Journal of Diabetes Investigation (Nov 2019)

Circulating anti‐glutamic acid decarboxylase‐65 antibody titers are positively associated with the capacity of insulin secretion in acute‐onset type 1 diabetes with short duration in a Japanese population

  • So Yamamura,
  • Tomoyasu Fukui,
  • Yusaku Mori,
  • Toshiyuki Hayashi,
  • Takeshi Yamamoto,
  • Makoto Ohara,
  • Ayako Fukase,
  • Hiroto Sasamori,
  • Tetsuro Kobayashi,
  • Tsutomu Hirano

DOI
https://doi.org/10.1111/jdi.13052
Journal volume & issue
Vol. 10, no. 6
pp. 1480 – 1489

Abstract

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Abstract Aims/Introduction To elucidate the relationship between titers of islet autoantibodies, the C‐X‐C motif chemokine 10 – a circulating chemokine that activates T‐helper 1 cells leading to β‐cell destruction – and β‐cell function in type 1 diabetes. Materials and Methods In total, 58 type 1 diabetes patients positive for glutamic decarboxylase‐65 autoantibodies (GADA)‐radioimmunoassay (mean age 54.1 years; 27 acute‐onset cases and 31 slowly progressive cases) were enrolled; serum C‐X‐C motif chemokine 10 (n = 50), zinc transporter 8 autoantibodies (n = 50) and GADA (n = 58) by an enzyme‐linked immunosorbent assay, and insulinoma‐associated antigen‐2 autoantibodies by radioimmunoassay (n = 50) were measured. The ratio of 100 × random C‐peptide (ng/mL)‐to‐plasma glucose levels (mg/dL; C‐peptide index [CPI]) was measured. Results The CPI significantly decreased in both groups with the progression of disease duration. GADA titers by radioimmunoassay and enzyme‐linked immunosorbent assay were strongly correlated with the CPI in acute‐onset type 1 diabetes patients with a shorter disease duration (≤10 years), but not in those with a longer duration or slowly progressive type 1 diabetes. Neither insulinoma‐associated antigen‐2 nor zinc transporter 8 autoantibodies titers were correlated with the CPI. Serum C‐X‐C motif chemokine 10 levels in both groups were significantly higher than in non‐diabetic controls, and persisted at high levels even in those with chronic duration. Conclusions Among islet autoantibodies, the intensity of the humoral immune response, as defined by GADA titers, reflected the degree of residual β‐cell function in acute‐onset type 1 diabetes patients with short duration. Prolonged disease activity might accelerate β‐cell impairment in both subtypes of type 1 diabetes.

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