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.)

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.