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

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.

Keywords: C-X-C motif chemokine 10; Glutamic decarboxylase-65; Type 1 diabetes.