Heterogeneity among patients with latent autoimmune diabetes in adults

Background: Some type 1 diabetic patients do not require insulin at diagnosis of diabetes, and they progress to insulin dependence only after several years (latent autoimmune diabetes in adults). However, not all patients with latent autoimmune diabetes in adults progress to insulin dependence. We compared the characteristics of patients with high glutamic acid decarboxylase antibodies (GADA) titres (≥10 U/mL) to those of patients with low titres and examined other factors possibly associated with the progression to insulin dependence. Methods: We began registering diabetic patients in 1993 and have since followed them prospectively. Among these patients, we analysed clinical characteristics and progression to insulin dependence in those followed for more than 5 years. Results: Patients with high GADA titres were younger and had lower body mass index, shorter disease durations and lower serum C-peptide (s-CPR) levels than the patients with low GADA titre and GADA negative type 2 diabetes. Frequencies of other islet-related autoantibodies were significantly higher in patients with high GADA titre than in those with low GADA titres. Disease protective HLA class II genotypes were less frequent in patients with high titre. The positive predictive value of being GADA positive was only 42.7%. The positive predictive value increased to 78.6% when the cut-off was set at the relatively high level of 10 U/mL. Combining GADA with other islet-related autoantibodies or HLA class II genotype increased positive predictive value but decreased sensitivity. Conclusions: Our results suggest that latent autoimmune diabetes in adults constitutes a heterogeneous group and that the majority of patients with high GADA titres (≥10 U/mL) will ultimately develop type 1 diabetes while those with low titres include patients with type 1 and type 2 diabetes.