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 Ͻ 0.001), had a longer duration of diabetes (P Ͻ 0.001), and developed diabetes later in life (P Ͻ 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 Ͻ 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 Ͻ 0.001; anti-TG: 12.8%, P Ͻ 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 U/ml, range 0.0 -615.0 U/ml) than in control subjects (1.84 U/ml, range 0.0 -149.0 U/ml) (P Ͻ 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 U/ml, range 0.0 -197.0 U/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.

On the basis of the positive outcome of animal experiments, several large placebo-controlled trials are underway and aiming for the first time at the prevention of an immune-mediated disease, type 1 diabetes. The first of these trials, The Deutsche Nicotinamide Intervention Study (DENIS), evaluated the clinical efficacy of high doses of nicotinamide in children at high risk for IDDM. Nicotinamide has been shown to protect beta-cells from inflammatory insults and to improve residual beta-cell function in patients after onset of IDDM. Individuals at high risk for developing IDDM within 3 years were identified by screening the siblings (age 3-12 years) of patients with IDDM for the presence of high titer (> or =20 Juvenile Diabetes Foundation [JDF] U) islet cell antibodies. Probands (n = 55) were randomized into placebo and nicotinamide (slow release, 1.2 g x m(-2) x day(-1)) receiving groups and followed prospectively in a controlled clinical trial using a sequential design. Rates of diabetes onset were similar in both groups throughout the observation period (maximum 3.8 years, median 2.1 years). This sequential design provides a 10% probability of a type II error against a reduction of the cumulative diabetes incidence at 3 years from 30 to 6% by nicotinamide. The trial was terminated when the second sequential interim analysis after the eleventh case of diabetes showed that the trial had failed to detect a reduction of the cumulative diabetes incidence at 3 years from 30 to 6% (P = 0.97). The group receiving nicotinamide exhibited decreased first-phase insulin secretion in response to intravenous glucose (P = 0.03). No other side effects were observed. We conclude that in this subgroup of diabetes-prone individuals at very high risk and with an assumed rapid disease progression, nicotinamide treatment did not cause a major decrease or delay of diabetes development. However, the data do not exclude the possibility of a less strong, but potentially meaningful, risk reduction in this cohort, or a major clinical effect of nicotinamide in individuals with less risk of progression to IDDM than studied here.

Our case proves that an aggressive treatment should be undertaken and can be successful in CNS pseudallescheriasis.

In this study in euthyroid patients with AIT and T1D, l-T(4) treatment reduced thyroid volume but had no effect on thyroid function and serum autoantibody levels.

Objective: We investigated whether or not serum levels of the soluble leptin receptor (sOB-R) and leptin are related to anthropometric and metabolic changes during pubertal development of children and adolescents with type 1 diabetes mellitus. Design and methods: Blood levels of sOB-R, leptin and HbA1C, as well as body-mass index (BMI), diabetes duration and daily insulin doses, were determined in 212 (97 girls; 115 boys) children with type 1 diabetes mellitus and compared with the sOB-R serum levels in 526 healthy children and adolescents. Results: OB-R serum levels and parallel values of the molar ratio between sOB-R and leptin were significantly higher in children with diabetes than in normal children (P , 0.05) in almost all investigated Tanner stages. Furthermore, in the entire group of patients, we demonstrated statistically significant correlations (P , 0.02) between sOB-R and the duration of diabetes (r ¼ 0.30), HbA1c levels (r ¼ 0.32) and the insulin dose (r ¼ 0.18). Multiple-regression analysis revealed that HbA1c (12.4%), height (7.9%) and duration of diabetes (8.7%) contributed to 29% variance of sOB-R in diabetic children. Conclusions: Our data suggest that poor glycemic control in diabetes may lead to increased serum levels of sOB-R. This regulation of sOB-R appears to be independent of leptin, but may have an impact on leptin action. The consequently developing molar excess of sOB-R related to leptin could reduce leptin sensitivity and may, therefore, influence leptin-related anthropometric and metabolic abnormalities.European Journal of Endocrinology 151 475-481