Objective: We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults (LADA).

Methods: This multicenter, randomized, non-blinded clinical study screened 4,089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin requiring diabetic patients with =/< 5-year duration of diabetes were assigned to either SU group (n = 30) or Insulin group (n = 30). Serum C-peptide responses to annual OGTTs were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during OGTT (sigma C-peptide) <4 ng/ml (1.32 nmol/l).

Results: The progression rate to an insulin-dependent state in Insulin group (3/30, 10%) was lower than that in SU group (13/30, 43%; p = 0.003, log-rank). Longitudinal analysis demonstrated that sigma C-peptide values were better preserved in Insulin group than in SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers (=/> 10 U/ml: 180 WHO U/ml) and preserved beta-cell function (sigma C-peptide =/> 10 ng/ml [3.31 nmol/l]) at entry. No severe hypoglycemic episodes occurred during the study.

Conclusions: Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM/LADA.