Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus

Diabet Med. 1998 Oct;15(10):844-50. doi: 10.1002/(SICI)1096-9136(199810)15:10<844::AID-DIA679>3.0.CO;2-A.

Abstract

Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c <6% and insulin <0.3 U kg(-1) day(-1)) occurred in 22/192 (11%) patients at 3 months of follow-up, in 15/190 (8%) patients at 6 months and in 8/169 (5%) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Antibody Specificity / immunology
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / metabolism
  • HLA-DR Antigens / immunology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Infant
  • Insulin / immunology
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Insulin Secretion
  • Islets of Langerhans / immunology
  • Islets of Langerhans / metabolism*
  • Male
  • Membrane Glycoproteins / immunology
  • Membrane Proteins*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / immunology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Remission, Spontaneous
  • Retrospective Studies

Substances

  • Autoantibodies
  • Autoantigens
  • Glycated Hemoglobin A
  • HLA-DR Antigens
  • Hypoglycemic Agents
  • Insulin
  • Membrane Glycoproteins
  • Membrane Proteins
  • C-Reactive Protein
  • PTPRN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase