Angelika Thon

β-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?

Background: In adults, a fraction of diabetic individuals with β-cell autoantibodies has initially non-insulin requiring diabetes clinically appearing as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood (LADA). The occurrence of β-cell autoantibodies in European children and adolescents with T2DM has not been reported so far. Methods: The frequency of β-cell autoantibodies (anti-GAD, anti-IA-2, and anti-ICA) was determined in 7050 diabetic children and adolescents. The type of diabetes was classified by paediatric diabetic specialists based on the clinical presentation. Children with non-insulin dependent T2DM over a one year period were studied separately. Results: A total of 6922 children were clinically classified as having type 1 diabetes (T1DM) and 128 children as having T2DM. Thirty six per cent of the children with T2DM had at least one detectable β-cell autoantibody. These children did not differ significantly from the children with T2DM and without autoantibodies in respect of age, gender, weight status, lipids, blood pressure, C-peptide, glucose, and HbA1c at manifestation, as well as frequency of anti-thyroidal antibodies and insulin treatment during follow up. In the subgroup of the 38 children with T2DM without insulin requirement over a one year period, autoantibodies occurred in 32%. These 12 children were predominantly obese (67%), female (67%), and in the pubertal age range. Conclusion: β-cell autoantibodies were detectable in a subgroup of initially non-insulin dependent diabetic children and adolescents with the clinical appearance of T2DM. Following the terminology “latent autoimmune diabetes in adulthood (LADA)”, this subgroup might be classified as “LADY” (latent autoimmune diabetes in youth).

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).

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.

Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis

OBJECTIVES Etanercept, a recombinant TNF receptor fusion protein, has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years. In adult patients, efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly. Therefore, safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c. was evaluated in a 3 month open label trial. METHODS Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial. Active polyarticular disease was defined by the presence of five or more active joints with swelling, alternatively with pain or tenderness combined with limitation of motion. Safety assessments were based on adverse events (AEs) reports. Efficacy was assessed using the PedACR30/50/70 criteria. RESULTS At the start of treatment the patients showed high disease activity. A rapid reduction of all disease activity parameters was observed. A PedACR30/50/70 response was reached by 75%/35%/10% of patients after 4 weeks, 90%/75%/35% after 8 weeks and 95%/75%/75% after 12 weeks of treatment. There were 37 AEs, none of them serious, with injection site reactions and minor infections being the most frequent. There was no drop out. Long-term follow-up of the patients will be carried out in the German JIA Registry. CONCLUSION Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated.

Polyendocrinopathy in Children, Adolescents, and Young Adults With Type 1 Diabetes A multicenter analysis of 28,671 patients from the German/Austrian DPV-Wiss database

OBJECTIVE To investigate diabetes-specific autoantibodies and additional autoimmune phenomena in a large cohort of young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Data from 28,671 patients <30 years with type 1 diabetes from 242 specialized centers in Germany and Austria were analyzed. RESULTS At least one β-cell antibody was present in 81.6% of patients. β-cell–Ab-negative patients were significantly younger at diabetes onset (P < 0.0001). A total of 19.6% had positive thyroid antibodies with female predominance (62%, P < 0.0001). Antibodies to tissue transglutaminase were present in 10.7%, with a significantly longer duration of diabetes (P < 0.0001). Parietal cell antibodies were found in 283 patients, associated with older age (P < 0.001), and adrenal antibodies were present in 94 patients. In 575 patients, at least three different autoimmune phenomena were present. CONCLUSIONS Thyroid autoimmunity and antibodies suggestive for celiac disease are the most prevalent additional immune phenomena in type 1 diabetes. Parietal/adrenal antibodies are rare.

Entities and frequency of neonatal diabetes: data from the diabetes documentation and quality management system (DPV)

Diabet. Med. 27, 709–712 (2010)

Improvement in health-related quality of life for children with juvenile idiopathic arthritis after start of treatment with etanercept.

Improvement in health‐related quality of life (HRQOL) is an important therapy goal in the treatment of patients with juvenile idiopathic arthritis (JIA). We investigated the 12‐month course of HRQOL in patients with JIA after the start of therapy with etanercept and identified its determining factors.

Diagnosis of paediatric Lyme arthritis using a clinical score.

Abstract Diagnosis of Lyme arthritis (LA) in children and adolescents may be difficult due to non-specific clinical manifestations and unreliable serological tests for antibodies to Borrelia burgdorferi. In a national prospective study, 186 children with arthritis were examined in whom the attending physicians had considered the diagnosis of LA. Ultimately, LA was confirmed in 87 patients and these were compared with the remaining 99 children in whom arthritis was attributable to other causes. In comparison to patients with other causes of arthritis, patients with LA had a higher frequency of episodic arthritis and initial knee joint arthritis, reported tick bites more frequently, were older, had a lower frequency of initial arthralgias, and there were fewer large joints involved. A score was developed in a group of these patients and tested in a second group. It enabled patients with LA to be distinguished from those with other causes of arthritis: within a range from 12 to −7 points, a score of 2.5 or less excluded LA whereas 6 or more points were highly indicative of LA. If only those children with a score result between 2.5 and 6 had been tested for antibodies to B. burgdorferi, the number of tests would have been reduced by 63%. Conclusion Careful analysis of clinical presentation and use of a clinical score may help in distinguishing LA from other causes of arthritis and thus reduce unnecessary and expensive testing and uninterpretable test results.

Distinct Effects of Methotrexate and Etanercept on the B Cell Compartment in Patients With Juvenile Idiopathic Arthritis

B cells have been shown to play an important role in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Current treatments include the disease‐modifying antirheumatic drugs methotrexate (MTX) and tumor necrosis factor α inhibition with etanercept. This study was undertaken to determine how these drugs influence the B cell compartment in patients with JIA.

Pharmacokinetics of Meloxicam in Patients With Juvenile Rheumatoid Arthritis

The pharmacokinetics of a meloxicam suspension were studied in 18 children with juvenile rheumatoid arthritis. Children received a single 0.25‐mg/kg dose up to a maximum of 15 mg. Pharmacokinetic parameters after the first dose were calculated by noncompartmental methods. Geometric mean (percent coefficient of variation for geometric mean [gCV]) Cmax, AUC0‐∞, apparent clearance, apparent volume of distribution, and elimination half‐life values were 1.24 μg/mL (47% gCV), 25.6 μg•h/mL (81% gCV), 0.17 mL/min/kg (83% gCV), 0.19 L/kg (63% gCV), and 13.4 hours (54% gCV) in the younger group and 1.89 μg/mL (25% gCV), 35.8 μg•h/mL (21% gCV), 0.12 mL/min/kg (23% gCV), 0.13 L/kg (22% gCV), and 12.7 hours (21% gCV) for the older group, respectively. Area under the curve, volume of distribution, and clearance tended to be higher in the younger group, whereas elimination half‐lives were similar. A post hoc comparison to pharmacokinetic data in adults revealed no relevant differences. Thus, a common body weight–normalized dose is considered appropriate for children older than 2 years.