Slowly progressing type 1 diabetes: Persistence of islet cell autoantibodies is related to glibenclamide treatment

Background : Several experimental studies in rats have demonstrated that sulfonylurea treatment increases autoantigen expression in B-cells. This phenomenon may be deleterious for the preservation of residual beta cell function in patients with slowly progressing type 1 diabetes or latent autoimmune diabetes of adult (LADA). Aim/hypothesis:The aim of the present study was to evaluate whether the exclusion of glibenclamide in the treatment of ICA positive type 2 diabetic patients may diminish or halt the humoral autoimmune response against B-cells as well as improve metabolic control and insulin secretion. Subjects and methods : Fourteen type 2 diabetic patients with pancreatic autoimmunity (ICA+ and GABA+) and treated with insulin and glibenclamide (duration of disease 2.0+/-2.2, range 0.1-7 years and age 53+/-12.5, range 36-75 years) were studied. Patients were randomly assigned to two treatment groups, Group 1: insulin monotherapy (n=8, age 53+/-6.4 years) (Exclusion of glibenclamide) and, Group 2: insulin plus glibenclamide (n=6, age 53.5+/-16.9 ) (Unmodified treatment). Both groups were investigated at the beginning of the study and after one year for the following parameters: ICA and anti-GAD65 antibodies, fasting glucose and fasting C-peptide. Results : In group 1, six out of eight patients became ICA negative while all patients in group 2 remained ICA positive (p=0.0097). Fasting glucose concentrations improved in group 1 (4.6+/-2.8) in relation to group 2 (11.5+/-5.5, p=0.0023) after one year of treatment. No differences were found for anti-GAD antibodies and fasting C-Peptide between the groups. Conclusions : These data show that exclusion of glibenclamide in the treatment of ICA+ type 2 diabetic patients partially decreases specific autoimmunity against endocrine pancreatic cells and improves metabolic control. This may reflect decreased expression of B-cell autoantigens suggesting that insulin monotherapy is a better choice for the treatment of LADA.