Matthias Grabert

Thyroid Autoimmunity in Children and Adolescents With Type 1 Diabetes: A multicenter survey

OBJECTIVE To investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Data were analyzed from 17,749 patients with type 1 diabetes aged 0.1-20 years who were treated in 118 pediatric diabetes centers in Germany and Austria. Antibodies to thyroglobulin (anti-TG) and thyroperoxidase (anti-TPO) were measured and documented at least once in 7,097 patients. A total of 49.5% of these patients were boys, the mean age was 12.4 years (range 0.3-20.0 years), and the mean duration of diabetes was 4.5 years (range 0.0-19.5 years). A titer exceeding 100 units/ml or 1:100 was considered significantly elevated. RESULTS In 1,530 patients, thyroid antibody levels were elevated on at least one occasion, whereas 5,567 were antibody-negative during the observation period. Patients with thyroid antibodies were significantly older (P < 0.001), had a longer duration of diabetes (P < 0.001), and developed diabetes later in life (P < 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P < 0.001). The prevalence of significant thyroid antibody titers increased with increasing age; the highest prevalence was in the 15- to 20-year age group (anti-TPO: 16.9%, P < 0.001; anti-TG: 12.8%, P < 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 microU/ml, range 0.0-615.0 microU/ml) than in control subjects (1.84 microU/ml, range 0.0-149.0 microU/ml) (P < 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 microU/ml, range 0.0-197.0 microU/ml). CONCLUSIONS Thyroid autoimmunity seems to be particularly common in girls with diabetes during the second decade of life and may be associated with elevated TSH levels, indicating subclinical hypothyroidism.

The ‘accelerator hypothesis’: relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus

Aims/hypothesisThe aim of this study was to investigate whether either increased weight or BMI are associated with the earlier manifestation of type 1 diabetes mellitus in children.MethodsWe evaluated anthropometric measurements in a large cohort of 9,248 patients of European extraction who were diagnosed in the years 1990–2003 in 116 pediatric clinics throughout Germany and Austria.ResultsPatients were divided into four groups according to age (0–4.9 years, 5–9.9 years, 10–14.9 years and 15–20 years). Significantly higher standard deviation scores (SDSs) for weight and BMI at diabetes onset were found for both boys and girls in the three younger age groups (up to 14.9 years of age) compared with the reference population (p<0.00001). In addition, the BMI SDS and the weight SDS were significantly higher in the 0–4.9-years age group than in all other groups (p<0.00001), and BMI SDS at onset gradually decreased with increasing age at manifestation (p<0.0001). Over the >10-year study period, there was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001), especially in the 5–9.9-years and the 10–14.9-years age groups. Multivariate analysis revealed a significant influence of male sex and of year of manifestation on BMI SDS (p<0.0001) and demonstrated a negative association between the patients’ BMI SDS and age at diagnosis, with a mean annual decrease in BMI SDS of −0.0248 (95% CI −0.0294 to −0.0202, p<0.0001).Conclusions/interpretationA higher BMI was associated with a younger age at diabetes onset. Increased weight gain could therefore be a risk factor for the early manifestation of type 1 diabetes.

Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database

Aims  To analyse and compare clinical characteristics in young patients with maturity‐onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM).

Thyroid Autoimmunity in Children and Adolescents with Type 1 Diabetes mellitus

Type 1 diabetes is often associated with additional autoimmune phenomena. However, data reported on the frequency of thyroid autoimmunity differ vastly. Therefore, the prevalence of thyroid autoantibodies was evaluated at a large pediatric diabetes center in Southern Germany. 2,305 determinations (TPO and TG, ELISA) were performed in 495 patients with type 1 diabetes (234 boys, 261 girls; age at last measurement: 15.4 ± 0.3 years, duration of diabetes 7.5 ± 0.2 years). The prevalence of elevated thyroid antibodies increased dramatically with age: from 3.7% in patients less than 5 years of age up to 25.3% in the age group 15–20 years (p < 0.0001). For children older than 10 years, girls were significantly more affected than boys (p < 0.0001). Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). In children older than 10 years, basal TSH concentrations were significantly elevated in antibody-positive patients (p < 0.05). In conclusion, thyroid autoimmunity is prevalent in children and adolescents with type 1 diabetes. Adolescent girls and young women are especially affected. Yearly routine determinations of thyroid antibodies are therefore recommended.

