.

AIMS: To investigate the natural history and incidence of autoimmune thyroiditis (AIT) in paediatric patients with type 1 diabetes (T1D). METHODS: Since 1990, annual screening for thyroid disease has been performed in children and adolescents with T1D. Antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-TG) as well as TSH were measured in 659 patients (54.3% boys). In 126 patients, anti-TPO and anti-TG levels were followed at yearly intervals from onset up to five years of T1D. Anti-TPO above 30 U/ml and anti-TG above 20 U/ml were considered positive, values above 100 U/ml as significantly raised and indicative of AIT. L-thyroxine treatment was started if TSH was higher than 4.5 microU/ml and/or thyroid gland enlargement on thyroid ultrasound was present. RESULTS: At initial screening, 15.4% of patients had raised anti-TPO and 14.4% anti-TG. Girls had more frequently raised antibodies than boys. Sixty two patients (9.4%, 61% girls) required treatment with L-thyroxine. The cumulative incidence (SE) of AIT after 10 years of diabetes was 0.14 (0.02), being significantly higher in females (0.18 (0.03)), particularly after the age of 12 years. At T1D onset, positive anti-TPO and anti-TG were present in 21 of 126 patients (16.7%), each. All patients with significantly increased values of anti-TPO (n = 17, 148-5340 U/ml) and anti-TG (n = 11, 140-2000 U/ml) at T1D onset remained positive during the following five years. CONCLUSIONS: For early detection of autoimmune thyroiditis in children with T1D, measurement of anti-TPO and TSH at T1D onset and in yearly intervals after the age of 12 years is recommended.

[Diabetes in childhood: everyday burden and professional consequences for parents]. / Diabetesmanifestation im Kindesalter: Alltagsbelastungen und berufliche Entwicklung der Eltern.

BACKGROUND AND OBJECTIVE: To investigate the burden and the financial and professional consequences for mothers and fathers after the onset of diabetes in their child in relationship to age at onset and family structure. PATIENTS AND METHODS: All families of children with an age at onset < 14 years and a diabetes duration < 10 years treated at four large pediatric diabetes centers received a structured questionnaire (burden of diabetes, professional position and career development, financial consequences for both parents, demographic data). RESULTS: 580 families with 583 children with type 1 diabetes (46 % girls, diabetes duration 5.0 +/- 3.2 years, age at onset 6.9 +/- 3.9 years) participated. 42 % of the children had an age at onset below 6 years. 11 % had single parents. Before the onset of diabetes in their children 93 % of the fathers worked full-time, thereafter 4 % changed their employment. Mothers worked at onset full-time in 22 % and part-time in 38 %; thereafter 31 % reduced their working time or stopped working. 33 % of the mothers reported handicaps in their professional career development, especially those with a child with age at onset below 6 years (44 %). Negative financial consequences were present in 44 % of the families. The day to day burden on a scale from 1 to 5 decreased both in mothers and in fathers with increasing age at onset. The individual burden was higher in mothers (3.6 +/-1.1) than in fathers (2.8 +/- 1.1) (p = 0.000). CONCLUSIONS: Initiatives to reduce the burden on families with a child with diabetes are urgently needed. Particularly the social and professional integration of mothers with younger children at diabetes onset need to be improved through support measures outside the family.