Anti-thyroid peroxidase antibody, IA-2 antibody, and fasting C-peptide levels predict beta cell failure in patients with latent autoimmune diabetes in adults (LADA)--a 5-year follow-up of the Ehime study

Diabetes Res Clin Pract. 2008 Apr;80(1):114-21. doi: 10.1016/j.diabres.2008.01.024. Epub 2008 Mar 14.


Objective: To clarify the natural course and factors involved in beta cell failure in Japanese latent autoimmune diabetes in adults (LADA) patients.

Research design and methods: Insulin secretion in 57 LADA patients identified from among 4980 adult-onset diabetic patients in a hospital-based Ehime study were examined over a 5-year period. Postprandial serum C-peptide levels below 0.33 nmol/l were defined as beta cell failure. The involvement of clinical and immunological factors in the progression to beta cell failure were evaluated.

Results: Forty-two of the fifty-seven LADA patients completed the 5-year follow-up. Eleven (26.2%) required insulin treatment and five (11.9%) progressed to beta cell failure. A Cox regression analysis revealed that positive anti-thyroid peroxidase antibody (TPOAb) and insulinoma-associated protein 2 (IA-2Ab) were associated with the need for insulin treatment (p<0.05 and p<0.01, respectively). Positive TPOAb, anti-thyroglobulin antibody (TGAb), IA-2 antibody (p<0.01 for each), and lower serum fasting C-peptide levels (p<0.05) were contributors to the progression to beta cell failure. Involvement of type 1 diabetes susceptible HLA class II genes was not evident.

Conclusions: Japanese LADA patients are a heterogeneous population. In addition to IA-2 antibody, presence of TPOAb and fasting C-peptide level could indicate an oncoming deterioration of beta cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Asian Continental Ancestry Group / statistics & numerical data
  • Autoantibodies / blood*
  • Biomarkers / blood*
  • C-Peptide / blood*
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / epidemiology
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Haplotypes
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Iodide Peroxidase / immunology*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors


  • Autoantibodies
  • Biomarkers
  • C-Peptide
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • ICA512 autoantibody
  • Insulin
  • Iodide Peroxidase