Diabetic retinopathy in pediatric patients with type-1 diabetes: Effect of diabetes duration, prepubertal and pubertal onset of diabetes, and metabolic control

OBJECTIVE The objective of this study was to determine the contribution of prepubertal and pubertal onset and duration of diabetes to the development of diabetic retinopathy. STUDY DESIGN A total of 1391 standardized fundus examinations (stereo fundus-photography) were performed in 441 children or adolescents with type-1 diabetes (median age 15.5 years, median duration of diabetes 6.3 years). RESULTS Mild nonproliferative retinopathy was present in 72 patients (median age 19.9 years). Life table analysis revealed a median duration of diabetes until retinopathy was first diagnosed at 16.6 years (95% confidence interval: 15.3 to 18.3). Patients were stratified according to diabetes onset before or in puberty (> or = 10.4 years in girls, > or = 12.2 years in boys). In children with a prepubertal onset of diabetes, retinopathy occurred after a pubertal duration of 10.9 years compared with 15.1 years in children with onset of diabetes in puberty (p < 0.01), demonstrating the additional risk conveyed by the prepubertal years of diabetes. Long-term metabolic control had a significant influence on the prevalence of retinopathy: patients with a median HbA1c > or = 7.5% had development of retinopathy on average after 15.5 years compared with 18.3 years in patients with lower HbA1c values (p < 0.05). CONCLUSION Both prepubertal and pubertal duration of diabetes are relevant for the development of background retinopathy. Good metabolic control should be attempted irrespective of age.

A framework for diabetes documentation and quality management in Germany: 10 years of experience with DPV

The DPV approach for quality management and documentation of diabetes in Germany consists of three basic modules: the diabetes documentation software DPV, semi-annual benchmarking for diabetes units (QC-DPV), and a data pool for diabetes research (DPV-SCIENT). The documentation system is available for general practices as well as for hospitals, and it supports the daily routine work of the diabetes team. The system covers a superset for all important data sets of quality initiatives in Germany. Longitudinal analyses of quality indicators related to diabetes are integrated. Twice a year, nation-wide benchmarking for pediatric diabetic units are performed, evaluating the outcome of their diabetes therapy. An improvement in completeness of control examinations could be observed during the last years in QC-DPV. The DPV-SCIENT data pool contains about 251000 single examinations of 21000 patients with diabetes. At least 53% of all patients with Type 1 diabetes in Germany who are less than 20 years of age are documented in DPV-SCIENT.

Arterial hypertension determined by ambulatory blood pressure profiles: contribution to microalbuminuria risk in a multicenter investigation in 2,105 children and adolescents with type 1 diabetes.

OBJECTIVE—Arterial hypertension is a key player in the development of diabetes complications. We used a nationwide database to study risk factors for abnormal 24-h blood pressure regulation and microalbuminuria in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Ambulatory blood pressure monitoring was performed in 2,105 children and adolescents from 195 pediatric diabetes centers in Germany and Austria. Individual least median squares (LMS)-SD scores were calculated for diurnal and nocturnal systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure according to normalized values of a reference population of 949 healthy German children. The nocturnal blood pressure reduction (dipping) was calculated for SBP as well as DBP. RESULTS—In diabetic children, nocturnal blood pressure in particular was significantly elevated (SBP +0.51, DBP +0.58, MAP +0.80 LMS-SD) and dipping of SBP DBP, and MAP was significantly reduced (P < 0.0001). Age, diabetes duration, sex BMI, A1C, and insulin dose were related to altered blood pressure profiles; dipping, however, was only affected by age, female sex, and A1C. The presence of microalbuminuria was associated with nocturnal DBP (P < 0.0001) and diastolic dipping (P < 0.01). CONCLUSIONS—Our observations revealed a clear link between the quality of metabolic control and altered blood pressure regulation even in pediatric patients with short diabetes duration. Nocturnal blood pressure in particular seems to mainly contribute to diabetes complications such as microalbuminuria.

Diabetes mellitus type 2 in childhood and adolescence in Germany and parts of Austria

A rise in the prevalence of type 2 diabetes mellitus (T2 DM) in adolescence and childhood has been observed in North America, especially in minority populations such as the American Indians, during the past decades [2]. Few epidemiological data on the incidence of the disease in young people exist in Europe [1, 4, 5]. To obtain an estimate of the magnitude of this problem in Germany, we tried to evaluate the prevalence of T2 DM in people under the age of 20 years using the DPV-Wiss database, a database covering half of the existing diabetes patients in this age group in Germany.

Screening frequency for celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus – data from a German/Austrian multicentre survey

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.

Indications for insulin pump therapy in different age groups- : an analysis of 1567 children and adolescents

Aims  The German working group for pump therapy in paediatric patients has defined seven indications for continuous subcutaneous insulin infusion (CSII): dawn phenomenon, reduction of severe hypoglycaemia, improvement of hyperglycaemia, more flexibility, motivation, failure of injection therapy and pregnancy. In this study we analysed age‐specific differences for starting CSII in four age groups (group A: 0–4 years; group B: 5–9 years; group C: 10–14 years; group D: 15–19 years). We also investigated whether glycaemic goals could be reached.