Slowly Progressing Type 1 Diabetes: Persistence of Islet Cell Autoantibodies is Related to Glibenclamide Treatment

• Published in: Autoimmunity (Chur, Switzerland) Switzerland), 2002-01, Vol.35 (7), p.469-474
• Main Authors: Cabrera-Rode, Eduardo, Perich, Pedro, Diaz-Horta, Oscar, Tiberti, Claudio, Molina, Gisela, Arranz, Celeste, Martin, Juana M., Licea, Manuel, De Leiva, Alberto, Puig-Domingo, Manuel, Dimario, Umberto
• Format: Article
• Language: English
• Subjects: Autoantibodies - drug effects; Autoantibodies - immunology; Biological and medical sciences; Blood Glucose; Body Mass Index; C-Peptide - blood; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - drug therapy; Drug toxicity and drugs side effects treatment; Glibenclamide Therapy; Glutamate Decarboxylase - immunology; Glutamic Acid Decarboxylase Antibodies; Glyburide - pharmacology; Humans; Hypoglycemic Agents - pharmacology; Islet Cell Antibodies; Islets of Langerhans - drug effects; Islets of Langerhans - immunology; Isoenzymes - immunology; Latent Autoimmune Diabetes Of Adult (LADA); Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Slowly Progressing Type 1 Diabetes; Type 2 Diabetes
• ISSN: 0891-6934; 1607-842X
• DOI: 10.1080/0891693021000050574

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 &#45 2.2, range 0.1-7 years and age 53 &#45 12.5, range 36-75 years) were studied. Patients were randomly assigned to two treatment groups, Group 1: insulin monotherapy (n = 8, age 53 &#45 6.4 years) (Exclusion of glibenclamide) and, Group 2: insulin plus glibenclamide (n = 6, age 53.5 &#45 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 &#45 2.8) in relation to group 2 (11.5 &#45 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.