GAD treatment and insulin secretion in recent-onset type 1 diabetes.

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. METHODS: We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 microg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. RESULTS: Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (-0.21 vs. -0.27 nmol per liter [-0.62 vs. -0.81 ng per milliliter], P=0.045), as did stimulated secretion measured as the area under the curve (-0.72 vs. -1.02 nmol per liter per 2 hours [-2.20 vs. -3.08 ng per milliliter per 2 hours], P=0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. CONCLUSIONS: GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)

Persistent effects of a pedagogical device targeted at prevention of severe hypoglycaemia: a randomized, controlled study.

AIM: To study the long-term use of self-study material in type 1 diabetes patient education targeted at the prevention of severe hypoglycaemia. METHODS: Randomized 1:1:1 control study in three local hospitals. We studied 332 type 1 diabetes patients from the geographic population, aged 2.6-18.9 y at entry. The intervention group received a videotape and brochure in which interviewed patients, parents and medical experts reviewed in detail practical skills for self-control and treatment, with the aim of preventing severe hypoglycaemia. There were two control groups: one received a videotape and brochure with general diabetes information and the other only traditional treatment. Primary endpoints were severe hypoglycaemia needing assistance by another person and HbA1c. Dissemination, reading/viewing level, patients' attitudes and extra contact with caregivers were also investigated. At 24 mo, 249 subjects provided data. RESULTS: The yearly incidence of severe hypoglycaemia decreased at 24 mo from 42% to 25% (difference 17%, 95% CI 3-31, p = 0.0241) in the intervention group, but not in controls. HbA1c remained unchanged. Video use during months 13-24 was higher in the intervention group than in controls (p = 0.0477), ranging from 1-15 (median 2) times, among 37% of patients (months 1-12, 100%). Higher future use was anticipated for intervention material (p = 0.0003). Extra caregiver contact was related to severe hypoglycaemia (p = 0.0009). The cost of the material was

Use of the Internet to search for information in type 1 diabetes children and adolescents: a cross-sectional study.

We have studied use of the Internet in search for diabetes-related information in a geographic population of type 1 diabetes children and adolescents. Using a randomised cross-sectional design, 90 out of 110 patients aged 5-20 years responded to a postal questionnaire. Thirty-eight subjects (42%) had searched for diabetes information on the Internet, at a median of 3 occasions, range 1-50. Out of the searching families, 32% had also shown diabetes information from the Internet to others, such as relatives, friends and school staff. Eighty-six percent had found information in Swedish, 32% in English and 68% indicated a need for more information in Swedish. 97% percent anticipated future use. Specific web-sites were suggested by 24%. Searchers as compared to non-searchers had a shorter diabetes duration (p = 0.0255) and more recent extra contacts with their caregivers (p = 0.0018). We conclude that Internet-based information and support may be requested at a high extent by patients, as a complement to regular visits to the diabetes team and other types of traditional care and education. The results suggest a great need for development of systems combining technical and human support, which is discussed. The findings may also have implications for other topics within diabetes education, other ages, and for other diagnosis groups.

Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes.

OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.

Symptoms and signs have changed in Swedish children with coeliac disease.

OBJECTIVE: To examine symptoms and signs in children with coeliac disease and determine whether the clinical picture at disease onset has changed as incidence of the disease has decreased in the last 10 years. This project was part of the ABIS study (All Babies in Southeast Sweden, born from October 1997 to October 1999). METHODS: Eight paediatric departments in Southeast Sweden recorded all children with coeliac disease and registered symptoms according to a standard form. Data were obtained from 79 children with biopsy-confirmed coeliac disease, 43 contemporary controls, and 65 historic controls. RESULTS: When compared with children with normal intestinal biopsies, children with coeliac disease more often had abdominal distension (odds ratio [OR] = 22.17; 95% confidence interval [CI] OR = 5.00-98.25), thin extremities (OR = 5.89; 95% CI OR = 2.09-16.55), irritability (OR = 6.50; 95% CI OR = 1.83-23.03), and tiredness (OR = 15.43; 95% CI OR = 2.00-119.16). When compared with coeliac children diagnosed at < or =2 years of age in Gothenburg between 1985 and 1989, when the incidence of coeliac disease was three times higher, ABIS patients aged < or =2 years at diagnosis had less often experienced diarrhoea (OR = 0.23; 95% CI OR = 0.12-0.65), suboptimal weight gain (OR = 0.02; 95% CI OR = 0.01-0.10), or suboptimal linear growth (OR = 0.14; 95% CI OR = 0.05-0.39). CONCLUSION: This study indicates that, in parallel to changes in incidence, clinical features of coeliac disease in young children have changed during the last 10 years.

Indwelling catheters used from the onset of diabetes decrease injection pain and pre-injection anxiety.

OBJECTIVES: To investigate the use of indwelling catheters as injection aids at diabetes onset to reduce injection pain and pre-injection anxiety. STUDY DESIGN: Forty-one patients aged 8.1 +/- 3.7 years (range, 1-15) participated in this open, controlled randomized study. A 10-cm VAS with faces was used for scoring. A local anesthetic cream was used before all insertions. The control group used insulin pens with standard needles. After one week, the indwelling catheter group could choose regular injections but were included in the "intention to treat" analysis. RESULTS: Injection pain and anxiety decreased from day 1 to 15 in both groups (average, 4.1 injections/day). Pain was significantly lower for indwelling catheter injections when scored by parents (median, 1.2 cm vs 2.7 cm; P =.002), children/teenagers (0.8 cm vs 1.5 cm; P =.006), and nurses (1.4 cm vs 3.0 cm; P =.002). Parental pre-injection anxiety was also lower (1.2 cm vs 2.9 cm; P =.016). Taking injections, including inserting catheters, was found to be less problematic with an indwelling catheter (1.6 cm vs 3.3 cm;P =.009). During the 6-month follow-up, injection pain and injection problems were significantly lower in the catheter group. Mean catheter indwelling time was 3.7 days. Median pain for catheter insertion was 2.1 cm and for glucose testing was 0.9 cm. Sixteen of 20 patients continued to use indwelling catheters after 2 weeks, and 9 of 20 after 6 months. CONCLUSIONS: We found an evident relief of pre-injection anxiety and injection pain when using indwelling catheters for introducing insulin injections at the onset of diabetes.