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Factors affecting insulin antibody binding in children with insulin-dependent diabetes mellitus
D Daneman1, L Fishman, C Clarson
1Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Newly diagnosed patients with insulin-dependent diabetes mellitus (IDDM) show high insulin antibody binding before therapy, which increases over time. This binding is unrelated to metabolic control or free insulin levels post-therapy.
Area of Science:
- Endocrinology
- Immunology
- Pediatrics
Background:
- Insulin antibody binding is a known phenomenon in type 1 diabetes.
- Previous studies suggest elevated insulin antibody levels in newly diagnosed patients.
Purpose of the Study:
- To investigate insulin antibody binding in children with newly diagnosed and long-standing insulin-dependent diabetes mellitus (IDDM).
- To determine the relationship between pre-treatment antibody binding and later levels.
- To assess the correlation between antibody binding, metabolic control, and free insulin levels.
Main Methods:
- Study 1: Measured insulin antibody binding in 32 children with new-onset IDDM before and up to 6 months after insulin therapy.
- Study 2: Measured insulin antibody binding and free insulin levels in 35 children with long-standing IDDM following insulin injection.
Main Results:
- Nearly 35% of new-onset IDDM subjects had elevated insulin antibody binding pre-treatment.
- Antibody binding significantly increased over 6 months of therapy in prospective subjects.
- Pre-treatment binding did not correlate with later binding or metabolic control.
- In long-standing IDDM, antibody binding was not related to metabolic control or the rate of free insulin rise.
Conclusions:
- Confirmed elevated insulin antibody binding in pre-treatment children with IDDM.
- No clear relationship was found between pre-treatment binding and binding 6 months post-therapy.
- Insulin antibody binding in established IDDM is independent of metabolic control and insulin absorption dynamics.
Abstract:
We measured insulin antibody binding in 2 groups of patients: Study 1, 32 children with newly diagnosed IDDM before onset of insulin therapy, and, in 20 of these, 10 days, 1, 3, and 6 months after beginning therapy; and Study 2, 35 children with long-standing IDDM, 20 of whom had free insulin concentrations measured before, and for 2 hours following subcutaneous injection of 0.25 U/kg regular insulin. Almost 35% of new onset subjects had insulin antibody binding above control levels. In those studied prospectively, binding increased significantly with time. Pre-treatment binding did not correlate with later insulin antibody binding nor metabolic control. In Study 1 we have confirmed previous studies showing abnormally high insulin antibody binding in children with IDDM pre-treatment. We have been unable to demonstrate a relationship between this binding and that found 6 months after initiation of therapy. In Study 2, we have shown that insulin antibody binding is not related to either the level of metabolic control or the rate of rise of free insulin levels in children with IDDM.