GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

Diabetes and neurodegeneration in Wolfram syndrome: a multicenter study of phenotype and genotype.

OBJECTIVE: To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation. RESEARCH DESIGN AND METHODS: The clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes. RESULTS: WSD was diagnosed earlier than type 1 diabetes (5.4±3.8 vs. 7.9±4.2 years; P<0.001) with a lower prevalence of ketoacidosis (7 vs. 20%; P=0.049). Mean duration of remission in WSD was 2.3±2.4 vs. 1.6±2.1 in type 1 diabetes (NS). Severe hypoglycemia occurred in 37 vs. 7.9% (P<0.001). Neurologic disease progression was faster in the WSD group with a mean HbA1c>7.5% (P=0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P=0.028). CONCLUSIONS: Endoplasmic reticulum stress-mediated decline of ß-cells in WSD occurs earlier in life than autoimmune-mediated ß-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease.

[Application of standardized patients in teaching, learning and assessment]. / Einsatz von Simulationspatienten als Lehr-, Lern- und Prüfungsform.

The new German requirements for Licensure to practice medicine focus on teaching clinical skills. It will become difficult for Medical Schools to fulfil these new requirements in the training of medical students with the increasing cost effectiveness in patient care. Standardized patients can be a very useful tool in teaching clinical skills. Implementation of a standardized patients program provides a quasi-real but safe learning environment in which students can acquire skills in physical examination, history taking, interpersonal and communication skills. These skills can also be assessed in this environment.

First year medical students' perceptions of stress and support: a comparison between reformed and traditional track curricula.

BACKGROUND: The authors hypothesised that medical schools need to support their students by identifying the challenges inherent in the demanding study of medicine, especially during the transitional phase at the beginning of study. Therefore, a study was conducted to evaluate Year 1 students' perceptions on how well 2 different programmes--a reformed and a traditional programme--helped students make a good start to their studies. DESIGN: Cross-sectional survey. METHOD AND PARTICIPANTS: A questionnaire was distributed to Year 1 medical students on reformed (RT) and traditional track (TT) curricula. Its 5 subscales measured perceived stress and support. RESULT: A total of 155 students (70% of the year group) responded. Significant differences between groups appeared in 4 of the 5 subscales. Students on the RT felt more supported than students on the TT in terms of study conditions, social support at university, perceptions of their own attitudes and competencies, and living conditions. No differences in perceptions of social support outside university were apparent. CONCLUSION: Key aspects that were perceived as supportive included good contact with fellow students and teachers, high quality of courses, and a curriculum that fulfilled students' expectations and made sense to them. In identifying particular features that led to the positive judgement of the RT, the authors hypothesised that the following aspects were crucial: the specific orientation unit in the first 2 weeks, the problem-based learning workshop, the coursebooks and extracurricular social activities.