Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study
Our aim was to evaluate insulin autoantibody (IAA) levels over time in the Diabetes Prevention Trial Type 1 (DPT-1) oral insulin study to determine the effect of oral insulin compared with placebo on IAA levels.
Subjects and methods
The DPT-1 trial randomised 372 relatives of subjects with type 1 diabetes, positive for IAA and with normal IVGTTs and OGTTs, to oral insulin 7.5 mg daily or placebo. Subjects were followed with IVGTTs, OGTTs and serial IAA measurements. The change in IAA level over time was modelled statistically using mixed model longitudinal data analysis with spatial exponential law for unevenly spaced data. In a separate analysis, subjects were divided into four groups by treatment and diabetes status at the end of the study. IAA levels were compared amongst the groups at randomisation, last sampling and at the maximum level.
Longitudinal data analysis showed that treatment did not affect levels of IAA over time. After controlling for age, the IAA levels at randomisation and the last visit and the maximum values were different in the four groups. Significantly higher levels were noted in groups that developed diabetes compared with those that did not, with no significant difference by treatment group.
This suggests that IAA levels over time were not influenced by oral insulin in subjects already positive for IAA at the start of treatment.
ClinicalTrials.gov ID no.: NCT00004984.
- Diabetes Prevention Trial Type 1 Study Group (2005) Effects of oral insulin in relatives of patients with type 1 diabetes: the Diabetes Prevention Trial-Type 1. Diabetes Care 28:1068–1076 CrossRef
- Lauritano AA, Clements RS Jr, Bell D (1989) Insulin antibodies in non-insulin-dependent diabetes mellitus: effect of treatment with semisynthetic human insulin. Clin Ther 11:268–277
- Diabetes Prevention Trial Type 1 Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691 CrossRef
- Vardi P, Dib SA, Tuttleman M et al (1987) Competitive insulin autoantibody assay. Prospective evaluation of subjects at high risk for development of type 1 diabetes mellitus. Diabetes 36:1286–1291 CrossRef
- Jones RH (1993) Longitudinal data with serial correlation: a state-space approach. Monogr Stat Appl Probab 47:25–76
- Achenbach P, Warncke K, Reiter J et al (2004) Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. Diabetes 53:384–392 CrossRef
- Hoppu S, Ronkainen MS, Kimpimaki T et al (2004) Insulin autoantibody isotypes during the prediabetic process in young children with increased genetic risk of type 1 diabetes. Pediatr Res 55:236–242 CrossRef
- Achenbach P, Koczwara K, Knopff A, Naserke H, Ziegler AG, Bonifacio E (2004) Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes. J Clin Invest 114:589–597 CrossRef
- Achenbach P, Warncke K, Reiter J et al (2006) Type 1 diabetes risk assessment: improvement by follow-up measurements in young islet autoantibody-positive relatives. Diabetologia 49:2969–2976 CrossRef
- van de Linde P, Roep BO (2005) T-cell assays to determine disease activity and clinical efficacy of immune therapy in type 1 diabetes. Am J Ther 12:573–579 CrossRef
- Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study
Volume 50, Issue 8 , pp 1603-1606
- Cover Date
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- Insulin autoantibodies
- Oral insulin
- Type 1 diabetes
- Industry Sectors
- Author Affiliations
- 1. Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO, USA
- 3. Barbara Davis Center for Childhood Diabetes, Box A140, Building M20, 1775 N. Ursula Street, P.O. Box 6511, Aurora, CO, 80045-6511, USA
- 2. Joslin Diabetes Center, Boston, MA, USA