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


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.
Murao
Satoshi
S
Matsuyama Shimin Hospital, Ehime, Japan.
Kondo
Shiori
S
Ohashi
Jun
J
Fujii
Yasuhisa
Y
Shimizu
Ikki
I
Fujiyama
Masao
M
Ohno
Keizo
K
Takada
Yasuharu
Y
Nakai
Kazuaki
K
Yamane
Yukio
Y
Osawa
Haruhiko
H
Makino
Hideichi
H
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002096:C-Peptide / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007453:Iodide Peroxidase / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors
D001323:Autoantibodies; D015415:Biomarkers; D002096:C-Peptide; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C096322:ICA512 autoantibody; D007328:Insulin; D007453:Iodide Peroxidase