Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

Diabetologia. 1997 May;40(5):564-72. doi: 10.1007/s001250050716.


Insulin-dependent diabetes mellitus (IDDM) is the result of a T-cell mediated autoimmune beta-cell destruction, which is accompanied by autoantibodies. We analysed the cellular and humoral immune response to insulin and insulin peptides in patients with recent-onset IDDM, IDDM patients treated with insulin, non-diabetic first degree relatives and unrelated control subjects. There were no differences in T-cell reactivity to whole insulin or insulin peptides in general between age-matched groups of IDDM patients, relatives or healthy control subjects. In contrast to investigations in NOD mice, no immunodominant or disease-specific insulin peptide could be identified. Surprisingly, a positive correlation of T-cell responses to insulin with age was noticed (p < 0.005). This resulted in an inverse relation of insulin autoantibodies (IAA) and insulin reactive T-cells (p < 0.001) together with the well-described negative correlation of IAA with age. Interestingly, insulin-treated patients differed from age-matched recent-onset IDDM patients: first, simultaneous immune recognition of insulin with T-cells and IAA was only seen in patients treated for 6 months with insulin; second, insulin-treated patients rarely responded to whole insulin; third, they displayed less determinant spreading, and finally, recognition of multiple insulin peptides was not accompanied by crossreactivity to whole insulin. These distinct observations in insulin-treated IDDM patients, together with the inverse correlation between humoral and cellular responses to insulin, may result from activation or modulation of different T-cell subsets, and may be of relevance to insulin therapy trials, in which selective activation of non-destructive T-cell subsets may be a key to successful intervention.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Autoantibodies / blood*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Conserved Sequence
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Family
  • Female
  • HLA-DQ Antigens / analysis
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • Humans
  • Insulin / immunology*
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Insulin Antibodies / blood*
  • Islets of Langerhans / immunology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred NOD
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Reference Values
  • Risk Assessment
  • T-Lymphocytes / immunology
  • Time Factors


  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • Insulin
  • Insulin Antibodies
  • Peptide Fragments
  • Recombinant Proteins
  • islet cell antibody